Good morning! It is the last day of July, and thus Day "31" of the Whole30, a strict 30 day plan designed by (the gorgeous) Melissa and Dallas Hartwig with no processed food, no alcohol, no legumes, no grains whatsoever, no white potatoes, no dairy (including butter), no sugar or sugar substitutes (even honey and whatnot).
I don't do diets, by the way. They don't work. And they make you crazy. And yet, in many ways, the Whole30 is unsustainable perfection unless there is a darn good reason.
So why did I do the Whole30? An experiment. And there is scientific validation for elimination diets - it is the gold standard way to determine certain food intolerances. What I admire about Dallas and Melissa is they make that clear - the Whole30 is about health and seeing if you find some positives with a strict month, it is not the rest of your life, it is not about losing weight. It is not a "diet" in that sense.
It was interesting to go forward with the Whole30 when my regular eating pattern was already fairly similar. That way, if there were issues, it would be easy to figure out the exact problems. And there are exactly seven differences between the Whole30 and the way I ate for most the year before the Whole30 (there is a Whole30 meal template that I did try to stick to also, which constitutes another difference, but just in terms of types of food consumed):
1) Rare added sugar (usually honey). By rare I mean rare. A teaspoon of honey in tea every couple of weeks. Honey in a flourless chocolate cake twice in six months. Except chocolate, which was usually a piece of a 85% dark chocolate bar every other day. A bar would usually last a week.
2) Artificial sweeteners (gum and Diet Coke)
3) Cheating (usually gluten in homemade pizza, sometimes Mexican food - but not that often - once a month)
4) High fat dairy - after 3 months of NO dairy at all last year, I added back butter regularly, sometimes yogurt, sometimes cream with berries, sometimes cheese. All told I probably ate high fat dairy not counting butter 3X a week.
5) White rice and white potatoes - these and other starchy carbs (winter squash, sweet potatoes, turnips) once daily - you are supposed to eat starchy carbs like winter squash and sweet potatoes on the Whole30, but not rice and potatoes.
6) Alcohol - 5 glasses of wine a week (I did try to keep it away from 2 hours before bedtime, as even one glass of wine will disturb my sleep if I drink it too close to bedtime)
7) IF ing - prior to Whole30, 24 hours usually on Monday, 16 hours a couple of other times during the week
Things I deliberately didn't change - amount of exercise and amount of starchy carb. I did try to eat Whole30 approved starchy carb in about the same amounts in my meals as I did before Whole30. In all likelihood I did consume more fruit on the Whole30 than before.
As I wrote about a week ago, I did go on vacation to a city with very fine restaurants, which means my Whole30 was not pristine. In addition, ever since having rather extreme morning sickness during my pregnancies, sometimes I still get very nauseated in the mornings, and a half a teaspoon of honey in tea cures it instantly. It's psychosomatic plus my typical lowish blood sugar, I believe. Anyway, I did have honey once, and several cheat meals involving a touch of dairy on the trip - fish with a very sparse crust of parmesan and (literally) a drizzle of buttermilk dressing on some romaine, for example. Which is fine, because it means that my Whole30 was more like my real life and the number of "differences" up there drops to 5 - forget 1) and 3).
So, what were the results and what was it like? I've lost 7 pounds - five of that happened in the first 10 days (I think - that is when the dress size loss happened). I feel energetic. I'm sleeping through the night better, but it is much harder to get to sleep - I used to collapse around 9 or 9:30 and wake up at 2-3am for a few hours. Now I can't generally get to sleep before 11, but I don't tend to wake up until 5am.
So fairly dramatic. I started out with a BMI of 23.2 and now it is 21.8. I'm wearing size 4-6 currently, which is typically a small. My clothes from 10 years ago (which was usually 6 or 8 or 10 or medium but sizes have ballooned in the intervening years) fit or are a little loose.
And I'm pretty convinced the major causative factor is the high fat dairy - because I had done little experiments in the past year removing artificial sweeteners or alcohol for a couple of weeks, and my weight was rock steady. And I don't see a qualitative difference between a similar amount of sweet potato and a regular potato or rice with respect to sudden weight loss that happens in a week. Also, there is a family history (two first degree relatives) with dairy intolerance so I should just buck up and cut it out (both family members can tolerate butter). But it could also be the chocolate or the insidious cheat creep that can happen.
What do I plan from here? I'm going to experiment with adding back in rice and white potatoes - they are cheap, convenient, and the kids love them. I will not add back artificial sweeteners. Honestly my strongest motivation for the Whole30 was not weight loss so much as kicking the Diet Coke habit that had crept back in over the last 6 months. I will drink wine, but will tend keep it more to special occasions, parties, meals out, etc. instead of "Woo it's friday night!" Heh. And life is too short not to have chocolate - maybe it won't be a bar a week. Chocolate keeps well. Chocolate is pretty much awesome in every way.
Oh, and IFing. I like the health data behind the intermittent fast, and I did like the "buzz" I got in the afternoon (probably cortisol, however), and I like the convenience. I didn't IF on the Whole30 because I was hungry, and I believe in eating when one is hungry. I'm guessing I will add it back in but not as aggressively as before. I hadn't realized how IF added stress in some ways until I stopped doing it.
So life after the Whole30 will be mostly similar to life on the Whole30, with more chocolate and alcohol. I'll do a more careful experiment with rice and potatoes. I'm very glad I decided to do the Whole30, even though I wasn't perfect and I already knew a lot about myself and diet from the "paleo" experiment of the previous year - I still learned a great deal. Elimination diets can be very useful for a variety of reasons.
Once again I am traveling this week - flurry of work to do then leaving Thursday morning for the Ancestral Health Symposium. This will likely be the last blog post (save, perhaps, some quick uploads to Psychology Today) until then.
Sunday, July 31, 2011
Thursday, July 28, 2011
The Incredible Shrinking Human Brain
Thanks to Tim who sent me the link to this Wall Street Journal article:
Brain Shrinkage: It's Only Human
Yup. Many parts wither as we age, our brains among them. Octogenarians are liable to have brains 15% smaller than Justin Bieber's brain. Imagine that! Humans it seems are unique among primates in that we are longest-lived with the largest brains, and are also susceptible to neuropathology in the late stages of life, such as dementia.
There are several types of dementia, but even normal human aging is characterized by neural deterioration and cognitive impairment to some extent. Various pathologies are common - amyloid beta deposits, neuron trees dying off, reduced synapse numbers, loss of specific receptors… these seem to occur specifically in areas that are part of learning, memory, and executive function. Some of these same changes occur in other primate species whose members (rarely) get, well, senile. There have been case reports of elderly gorillas or chimps with Alzheimer's like plaques and tangles. So for a long time, scientists apparently assumed that as a large extended family, our big primate brains kinda sputter out at the end, especially humans, with the biggest and longest-lived brain.
The (free for now) WSJ article reports on a new study done by Sherwood et al in PNAS, called Aging of the cerebral cortex differs between humans and chimpanzees.
Sherwood and his compatriots had the bright idea to get brain MRIs of a bunch of humans (87) and a bunch of chimps (69) spanning a wide age range - in chimps, ages 10-51, in humans, ages 22-88. And, sure enough, among the humans, there was significant shrinkage in every area of the brain measured. But, surprisingly, no significant shrinkage among the chimps. Boom. Humans are very vulnerable to dementia (except, of course, the famous Kitavans - and I will get back to that later). Chimps don't seem to be.
Now there are a few wrinkles to understand here. The age ranges of both humans and chimps were chosen for the study by how long humans and chimps are expected to live (if they don't get killed in an accident or illness) in the wild - about 45 for chimps, and into the 80s for humans. But, when the human data for this study were parsed out by age, it seems that all the major shrinkage occurred in the 7th and 8th decades of life, not before, and other human studies show there is minimal shrinking between ages 25 and 50, with accelerated shrinking thereafter. This age is well above the age of any known chimpanzee in the wild. One post-mortem study of captive chimps had a very minimal decline of brain size with age - the oldest captive chimp was 59. Another study involving macaque monkeys (some 30 million years removed in lineage from humans, I believe) also showed no brain degeneration with age.
So… it would appear that humans are relatively unique in that our brains self destruct into a smokey inflammatory puddle of shrunken senility. And we can't just say the chimps didn't get as old as we do - relatively speaking - they do. Chimps start to slow down and become more physically frail with worn teeth in the 30s, though the females are fertile until nearly the end of the normal chimp lifespan. Humans have a longer childhood and are generally still quite robust through the 30s and 40s, and women obviously hit menopause around age 50, followed by (generally) 2-3 more decades in a normal lifespan. It is clear, then, that humans age more slowly than chimps.
Now, evolutionarily speaking, the authors of this paper throw out the grandmother hypothesis - humans clearly live long because there was a survival advantage among the grandchildren who had grandmothers around collecting food and passing on cultural knowledge. But does that longevity have a cost unknown to other, grandmother-less primates?
As we well know, dementing brains have a build-up of protein aggregates and rely on the shoddy energy production of poorly functioning, reactive oxygen species-producing damaged mitochondria. As we get older, our oxidative stress protection gene expression is upregulated - until I suppose it can be upregulated no more, and the cost of being a human with our big, energy hogging brains for so long is too high, and everything goes to hell in a hand basket.
The sticking point I have with this study? Well, none of the subjects were "wild-type." All the chimps were captives from the Yerkes National Primate Research Center in Atlanta. The humans were volunteers, all right-handed, about equal numbers men and women, and all were healthy, with no psychiatric disorders, heart disease, hypertension, or diabetes. I'm fairly convinced that Staffan Lindeberg did not take an MRI machine with him to Papua New Guinea. So I don't know if the dementia-free Kitavans in the last century had shrinking brains.
So is dementia a human thing, the direct cost of being the brightest and longest-lived of all primates, design specs maxed out at a biochemical level? Or is it a modern, industrial human thing, wrought from micronutrient deficiencies, infection, chronic hyperglycemia, and mucking around with our capability to produce cholesterol? What do they feed those chimps in the Yerkes center, anyway?
I know what I think - what makes sense is that we aren't meant to become senile and a long-term survival burden as we age. Okay, so maybe our big glorious brains are derived in part from sexual selection - thus an expensive ornament like a peacock's tail, meant to woo women, with a survival cost and not just survival benefit. And yet… why evolve grandmothers just to have them get senile? The grandmother hypothesis would be completely backwards if our brains are just designed to slowly sputter out. I don't have the proof - but my speculation is that true wild-type humans, even the very old, have robust brains too, like old chimps or gorillas.
A couple of other things before we go - today my podcast with Jimmy Moore came out - you can listen to it here (I remember saying I eat 18 eggs a week, which isn't true - my family eats about 18 eggs a week. I eat about 12 of those :-) ) In any case it was a lot of fun talking to Jimmy. He has an infectious enthusiasm.
And I have a couple new articles up at Psychology Today. Please give them a click!
Sleep, Hyperactivity, and Behavior in Children
A Case of Scratchy Mice
Brain Shrinkage: It's Only Human
Yup. Many parts wither as we age, our brains among them. Octogenarians are liable to have brains 15% smaller than Justin Bieber's brain. Imagine that! Humans it seems are unique among primates in that we are longest-lived with the largest brains, and are also susceptible to neuropathology in the late stages of life, such as dementia.
There are several types of dementia, but even normal human aging is characterized by neural deterioration and cognitive impairment to some extent. Various pathologies are common - amyloid beta deposits, neuron trees dying off, reduced synapse numbers, loss of specific receptors… these seem to occur specifically in areas that are part of learning, memory, and executive function. Some of these same changes occur in other primate species whose members (rarely) get, well, senile. There have been case reports of elderly gorillas or chimps with Alzheimer's like plaques and tangles. So for a long time, scientists apparently assumed that as a large extended family, our big primate brains kinda sputter out at the end, especially humans, with the biggest and longest-lived brain.
The (free for now) WSJ article reports on a new study done by Sherwood et al in PNAS, called Aging of the cerebral cortex differs between humans and chimpanzees.
 |
| Flickr Creative Commons |
Now there are a few wrinkles to understand here. The age ranges of both humans and chimps were chosen for the study by how long humans and chimps are expected to live (if they don't get killed in an accident or illness) in the wild - about 45 for chimps, and into the 80s for humans. But, when the human data for this study were parsed out by age, it seems that all the major shrinkage occurred in the 7th and 8th decades of life, not before, and other human studies show there is minimal shrinking between ages 25 and 50, with accelerated shrinking thereafter. This age is well above the age of any known chimpanzee in the wild. One post-mortem study of captive chimps had a very minimal decline of brain size with age - the oldest captive chimp was 59. Another study involving macaque monkeys (some 30 million years removed in lineage from humans, I believe) also showed no brain degeneration with age.
So… it would appear that humans are relatively unique in that our brains self destruct into a smokey inflammatory puddle of shrunken senility. And we can't just say the chimps didn't get as old as we do - relatively speaking - they do. Chimps start to slow down and become more physically frail with worn teeth in the 30s, though the females are fertile until nearly the end of the normal chimp lifespan. Humans have a longer childhood and are generally still quite robust through the 30s and 40s, and women obviously hit menopause around age 50, followed by (generally) 2-3 more decades in a normal lifespan. It is clear, then, that humans age more slowly than chimps.
Now, evolutionarily speaking, the authors of this paper throw out the grandmother hypothesis - humans clearly live long because there was a survival advantage among the grandchildren who had grandmothers around collecting food and passing on cultural knowledge. But does that longevity have a cost unknown to other, grandmother-less primates?
As we well know, dementing brains have a build-up of protein aggregates and rely on the shoddy energy production of poorly functioning, reactive oxygen species-producing damaged mitochondria. As we get older, our oxidative stress protection gene expression is upregulated - until I suppose it can be upregulated no more, and the cost of being a human with our big, energy hogging brains for so long is too high, and everything goes to hell in a hand basket.
The sticking point I have with this study? Well, none of the subjects were "wild-type." All the chimps were captives from the Yerkes National Primate Research Center in Atlanta. The humans were volunteers, all right-handed, about equal numbers men and women, and all were healthy, with no psychiatric disorders, heart disease, hypertension, or diabetes. I'm fairly convinced that Staffan Lindeberg did not take an MRI machine with him to Papua New Guinea. So I don't know if the dementia-free Kitavans in the last century had shrinking brains.
So is dementia a human thing, the direct cost of being the brightest and longest-lived of all primates, design specs maxed out at a biochemical level? Or is it a modern, industrial human thing, wrought from micronutrient deficiencies, infection, chronic hyperglycemia, and mucking around with our capability to produce cholesterol? What do they feed those chimps in the Yerkes center, anyway?
I know what I think - what makes sense is that we aren't meant to become senile and a long-term survival burden as we age. Okay, so maybe our big glorious brains are derived in part from sexual selection - thus an expensive ornament like a peacock's tail, meant to woo women, with a survival cost and not just survival benefit. And yet… why evolve grandmothers just to have them get senile? The grandmother hypothesis would be completely backwards if our brains are just designed to slowly sputter out. I don't have the proof - but my speculation is that true wild-type humans, even the very old, have robust brains too, like old chimps or gorillas.
A couple of other things before we go - today my podcast with Jimmy Moore came out - you can listen to it here (I remember saying I eat 18 eggs a week, which isn't true - my family eats about 18 eggs a week. I eat about 12 of those :-) ) In any case it was a lot of fun talking to Jimmy. He has an infectious enthusiasm.
And I have a couple new articles up at Psychology Today. Please give them a click!
Sleep, Hyperactivity, and Behavior in Children
A Case of Scratchy Mice
Tuesday, July 26, 2011
Fat and Happy
Yesterday, Julianne and Stabby were tweeting about this new paper, which Jamie was kind enough to send along to me later - Fatty acid-induced gut brain signaling attenuates neural and behavioral effects of sad emotions in humans.
Now that title has three words I like rather a lot - "gut," "brain," and "humans." It begins to feel a little lonely sifting through the rodent literature, wondering what could be applicable to you and me. I wonder if you feed a rat a hot dog, would it be just as bad as getting a mouse to smoke a cigarette?
But back to the humans - 12 non-obese subjects agreed for some reason to have nasogastric tubes slithered down into their gullets before the subjects crawled into a very small but expensive tube to have functional MRIs done. The subjects were given either a saline infusion or an infusion of dodecanoic acid (que? Also known as lauric acid, or the main component of coconut oil. Interestinger and interestinger!) During this procedure, the subjects also had "sad" or "neutral" classical music piped into the tube, and were shown sad faces or neutral facial expressions matching the music. They were also asked to fill out scales rating fullness, nausea, and hunger, as well as indicating mood on a scale of 1 (sad) to 5 (neutral) to 9 (happy). All of the subjects went through all variations - saline + sad music, fat + sad music, saline + neutral music, and fat + neutral music in 4 different scans on 4 different days, but in randomized order, and always after a 12 hour fast.
The results? Well, hunger increased significantly with the sad music and sad faces. The lauric acid decreased both hunger and the sad feelings significantly more than saline. Hunger did not increase with neutral music and faces, and the difference in hunger between the fat and saline groups listening to the neutral music was non-significant, suggesting that fat sluiced down into the stomach was indeed the factor that attenuated the sad/hunger connection. In addition, the "sad" subjects experienced less sensation of fullness after the fat or saline infusion than the "neutral" subjects.
The mechanism thought to explain the emotion/hunger connection is in the reward system of the brain. This is thought to be the case both in healthy volunteers, and in people with eating disorders or obesity.
The fMRI data showed that certain areas of the brain associated with mood and the reward system* were activated differently based on the different stimuli. Under neutral emotional conditions, fatty acid infusion activated the metabolism in these regions more than the saline infusion. Sad emotion also activated the metabolism in these regions, and the activation decreased upon fatty acid infusion compared to saline. It appears, then, that fat activated the emotional centers of the brain, as did sadness, but that fat seemed to cool off the sadness (which was reflected in the mood scores of the participants). The effect of fat on sadness was two-fold decrease compared to saline. This effect is about the same as the change in mood scores in those treated with antidepressants.
The authors note that previous studies (which are hard to compare, as they involved eating food and all the associated smells, textures, and pleasures associated with that) typically rated mood and carbohydrate response, and these studies were also done over the course of a few weeks (the fat or saline was infused over the course of 2 minutes in this experiment).
So - what do we learn? Does fat make us happy? Well, what do you want to eat when you are feeling blue - an apple or a chocolate bar? The editorial for the study we're discussing is quite interesting (but not free without academic access). Another independent study done in mice showed that increasing stress resulted in increased ghrelin secretion, increased corticosteroid secretion, and increased fat-seeking behavior (for the typical rat high fat diet pellets.) The authors note that young people in a longitudinal study from New Zealand who have a major depressive episode during youth have a 2.3 fold increase in the incidence of obesity in adulthood. So there is a presumed mechanism - stress causes us to want to eat, and eating alleviates stress. However, 40% of people report increased appetite during stress, and 40% report decreased appetite. And certainly other adipose mass control mechanisms should eventually compensate - is it our stressful modern lives, or a combination of our stressful lives plus our poisonous modern foods?
There are many more questions raised than answered by the human study - what is the actual mechanism? The editorial discusses the possible action of the gastric hormones ghrelin or CCK**, which are both known to have emotional and brain effects. And what would happen with infusions of protein or carbohydrate, or in other emotional states, such as aggression, happiness, or arousal? Would there be any difference in subjects who are obese or have eating disorders? Women vs. men, women in different stages of the menstrual cycle? If I had an fMRI, a few hundred nasogastric tubes, and a bunch of willing subjects, I would crank out papers as fast as I crank out blog posts with this experimental design. Hopefully this article is not the last we hear from these researchers!
* specifically the medulla/pons, midbrain, hypothalamus, thalamus, caudate head, putamen, cerebellum, right hippocampus, left pACC (pre- genual anterior cingulate cortex), MCC, and PCC.
** From the editorial: "Since the fatty acid solution was administered directly to the stomach, likely mechanisms include the peptide hormone ghrelin, which is produced predominantly by distinct ghrelin-producing cells in the stomach and other parts of the gastrointestinal tract, as well as stimulation of parasympathetic terminals located in the stomach. The latter would implicate a function for the gut peptide cholecystokinin (CCK), which has previously been shown to have a crucial role in mediating the effects of intragastric fatty acid solutions on brain activity. Additional support for a role for CCK is provided by the fact that phylogenetically, receptors for CCK are known not only for their role in digestion, but also for roles in memory function and learning and in modulation of panic and anxiety."
Now that title has three words I like rather a lot - "gut," "brain," and "humans." It begins to feel a little lonely sifting through the rodent literature, wondering what could be applicable to you and me. I wonder if you feed a rat a hot dog, would it be just as bad as getting a mouse to smoke a cigarette?
But back to the humans - 12 non-obese subjects agreed for some reason to have nasogastric tubes slithered down into their gullets before the subjects crawled into a very small but expensive tube to have functional MRIs done. The subjects were given either a saline infusion or an infusion of dodecanoic acid (que? Also known as lauric acid, or the main component of coconut oil. Interestinger and interestinger!) During this procedure, the subjects also had "sad" or "neutral" classical music piped into the tube, and were shown sad faces or neutral facial expressions matching the music. They were also asked to fill out scales rating fullness, nausea, and hunger, as well as indicating mood on a scale of 1 (sad) to 5 (neutral) to 9 (happy). All of the subjects went through all variations - saline + sad music, fat + sad music, saline + neutral music, and fat + neutral music in 4 different scans on 4 different days, but in randomized order, and always after a 12 hour fast.
The results? Well, hunger increased significantly with the sad music and sad faces. The lauric acid decreased both hunger and the sad feelings significantly more than saline. Hunger did not increase with neutral music and faces, and the difference in hunger between the fat and saline groups listening to the neutral music was non-significant, suggesting that fat sluiced down into the stomach was indeed the factor that attenuated the sad/hunger connection. In addition, the "sad" subjects experienced less sensation of fullness after the fat or saline infusion than the "neutral" subjects.
The mechanism thought to explain the emotion/hunger connection is in the reward system of the brain. This is thought to be the case both in healthy volunteers, and in people with eating disorders or obesity.
The fMRI data showed that certain areas of the brain associated with mood and the reward system* were activated differently based on the different stimuli. Under neutral emotional conditions, fatty acid infusion activated the metabolism in these regions more than the saline infusion. Sad emotion also activated the metabolism in these regions, and the activation decreased upon fatty acid infusion compared to saline. It appears, then, that fat activated the emotional centers of the brain, as did sadness, but that fat seemed to cool off the sadness (which was reflected in the mood scores of the participants). The effect of fat on sadness was two-fold decrease compared to saline. This effect is about the same as the change in mood scores in those treated with antidepressants.
The authors note that previous studies (which are hard to compare, as they involved eating food and all the associated smells, textures, and pleasures associated with that) typically rated mood and carbohydrate response, and these studies were also done over the course of a few weeks (the fat or saline was infused over the course of 2 minutes in this experiment).
So - what do we learn? Does fat make us happy? Well, what do you want to eat when you are feeling blue - an apple or a chocolate bar? The editorial for the study we're discussing is quite interesting (but not free without academic access). Another independent study done in mice showed that increasing stress resulted in increased ghrelin secretion, increased corticosteroid secretion, and increased fat-seeking behavior (for the typical rat high fat diet pellets.) The authors note that young people in a longitudinal study from New Zealand who have a major depressive episode during youth have a 2.3 fold increase in the incidence of obesity in adulthood. So there is a presumed mechanism - stress causes us to want to eat, and eating alleviates stress. However, 40% of people report increased appetite during stress, and 40% report decreased appetite. And certainly other adipose mass control mechanisms should eventually compensate - is it our stressful modern lives, or a combination of our stressful lives plus our poisonous modern foods?
There are many more questions raised than answered by the human study - what is the actual mechanism? The editorial discusses the possible action of the gastric hormones ghrelin or CCK**, which are both known to have emotional and brain effects. And what would happen with infusions of protein or carbohydrate, or in other emotional states, such as aggression, happiness, or arousal? Would there be any difference in subjects who are obese or have eating disorders? Women vs. men, women in different stages of the menstrual cycle? If I had an fMRI, a few hundred nasogastric tubes, and a bunch of willing subjects, I would crank out papers as fast as I crank out blog posts with this experimental design. Hopefully this article is not the last we hear from these researchers!
* specifically the medulla/pons, midbrain, hypothalamus, thalamus, caudate head, putamen, cerebellum, right hippocampus, left pACC (pre- genual anterior cingulate cortex), MCC, and PCC.
** From the editorial: "Since the fatty acid solution was administered directly to the stomach, likely mechanisms include the peptide hormone ghrelin, which is produced predominantly by distinct ghrelin-producing cells in the stomach and other parts of the gastrointestinal tract, as well as stimulation of parasympathetic terminals located in the stomach. The latter would implicate a function for the gut peptide cholecystokinin (CCK), which has previously been shown to have a crucial role in mediating the effects of intragastric fatty acid solutions on brain activity. Additional support for a role for CCK is provided by the fact that phylogenetically, receptors for CCK are known not only for their role in digestion, but also for roles in memory function and learning and in modulation of panic and anxiety."
Sunday, July 24, 2011
Bipolar Case Study on the Web and Whole30 on Vacation
Greetings! I'm back in town. The tomatoes, flowers, cats, and fish survived thanks to our very able house sitter, and we're all in good spirits despite air travel with small children (and no, we were not fondled or irradiated extra times in security).
Here's a new song I rather like - Whirring by The Joy Formidable (right click in new tab).
We went to Santa Fe, a lovely New Mexico mountain town and as far as I know, at 7200 feet or thereabouts, the highest state capital in the United States. Though it is not Disney World or anything, we were able to keep the kids well occupied with the Santa Fe Children's Museum, Grandparents, daily walks through old town to the plaza (they have live music there every day), and a couple of cool parks around town. These parks had lots of spiced up natural spaces to make it fun for the kids - large sandboxes housed next to tree trunk amphitheaters, stacks of rocks for climbing, slides built into a hillside, tunnels, etc.
The Whole30 did not survive intact, however, I was mostly very compliant with the rules. But the Whole30 is not about mostly, it is about a strict 30 days of no cheating for a couple of good reasons - 1) it's meant to be an elimination diet to help establish any issues with dairy or gluten or whatnot, and it is important to be quite strict on an elimination diet 2) it's about establishing your supremacy as a human with a will over cravings and food issues.
So what happened? Well, it turns out that in my normal environment is is relatively easy for me to say no to temptation Who cares if I sip mineral water instead of wine at this backyard gathering or that one, or skip ice cream at the kid's birthday party? There will be another backyard gathering next month, and it's not as if the ice cream and cake and pizza at birthday parties are particularly good anyway. Even when I'm not doing a Whole30, I tend to skip that stuff.
But in Santa Fe, a couple of circumstances came up - food I'm not able to get well made where I live or within a 1000 miles of where I live, and eating at very good restaurants with the chef sort of standing over me. So a couple of banned foods slipped through - a Whole20 + a Whole10 do not make a Whole30, but I think I'll try to put together 30 days in September instead, when no vacations are planned. For the most part I stuck to the rules, however (2 meals in 24 over vacation had small infractions, not counting the vegetable oil the fajitas were probably cooked in) - though it was difficult finding safe starches when eating out so much (around here most restaurants have sweet potato as an option - not so popular in the Mexican food arena, I'm seeing). I ended up eating quite a few bananas over the week. And when I was out of my normal environment for such a long period of time, it became more clear just how different strict paleo is from what most people eat all the time.
Now onto something perhaps more interesting - an article online by Michael Ellsberg - How I Overcame Bipolar II and Saved My Own Life. This article was emailed to me and pointed out to me on twitter, and it is a detailed, heartfelt, and well-written account of how some dietary changes (mostly eliminating sugar, refined carbohydrates, coffee, and alcohol, and originally by adding a complete multivitamin/multimineral) dramatically reduced symptoms of bipolar disorder (you'll notice that when he added together bunches of serotonin-boosting supplements he ended up with similar side effects to being on an SSRI). It is a case study, of course, but I find case studies very intriguing and useful when they involve simple interventions that are unlikely to cause harm (such as eliminating sugar). Even I don't think even very strict dietary and lifestyle interventions will cure everyone of everything. I've always felt the major possibilities of nutritional interventions for something as complex as mental illness would be to possibly ameliorate some symptoms and in prevention of a lot of chronic Western disease in general. And when they are dietary and lifestyle interventions that would lead to better health overall, it seems to fit that "do no harm" bill very nicely indeed.
A huge pile of research papers and common sense tell us that maximizing "real food," minimizing food toxins, and eliminating micronutrient deficiencies are vital for the body to work well, including the brain. It does not surprise me that some people will have huge mental health benefits from following that sort of plan - and it shouldn't surprise doctors or neuroscientists either. To me the most striking thing about the article are the number of critical comments (despite his disclaimer) telling Mr. Ellsberg he is being irresponsible for telling his own story.
There are some things, it is fair to say, that we don't want to believe.
Here's a new song I rather like - Whirring by The Joy Formidable (right click in new tab).
We went to Santa Fe, a lovely New Mexico mountain town and as far as I know, at 7200 feet or thereabouts, the highest state capital in the United States. Though it is not Disney World or anything, we were able to keep the kids well occupied with the Santa Fe Children's Museum, Grandparents, daily walks through old town to the plaza (they have live music there every day), and a couple of cool parks around town. These parks had lots of spiced up natural spaces to make it fun for the kids - large sandboxes housed next to tree trunk amphitheaters, stacks of rocks for climbing, slides built into a hillside, tunnels, etc.
So what happened? Well, it turns out that in my normal environment is is relatively easy for me to say no to temptation Who cares if I sip mineral water instead of wine at this backyard gathering or that one, or skip ice cream at the kid's birthday party? There will be another backyard gathering next month, and it's not as if the ice cream and cake and pizza at birthday parties are particularly good anyway. Even when I'm not doing a Whole30, I tend to skip that stuff.
But in Santa Fe, a couple of circumstances came up - food I'm not able to get well made where I live or within a 1000 miles of where I live, and eating at very good restaurants with the chef sort of standing over me. So a couple of banned foods slipped through - a Whole20 + a Whole10 do not make a Whole30, but I think I'll try to put together 30 days in September instead, when no vacations are planned. For the most part I stuck to the rules, however (2 meals in 24 over vacation had small infractions, not counting the vegetable oil the fajitas were probably cooked in) - though it was difficult finding safe starches when eating out so much (around here most restaurants have sweet potato as an option - not so popular in the Mexican food arena, I'm seeing). I ended up eating quite a few bananas over the week. And when I was out of my normal environment for such a long period of time, it became more clear just how different strict paleo is from what most people eat all the time.
Now onto something perhaps more interesting - an article online by Michael Ellsberg - How I Overcame Bipolar II and Saved My Own Life. This article was emailed to me and pointed out to me on twitter, and it is a detailed, heartfelt, and well-written account of how some dietary changes (mostly eliminating sugar, refined carbohydrates, coffee, and alcohol, and originally by adding a complete multivitamin/multimineral) dramatically reduced symptoms of bipolar disorder (you'll notice that when he added together bunches of serotonin-boosting supplements he ended up with similar side effects to being on an SSRI). It is a case study, of course, but I find case studies very intriguing and useful when they involve simple interventions that are unlikely to cause harm (such as eliminating sugar). Even I don't think even very strict dietary and lifestyle interventions will cure everyone of everything. I've always felt the major possibilities of nutritional interventions for something as complex as mental illness would be to possibly ameliorate some symptoms and in prevention of a lot of chronic Western disease in general. And when they are dietary and lifestyle interventions that would lead to better health overall, it seems to fit that "do no harm" bill very nicely indeed.
A huge pile of research papers and common sense tell us that maximizing "real food," minimizing food toxins, and eliminating micronutrient deficiencies are vital for the body to work well, including the brain. It does not surprise me that some people will have huge mental health benefits from following that sort of plan - and it shouldn't surprise doctors or neuroscientists either. To me the most striking thing about the article are the number of critical comments (despite his disclaimer) telling Mr. Ellsberg he is being irresponsible for telling his own story.
There are some things, it is fair to say, that we don't want to believe.
Thursday, July 14, 2011
Groovy Probiotics
Music to start - classical again, let's go Russian with Rimsky-Korsakov and Procession of the Nobles (right click in new tab).
News next - This post will most likely be the last one for a week or more, though I'm updating a couple of older posts for Psychology Today and may post a link tomorrow. I'm on vacation. Whew.
Update on the July Whole30 - finishing up Day 14, and the main thing I'm finding is that it is difficult to eat quite enough. I've lost a dress size (and I'm not trying to restrict calories), but can be a bit cranky before meals, and after the first week I've not been particularly hungry. Though I love the freedom and convenience of rather frequent intermittent fasting, it has also been nice to simply eat three meals a day and throw in an extra banana, some berries, or a few macadamia nuts for snacks. No "cheating" except for a half teaspoon of honey in tea on Monday morning (I had a good reason for it). All cravings for chocolate and Diet Coke were pretty much done by the end of the third or fourth day. The honey ingestion didn't reawaken any of that.
Vacation will up the ante. It will be difficult to be eating out at restaurants all the time and be as sure as one ought to be in the Whole30 about ingredients. We'll see how it goes. I'm not going to throw in the towel if I realize something is screwed up, and will likely just try to order steak as much as possible. Veggies may be difficult as they are usually cooked with butter or covered with soybean-oil based salad dressing.
Now the paper! This one is on the hypothetical side - all tell, no show, but rather fun. I believe Chris Kresser tweeted it to my attention, or it could have been Dallas and Melissa. Both of them sent me probiotics papers so thanks to both!
Ahem. Probiotics function mechanistically as delivery vehicles for neuroactive compounds: Microbial endocrinology in the design and use of probiotics.
The down-low is that probiotics are thought to modulate the production of inflammatory particles (cytokines), affect the adhesion of pathogens to the gut mucosa, and other groovy things. However, no one really knows how they do what it is that they do. There are now several studies with intriguing evidence that probiotics can affect the brain (one of which I wrote about earlier this week). One study even showed anxiety reduction in human volunteers (and mice) with administration of Lactobacillus helveticus and B. longum. Again, since disorders that affect the gastrointestinal tract seem to co-exist quite frequently with anxiety, depression, and other mood disorders, probiotics and gut health may have "profound clinical implications."
There is a great deal we don't know. Many of the organisms can't be cultured. It's difficult to study the secret life of the wee beasties while the host is walking around doing the day to day. There are zillions of varieties of beasties, and typically the probiotics used for studies depend on what company is supplying them rather than a more specific rationale or knowledge of the effects of each species.
So what, exactly, do we know? As far back as 1929 it was discovered that human carriers of certain Clostridium species who were given epinephrine to treat hives died suddenly of gas gangrene (oops). For 60 years, it was thought the epinephrine somehow suppressed the immune system, leading to the sudden fulminant infection. In the early 1990s, however, it was found that yes, indeed, gut bacteria could respond directly to human neurochemicals (such as epinephrine). It has been further proven (with the flurry of recent papers) that the communication between the beasties and the brain is a two way street. Neurochemicals are highly conserved in evolution - bacteria, plants, insects, and fish all produce forms of the neurochemicals called the catecholemines. Thus it makes sense that bacteria in our gut can communicate directly with using, to some extent, the same "language" as our mammalian brains.
Lactobacillus and Bifidobacterium species are known to produce GABA. Escherichia, Bacillus, and Saccharomyces produce norepinephrine. Candida, Streptococcus, Escherichia, and Enterococcus produce serotonin. Bacillus and Serratia produce dopamine, and Lactobacillus species produce acetylcholine. That's pretty much the entire hit parade of major neurotransmitters (there's histamine and glutamate and a few others - and histamine is known to be produced by some bacteria that infect shellfish, for example, causing food poisoning).
The most interesting case here is GABA, the major inhibitory neurotransmitter in the nervous system (it chills things out) - and there are whopping amounts made by the bacteria in fermented foods, and is also found in yogurt and typical probiotic capsules. GABA also turns out to be anti-inflammatory in the gut itself, decreasing the release of inflammatory cytokines. Thus there is a plausible mechanism by which certain probiotics could decrease inflammation and aid symptoms of conditions such as IBD or IBS, and, considering the vagus nerve and all it's tendrils in the gut, have direct communication via the neurotransmitter GABA to the brain.
The author of the paper outlines some straightforward methods by which the individual effects of the probiotic species could be systematically characterized and studied. He has developed a framework for the promising new field of microbial neuroendocrinology. Of course his interest is along the lines of mining microbes for human use - it seems to me our ancestors and their fermented traditions have been mining microbes for these uses for some time, without all the species typing and science.
News next - This post will most likely be the last one for a week or more, though I'm updating a couple of older posts for Psychology Today and may post a link tomorrow. I'm on vacation. Whew.
Update on the July Whole30 - finishing up Day 14, and the main thing I'm finding is that it is difficult to eat quite enough. I've lost a dress size (and I'm not trying to restrict calories), but can be a bit cranky before meals, and after the first week I've not been particularly hungry. Though I love the freedom and convenience of rather frequent intermittent fasting, it has also been nice to simply eat three meals a day and throw in an extra banana, some berries, or a few macadamia nuts for snacks. No "cheating" except for a half teaspoon of honey in tea on Monday morning (I had a good reason for it). All cravings for chocolate and Diet Coke were pretty much done by the end of the third or fourth day. The honey ingestion didn't reawaken any of that.
Vacation will up the ante. It will be difficult to be eating out at restaurants all the time and be as sure as one ought to be in the Whole30 about ingredients. We'll see how it goes. I'm not going to throw in the towel if I realize something is screwed up, and will likely just try to order steak as much as possible. Veggies may be difficult as they are usually cooked with butter or covered with soybean-oil based salad dressing.
Now the paper! This one is on the hypothetical side - all tell, no show, but rather fun. I believe Chris Kresser tweeted it to my attention, or it could have been Dallas and Melissa. Both of them sent me probiotics papers so thanks to both!
Ahem. Probiotics function mechanistically as delivery vehicles for neuroactive compounds: Microbial endocrinology in the design and use of probiotics.
The down-low is that probiotics are thought to modulate the production of inflammatory particles (cytokines), affect the adhesion of pathogens to the gut mucosa, and other groovy things. However, no one really knows how they do what it is that they do. There are now several studies with intriguing evidence that probiotics can affect the brain (one of which I wrote about earlier this week). One study even showed anxiety reduction in human volunteers (and mice) with administration of Lactobacillus helveticus and B. longum. Again, since disorders that affect the gastrointestinal tract seem to co-exist quite frequently with anxiety, depression, and other mood disorders, probiotics and gut health may have "profound clinical implications."
There is a great deal we don't know. Many of the organisms can't be cultured. It's difficult to study the secret life of the wee beasties while the host is walking around doing the day to day. There are zillions of varieties of beasties, and typically the probiotics used for studies depend on what company is supplying them rather than a more specific rationale or knowledge of the effects of each species.
So what, exactly, do we know? As far back as 1929 it was discovered that human carriers of certain Clostridium species who were given epinephrine to treat hives died suddenly of gas gangrene (oops). For 60 years, it was thought the epinephrine somehow suppressed the immune system, leading to the sudden fulminant infection. In the early 1990s, however, it was found that yes, indeed, gut bacteria could respond directly to human neurochemicals (such as epinephrine). It has been further proven (with the flurry of recent papers) that the communication between the beasties and the brain is a two way street. Neurochemicals are highly conserved in evolution - bacteria, plants, insects, and fish all produce forms of the neurochemicals called the catecholemines. Thus it makes sense that bacteria in our gut can communicate directly with using, to some extent, the same "language" as our mammalian brains.
Lactobacillus and Bifidobacterium species are known to produce GABA. Escherichia, Bacillus, and Saccharomyces produce norepinephrine. Candida, Streptococcus, Escherichia, and Enterococcus produce serotonin. Bacillus and Serratia produce dopamine, and Lactobacillus species produce acetylcholine. That's pretty much the entire hit parade of major neurotransmitters (there's histamine and glutamate and a few others - and histamine is known to be produced by some bacteria that infect shellfish, for example, causing food poisoning).
The most interesting case here is GABA, the major inhibitory neurotransmitter in the nervous system (it chills things out) - and there are whopping amounts made by the bacteria in fermented foods, and is also found in yogurt and typical probiotic capsules. GABA also turns out to be anti-inflammatory in the gut itself, decreasing the release of inflammatory cytokines. Thus there is a plausible mechanism by which certain probiotics could decrease inflammation and aid symptoms of conditions such as IBD or IBS, and, considering the vagus nerve and all it's tendrils in the gut, have direct communication via the neurotransmitter GABA to the brain.
The author of the paper outlines some straightforward methods by which the individual effects of the probiotic species could be systematically characterized and studied. He has developed a framework for the promising new field of microbial neuroendocrinology. Of course his interest is along the lines of mining microbes for human use - it seems to me our ancestors and their fermented traditions have been mining microbes for these uses for some time, without all the species typing and science.
Tuesday, July 12, 2011
Wheat, Rice, and Children's Brains
There is another post-worthy probiotics paper on the hopper, but before that I wanted to cover an article called Breakfast Staple Types Affect Brain Gray Matter Volume and Cognitive Function in Healthy Children (freely available on PLoS one). I like some parts of this paper, though it is observational in nature, so keep that in mind.
As we all know, our big old brains develop not only prenatally, but also throughout childhood and adolescence. In children, several studies have been done showing nourishing breakfasts help cognitive performance compared to skipping breakfast - especially the "high quality" breakfasts, with one study showing that a breakfast of low glycemic index foods having an immediate positive effect on attention throughout the morning (1).
In other introductory information, many studies in children have been able to correlate the amount of brain gray matter (vs. white matter) and IQ, especially gray matter in the prefrontal and orbitofrontal cortex and the cingulate gyrus. Therefore, since breakfast types affect cognitive function, and brain structure can correlate with IQ, does breakfast type correlate with brain structure and IQ? I don't know. Let's find out.
These Japanese researchers (funded by a national Young Scientists' grant) studied 290 healthy children ages 5-18 years. In Japan, apparently boiled white rice or white bread make up a typical breakfast. (I remember eating a lot of this cereal plus sugar in skim milk when I was a kid. Kapow!) The scientists were able to split the children into groups of habitual rice-eaters, habitual white bread eaters, and those who consumed both regularly. Then they tested the IQs (using standard measures for kids <16 and a separate standard test for 16 and older), scanned the kids in a MRI, and collected their data. Questionnaires were filled out by the kids or their parents with respect to morning eating habits, health, wealth, etc.
Using varying statistical techniques and a couple varieties of imaging data collection, the researchers found that the gray matter ratios (gray matter volume divided by intracranial volume) were significantly higher among the rice eaters vs. the white bread eaters, even after adjusting for age, gender, wealth, average weekly frequency of eating breakfast, and number of breakfast side dishes. The Verbal IQ in the rice group averaged 104.7, in the bread group 100.3. The Performance IQ was 102.1 in the rice group and 97.9 in the bread group. This difference was non-significant.
As the kids became older, the differences in gray matter ratio increased between bread and rice groups. Overall, calories consumed among rice eaters were slightly lower than those who habitually ate bread.
Now the researchers spend a lot of time talking about how all of these findings can be explained by the lower glycemic index of rice compared to white bread. They feel that low GI foods provide steadier blood glucose levels, and "stable and efficient glucose supply is important for neurons." It is notable that "cerebral metabolic rates of glucose utilization are approximately two times higher in children compared with adults." (Could be why children seem to have so much more of a natural "sweet tooth" than most adults). The researchers also felt that since white bread has more fat than white rice, that the increased fat content might be a problem for the brains of white bread eaters (they suggest fat decreases neuronal plasticity). I rather strongly disagree with them here and will have to pull their supporting paper when I have a minute… right now I have to finish up and dash off to work.
So all told, this study is only an observation, and causal factors cannot be determined with this dataset. And I think the whole high GI/low GI chase is probably a red herring. These Japanese kids were all likely relatively low-fat and high carb compared to say, American kids of the same age, and I do tend to think that healthy, low-toxicity carbs and fruit are fine for kids, who are not as likely to have leptin resistance as their adult counterparts. As for the fat issue - I think a common sense way to think about this issue is to look at neonates. They are the extreme version of the child, after all, and everyone can agree about the best food for them (human breast milk). Neonates need a diet high in sugar (though lactose does not contain fructose) and 50% fat with lots of saturated fat. I don't see how fat can be vital for the baby brain but somehow becomes toxic for the growing child brain. I wish someone could explain that to me in a way that makes any physiologic sense, because it seems to be taken for truth by so many medical professionals and scientists. If you can explain exactly when and how fat becomes toxic (somewhere presumably between the ages of 3 and 5, which is when ancestral humans were weaned?) drop me a comment. "Lipotoxicity" doesn't count without more information as to the specific mechanism - neither do studies poisoning animals and/or humans with large amounts of corn oil or trans fats.
I'm perfectly willing to accept that the bread, derived from wheat, has toxic factors that cause inflammation or hurts the microbiota or interfere with absorption of minerals or whatever, and theoretically could be a casual factor as part of the differences seen in the children's brains in this paper. My kids get rice and potatoes and fruit and milk as carb staples, in addition to meat, fish, nuts, and vegetables. All in all, I believe metabolic flexibility and low-toxicity and premium quality food for premium micronutrients are the most important things for a healthy diet and a healthy brain.
End note - thanks to Jamie for the paper!!! Also, Blogger comments were acting up for a few days. If you asked me a question in the last few posts, I've been meaning to chime in when I get a moment. Don't despair.
As we all know, our big old brains develop not only prenatally, but also throughout childhood and adolescence. In children, several studies have been done showing nourishing breakfasts help cognitive performance compared to skipping breakfast - especially the "high quality" breakfasts, with one study showing that a breakfast of low glycemic index foods having an immediate positive effect on attention throughout the morning (1).
In other introductory information, many studies in children have been able to correlate the amount of brain gray matter (vs. white matter) and IQ, especially gray matter in the prefrontal and orbitofrontal cortex and the cingulate gyrus. Therefore, since breakfast types affect cognitive function, and brain structure can correlate with IQ, does breakfast type correlate with brain structure and IQ? I don't know. Let's find out.
These Japanese researchers (funded by a national Young Scientists' grant) studied 290 healthy children ages 5-18 years. In Japan, apparently boiled white rice or white bread make up a typical breakfast. (I remember eating a lot of this cereal plus sugar in skim milk when I was a kid. Kapow!) The scientists were able to split the children into groups of habitual rice-eaters, habitual white bread eaters, and those who consumed both regularly. Then they tested the IQs (using standard measures for kids <16 and a separate standard test for 16 and older), scanned the kids in a MRI, and collected their data. Questionnaires were filled out by the kids or their parents with respect to morning eating habits, health, wealth, etc.
Using varying statistical techniques and a couple varieties of imaging data collection, the researchers found that the gray matter ratios (gray matter volume divided by intracranial volume) were significantly higher among the rice eaters vs. the white bread eaters, even after adjusting for age, gender, wealth, average weekly frequency of eating breakfast, and number of breakfast side dishes. The Verbal IQ in the rice group averaged 104.7, in the bread group 100.3. The Performance IQ was 102.1 in the rice group and 97.9 in the bread group. This difference was non-significant.
As the kids became older, the differences in gray matter ratio increased between bread and rice groups. Overall, calories consumed among rice eaters were slightly lower than those who habitually ate bread.
Now the researchers spend a lot of time talking about how all of these findings can be explained by the lower glycemic index of rice compared to white bread. They feel that low GI foods provide steadier blood glucose levels, and "stable and efficient glucose supply is important for neurons." It is notable that "cerebral metabolic rates of glucose utilization are approximately two times higher in children compared with adults." (Could be why children seem to have so much more of a natural "sweet tooth" than most adults). The researchers also felt that since white bread has more fat than white rice, that the increased fat content might be a problem for the brains of white bread eaters (they suggest fat decreases neuronal plasticity). I rather strongly disagree with them here and will have to pull their supporting paper when I have a minute… right now I have to finish up and dash off to work.
So all told, this study is only an observation, and causal factors cannot be determined with this dataset. And I think the whole high GI/low GI chase is probably a red herring. These Japanese kids were all likely relatively low-fat and high carb compared to say, American kids of the same age, and I do tend to think that healthy, low-toxicity carbs and fruit are fine for kids, who are not as likely to have leptin resistance as their adult counterparts. As for the fat issue - I think a common sense way to think about this issue is to look at neonates. They are the extreme version of the child, after all, and everyone can agree about the best food for them (human breast milk). Neonates need a diet high in sugar (though lactose does not contain fructose) and 50% fat with lots of saturated fat. I don't see how fat can be vital for the baby brain but somehow becomes toxic for the growing child brain. I wish someone could explain that to me in a way that makes any physiologic sense, because it seems to be taken for truth by so many medical professionals and scientists. If you can explain exactly when and how fat becomes toxic (somewhere presumably between the ages of 3 and 5, which is when ancestral humans were weaned?) drop me a comment. "Lipotoxicity" doesn't count without more information as to the specific mechanism - neither do studies poisoning animals and/or humans with large amounts of corn oil or trans fats.
I'm perfectly willing to accept that the bread, derived from wheat, has toxic factors that cause inflammation or hurts the microbiota or interfere with absorption of minerals or whatever, and theoretically could be a casual factor as part of the differences seen in the children's brains in this paper. My kids get rice and potatoes and fruit and milk as carb staples, in addition to meat, fish, nuts, and vegetables. All in all, I believe metabolic flexibility and low-toxicity and premium quality food for premium micronutrients are the most important things for a healthy diet and a healthy brain.
End note - thanks to Jamie for the paper!!! Also, Blogger comments were acting up for a few days. If you asked me a question in the last few posts, I've been meaning to chime in when I get a moment. Don't despair.
Saturday, July 9, 2011
More Fun With the Gut Microbiota and the Brain (In Mice)
Everyone has been tweeting this new paper, and I have to say, it's a doozy. I don't recommend that many papers, as most are fairly painful to read (though many papers are full of interesting facts, they don't teach scientists how to write), but if you can get your hands on this one, please do so.
The Intestinal Microbiota Affect Central Levels of Brain-Derived Neurotropic Factor and Behavior in Mice
Let's dive in. Ooh, I like the first part:
Back to beasties. They have found that colonization of germ-free mice with Bacteroides species affect the expression of messenger RNA that encode for immune and smooth muscle function, gut permeability, and the gut nervous system. Regulation of body weight and pain perception in the skin have also been shown to be affected by changes in microbiota.
In healthy folks, the intestinal microbiota are diverse, and the species relatively stable. In conditions such as inflammatory bowel disease (Crohn's and ulcerative colitis => IBD) and in irritable bowel syndrome (IBS), the beastie species are less diverse and tend to be unstable over time. In both IBD and IBS, depression and anxiety are common, and associated with worse gastrointestinal disease. In IBS, studies have shown 50-90% of the people affected also have psychiatric symptoms. But are the psychiatric symptoms caused by the discomfort and stress of living with irritable or inflammatory bowel conditions, or are the symptoms caused by the same pathology that causes the gut issues - which includes alteration in the intestinal microbiota.
Previous experimental evidence that gut bacteria affect the brain includes:
For this experiment, the researchers obtained some regular and germ-free mice who lived thereafter in level II biocontainment. Some of the germ-free mice remained germ-free. Others got fecal transplants from other mice that had known bacterial species on board. Some of the mice got a whopping dose of antibiotics (that were "nonabsorbable" so presumably only affected the gut microbiota - a separate experiment by which a small amount of antibiotics were injected systemically in some mice acted as a back-up control and did not affect the gut microbiota). Control mice lapped up sterile water instead.
The mice's gut contents were extracted, cultured, and the bacterial DNA and RNA were characterized via polymerase chain reaction and gel electrophoresis, so you could see what kind of beasties survived the various treatments in each experimental and control group of mice. The mice also underwent behavioral testing - how open they were to exploration, how quick they were to step off a raised platform, etc.
In addition (these researchers were pretty darn thorough) - the gut linings were examined for signs of inflammation, and cytokines and neurotransmitter levels in the small intestine and colon were measured. The brains (specifically sections of the hippocampus and amygdala) were extracted and measured for levels of brain-derived neurotrophic factor (BDNF). BDNF is a brain fertilizer whose levels in the hippocampus and amygdala correlate with depression and anxiety symptoms. Low BDNF in the hippocampus is generally bad news and are associated with depression and anxiety symptoms. Antidepressants are thought to work by increasing levels of BDNF there. In the amygdala, the fear center of the brain, lower levels of BDNF seem to correlate with less fear.
Still with me? How about a song. The Strokes - Taken For A Fool (right click to open in new tab or window if you don't want to be shipped away from this page.)
Results. Well, whopping antibiotic administration did affect the beastie species in the guts of the mice. Lactobacilli and Actinobacteria populations increased with the treatment, while the Bacteroides and gamma-proteobacteria decreased (including Shigella and Klebsiella). The mice who had been exposed to antibiotics were more exploratory and less apprehensive than the control mice. After two weeks, however, the behavioral testing of the control and antibiotic-treated mice when back to being the same, and measures of their beastie populations showed they went back to normal. In the germ-free mice, antibiotic administration did nothing to affect their behavior, showing once again it was likely the alterations in the beastie population that caused the behavioral change in the experimental group. And, finally, germ-free mice who got the fecal transplants showed changes in behavior after being colonized compared to the germ-free controls.
So you see, these researchers went backwards, forwards, and sideways to prove their findings. Pretty cool, really.
More results. Mice who got the whopping dose of antibiotics had higher levels of BDNF in the hippocampus and lower amounts of BDNF in the amygdala compared to control mice. These BDNF levels are what you would expect if you have less anxious and fearful mice who are more open to exploring than controls. The antibiotic-treated mice did not have any changes of cytokines in their guts to suggest increased inflammation, or any increased pathologic inflammatory markers under microscope, and there were no changes in gut neurotransmitters. SO - the behavior and BDNF changes had nothing to do with gut inflammation or the enteric nervous system (at least involving the neurotransmitters they tested, which included all the biggies).
Another recent paper showed that mice fed a beef-enriched diet for three months in early childhood (mouse puppyhood?) had improved memory compared to rats fed standard rat chow. (I'm not sure exactly if that can be linked entirely to the gut bacteria, but it is mentioned in this paper and I thought it was a cool fact.)
These researchers have already shown that administration of probiotics could normalize behavior in mice who showed alterations in behavior and mild to moderate gut inflammation.
All told, I think these scientists are beginning to elucidate a pretty fascinating area of interest to psychiatrists, gastroenterologists, and mouse enthusiasts everywhere.
The Intestinal Microbiota Affect Central Levels of Brain-Derived Neurotropic Factor and Behavior in Mice
Let's dive in. Ooh, I like the first part:
The intestinal microbiota is a vast ecosystem that shapes a wide variety of host functions, both within and outside the gastrointestinal tract.Y'all may recall my previous article in which we have evidence that your commensal beasties, which make up 90% of your cells, also control a mouse's brain (and possibly yours.) And something like this paper and this experimental design excite me more than the endocannabinoid/rat paper I wrote about yesterday. I don't doubt that we probably have endocannabinoid receptors for corn oil (which may be activated by all kinds of fats) in our guts, or ones for sweets in our mouths, I'm just not sure what it means when isolated in that way via the sham-feeding and with creepy rat chow liquid diets that immediately drain out and dribble onto the rat cage in a gross gut slurry. However, we do have to keep in mind that these are rodents who diverged from the family tree many many many millions of years ago…
Back to beasties. They have found that colonization of germ-free mice with Bacteroides species affect the expression of messenger RNA that encode for immune and smooth muscle function, gut permeability, and the gut nervous system. Regulation of body weight and pain perception in the skin have also been shown to be affected by changes in microbiota.
In healthy folks, the intestinal microbiota are diverse, and the species relatively stable. In conditions such as inflammatory bowel disease (Crohn's and ulcerative colitis => IBD) and in irritable bowel syndrome (IBS), the beastie species are less diverse and tend to be unstable over time. In both IBD and IBS, depression and anxiety are common, and associated with worse gastrointestinal disease. In IBS, studies have shown 50-90% of the people affected also have psychiatric symptoms. But are the psychiatric symptoms caused by the discomfort and stress of living with irritable or inflammatory bowel conditions, or are the symptoms caused by the same pathology that causes the gut issues - which includes alteration in the intestinal microbiota.
Previous experimental evidence that gut bacteria affect the brain includes:
- In mice, microbiota have been shown to affect the hypothalamic-pituitary response to stress.
- Oral antibiotics seem to help people suffering from neurological complications of end-stage liver disease.
- Pathogenic bacteria introduced into the gut causes anxiety-like behavior in mice.
For this experiment, the researchers obtained some regular and germ-free mice who lived thereafter in level II biocontainment. Some of the germ-free mice remained germ-free. Others got fecal transplants from other mice that had known bacterial species on board. Some of the mice got a whopping dose of antibiotics (that were "nonabsorbable" so presumably only affected the gut microbiota - a separate experiment by which a small amount of antibiotics were injected systemically in some mice acted as a back-up control and did not affect the gut microbiota). Control mice lapped up sterile water instead.
The mice's gut contents were extracted, cultured, and the bacterial DNA and RNA were characterized via polymerase chain reaction and gel electrophoresis, so you could see what kind of beasties survived the various treatments in each experimental and control group of mice. The mice also underwent behavioral testing - how open they were to exploration, how quick they were to step off a raised platform, etc.
In addition (these researchers were pretty darn thorough) - the gut linings were examined for signs of inflammation, and cytokines and neurotransmitter levels in the small intestine and colon were measured. The brains (specifically sections of the hippocampus and amygdala) were extracted and measured for levels of brain-derived neurotrophic factor (BDNF). BDNF is a brain fertilizer whose levels in the hippocampus and amygdala correlate with depression and anxiety symptoms. Low BDNF in the hippocampus is generally bad news and are associated with depression and anxiety symptoms. Antidepressants are thought to work by increasing levels of BDNF there. In the amygdala, the fear center of the brain, lower levels of BDNF seem to correlate with less fear.
Still with me? How about a song. The Strokes - Taken For A Fool (right click to open in new tab or window if you don't want to be shipped away from this page.)
Results. Well, whopping antibiotic administration did affect the beastie species in the guts of the mice. Lactobacilli and Actinobacteria populations increased with the treatment, while the Bacteroides and gamma-proteobacteria decreased (including Shigella and Klebsiella). The mice who had been exposed to antibiotics were more exploratory and less apprehensive than the control mice. After two weeks, however, the behavioral testing of the control and antibiotic-treated mice when back to being the same, and measures of their beastie populations showed they went back to normal. In the germ-free mice, antibiotic administration did nothing to affect their behavior, showing once again it was likely the alterations in the beastie population that caused the behavioral change in the experimental group. And, finally, germ-free mice who got the fecal transplants showed changes in behavior after being colonized compared to the germ-free controls.
So you see, these researchers went backwards, forwards, and sideways to prove their findings. Pretty cool, really.
More results. Mice who got the whopping dose of antibiotics had higher levels of BDNF in the hippocampus and lower amounts of BDNF in the amygdala compared to control mice. These BDNF levels are what you would expect if you have less anxious and fearful mice who are more open to exploring than controls. The antibiotic-treated mice did not have any changes of cytokines in their guts to suggest increased inflammation, or any increased pathologic inflammatory markers under microscope, and there were no changes in gut neurotransmitters. SO - the behavior and BDNF changes had nothing to do with gut inflammation or the enteric nervous system (at least involving the neurotransmitters they tested, which included all the biggies).
The results of this study provide strong evidence for a microbiota-gut-brain-axis that influences brain biochemistry and modulates behavior in adult mice.In another paper, researchers showed that mice lacking a gut sympathetic nervous system (via severing the vagus nerve or using chemical neurotoxins that kill the sympathetic nervous system) were not affected by the addition of Campylobacter (a gut pathogen) to the gut, which induced anxiety in normal mice. Thus the anxiety behavior seemed to be mediated via communication between the gut and brain via the vagus nerve. In the current paper, a group of mice who had a severed vagus nerve and another group who had been exposed to the neurotoxin had the same results as the mice with untouched nervous systems, thus the change in behavior and changes in BDNF in the brain brought on by antibiotic treatment in the gut occurred through another mechanism - the researchers thought substances produced by the gut bacteria likely acted directly or indirectly on the central nervous system somehow.
Another recent paper showed that mice fed a beef-enriched diet for three months in early childhood (mouse puppyhood?) had improved memory compared to rats fed standard rat chow. (I'm not sure exactly if that can be linked entirely to the gut bacteria, but it is mentioned in this paper and I thought it was a cool fact.)
These researchers have already shown that administration of probiotics could normalize behavior in mice who showed alterations in behavior and mild to moderate gut inflammation.
All told, I think these scientists are beginning to elucidate a pretty fascinating area of interest to psychiatrists, gastroenterologists, and mouse enthusiasts everywhere.
Friday, July 8, 2011
Endocannabinoids, Fat, and Rats
There has been a flurry of rather interesting my-style Evolutionary Psychiatry papers out this week. Tomorrow (I hope), I'll review some findings about probiotics, gut microbiota, and brain function (in rodents, alas), and there is also a paper Jamie sent me about how breakfast staple types are correlated with gray matter and cognitive function in healthy children (If you have but two breakfast choices and you are forced to rely on correlative data, should you feed your children bread or rice if you are playing it safe and interested in protecting their growing brains? Guess.) Jamie might blog that one first, actually. Who knows. Today, though, I'm looking at the paper Endocannabinoid signal in the gut controls dietary fat intake published in PNAS.
First off, I've added two new blogs to my "Of Like Minds" listing on the right, Chris Kresser's Healthy Skeptic, and Anastasia's Primalmeded. I've been meaning to add Chris for some time, but never really got around to it. He's terrific and thoughtful. Anastasia is a mom and medical student in Australia. I find her relatively new blog to be no-nonsense and refreshing.
Now, the endocannabinoid paper. Well. If you haven't seen them yet, I've covered endocannabinoids previously:
For some background in rat studies, I am far more familiar with the binge eating literature than the obesity literature. All the bingeing literature I'm aware of has been done with omega 6 fats (usually Crisco, though trans-fat free Crisco was used for more recent studies) and grains and sugar, and the consistent findings are: Rats will binge on sugar or fat (omega 6). Only the combination of sugar and fat resulted in weight gain (otherwise bingeing rats will make up for extra calories by spontaneously restricting at other times). One study showed bingeing rats maintained their weight but increased fat mass bingeing on crisco (I think. I have to recheck that one. I'll check and edit later if I am misremembering.)
The major distinction in this literature comparing rats to humans is that humans do not typically binge on fat alone, but are far more likely to binge on pasta, bread, sweet foods, chocolate, and salty snacks. The bingeing literature may not have the same focus and may not be as important to the overall state of obesity as the straight-up obesity literature - but with respect to "munchies" and endocannabinoids, I think it is a fair backdrop.
Alrighty then. In the new paper, researchers gave rats "sham" feedings of (okay, three guesses as to what they used as the fat? Pasture butter? Coconut oil? Lard? WRONG) corn oil, a mixed "nutritionally complete" diet, sugar solutions, and protein solutions. How do you sham feed a rat? Well, very unpleasantly. You install an aluminum cannula into the stomach and let the liquid food drain out as you allow the rats to eat a liquid diet of the aforementioned macronutrients. Mmmm. A spoonful of corn oil. Delicious.
Here is what the researchers think about eating fat:
Mammals have an adaptive advantage in seeking fat-rich foods, which are nutritionally essential but scarce in most natural habitats. This innate preference can become maladaptive… when it is not limited by environmental constraints. Indeed, the unrestricted availability of fatty foods, which characterizes diets of industrial societies, is considered to be a key contributing factor for obesity, diabetes, and cardiovascular disease.
Now a little review of endocannabinoids. They are a happy little family of omega-6 derived bioactive molecules that bind to the cannabis receptors (CB1 and CB2). These receptors are also activated by cannabis. The two best studied endocannabinoids are 2-AG and anandamide.
The researchers in this study were trying to further elucidate the mechanisms by which endocannabinoid feedback goes between the mouth, gut, and brain. It has been found previously that CB1 receptors on the tongue modulate neural activity elicited by a sweet taste (1). Neural signals from nutrients - including fats and sugars, are transmitted from the mouth to the brain via the cranial nerves (specifically V, VII, IX, and X). The twelve pairs of cranial nerves shoot out directly from the brain rather than being shuffled through the spinal cord first. Most of them predictably control stuff in the head and neck. One of the cranial nerves, the vagus (X), takes a long trip down to the gut, and seems to be responsible for a lot of the brain regulation of the gut and digestive system, and carries the feedback between the two areas.
So, what happened with the sham feeding of sugar solution, protein solution, corn oil, or a mixed liquid diet and brain and nerve activity in these rats? Levels of the endocannabinoids 2-AG and anadamide were increased in the jejunum (the middle part of the small intestine) of rats fed the corn oil or mixed liquid diet, but not in rats fed the protein or sugar solutions. None of the solutions changed the jejunal content of oleoethanolamide, a fat-derived molecule that typically signals satiety and is usually released by the small intestine in response to the ingestion of fat.
Interestingly, severing the vagus nerve in these rats stopped the production of the endocannabinoids when the rats were sham-fed the corn oil. This would suggest that feedback from the brain is required to produce endocannabinoids in the small intestine in response to a corn oil signal from the small intestine.
The researchers did some more complicated work studying different entities along the metabolic pathways of the endocannabinoids to figure out exactly how the endocannabinoid levels increased. Sham-feeding of corn oil didn't affect the generation of 2-AG, but did seem to slow down the natural breakdown of 2-AG (which is typically done via hydrolysis, biochem nerds.) As for anandamide, the other popular endocannabinoid, sham-fat feeding both increased its production and decreased its breakdown.
In another twist of the study, the researchers measured the amount of corn oil or regular chow the rats consumed while they infused rimonabant, a cannabis receptor inverse agonist (in simplistic terms, it blocks the ability of the endocannabinoids to activate the cannabis receptors) into the jejunum. The rats ate much less corn oil when they had guts full of rimonabant, and to a lesser extent, less regular chow. Thus the researchers conclude that eating fat increases a positive feedback mechanism causing increased ingestion of foods (especially more fat) via a endocannabinoid signal between the gut and the brain along the vagus nerve. They were excited to try gut-specific cannabis receptor blockers that wouldn't have all the pesky anxiety, insomnia, and depression side effects that rimonabant (which is active in the brain) does as a treatment for obesity. It is also known (in rats) that small-intestine levels of 2-AG and anandamide rise in repsonse to food deprivation and fall upon refeeding, suggesting they may signal energy balance and promote caloric intake.
And, last but not least, the discussion goes into details about how reward area dopamine stimulation is affected by feeding rats fat-rich foods. I don't have time to chase down all those papers right now, but let's guess which fat was used in those studies as well…
My take? Sure, play it safe. Don't eat spoonfuls of corn oil. Especially if you are a rat. But elucidating some of these pathways is definitely interesting. If there is some reason we should be extrapolating the sham feeding results to whole, real food eating in humans, please explain. It seems to me the finding that the normal small intestinal fat satiety feedback molecule, oleoethanolamide, was not elevated with sham-feeding of corn oil or the mixed diets or sugar or protein suggests this model is incomplete at best.
Tuesday, July 5, 2011
Healthy Skeptic Podcast
I was very honored to be asked to be interviewed on the Healthy Skeptic Podcast by the amazing Chris Kresser - here's the link:
Healthy Skeptic Podcast, Episode 13
There's also a new paper claiming that eating fat increases appetite by modulating the endocannabinoid system - when I checked earlier the paper wasn't up on pubmed yet but I will track it down and see if it passes the sniff test.
In the meantime, enjoy the podcast!
Healthy Skeptic Podcast, Episode 13
There's also a new paper claiming that eating fat increases appetite by modulating the endocannabinoid system - when I checked earlier the paper wasn't up on pubmed yet but I will track it down and see if it passes the sniff test.
In the meantime, enjoy the podcast!
Sunday, July 3, 2011
Diet-Induced Obesity and Brain Changes
At the beginning of this year, an interesting French study was published, Changes in Brain Activity After a Diet-Induced Obesity. Don't get too excited - they used pigs, not humans, specifically "mini-pigs," which sound awesome. In short, they put two sets of pigs on either standard pig crap lab diet with controlled calories to keep them lean, or a crap lab diet with extra carb and extra fat ad libitum for 5 months. They did SPECT scans of the pigs' brains before and after, and also (in a separate paper) were able to determined that the now-obese pigs had insulin resistance.
First, though, let's start with some human data and take a tour of some parts of the brain. Let's introduce ourselves to the prefrontal cortex. Okay, so when Tom Naughton does his head bangs on his desk, I'm guessing he's whacking his prefrontal cortex (which we are going to call the PFC). It's the area that hangs out over your eyes. Fortunately this habit has not seemed to harm his brain function, if his recent terrific articles are any measure.
Now the prefrontal cortex is more developed and extensive in humans than any other primate, and it is responsible for what is called "executive function." That is, the PFC helps us predict outcomes, prioritize, modulate our emotions to socially acceptable norms, and helps us sort out the best options given conflicting data (reasoning, basically). It is a bit like a policeman for your brain - sure, it would be super fun to get drunk as a skunk and throw beer bottles off your roof at the neighbors - but your policeman says, er, no, that might get you in trouble. Drinking alcohol, in fact, disinhibits the PFC which enables you to ask out the girl you wouldn't have approached sober. Of course, if you are making a selection with impaired reasoning, the girl you ask out might not look quite so good to you sober…
But back to obesity. Our brains do play a major role in whether we gain fat or not. And part of what happens in obese humans is that the prefrontal cortex seems to be less active than in lean humans. This finding is especially interesting in obesity, as the PFC sends nerve fibers to the core appetite regulation part of the brain (the "central orexigenic network") - presumably, when fully active, the policeman is shaking his night stick at you when you want to go to the fridge for that second helping of ice cream. Nuh uh. You have had enough. If the policeman is offline, it may be easier to consume extra helpings. (I'm not sure I like the policeman analogy so much - too close to lack of willpower or gluttony and sloth, but it does fit into the model of weird modern food poisoning our brains, so that the reasoning piece of our appetite regulation machinery is shot.)
Now the question is, obviously - do obese humans start out with underactive PFCs, or is it acquired along with obesity? Well, women who were obese with underactive PFCs regained their frontal lobe function with successful weight loss.* This evidence would suggest that underactive PFCs aren't hard-wired, but depend upon the environment, including nutrition. However, a study going the opposite direction - starting with lean humans and making some obese with controlled overfeeding for an extended period is a tough sell to the institutional review board these days. So it is easier to use mini-pigs, who also seem to have particularly well-developed PFCs.
Let's look at the experiment. 17 pigs, 9 kept lean and 8 made obese. One of the SPECT scans in one of the obese pigs was "unusable" so the data is for 9 lean and 7 obese.
Now the obese diet:
The results of the experiment - well, one interesting thing is that the dietary pattern of the fattening pigs changed. The control pigs ate all their food at once, each morning, but as the "Western Diet" pigs became more obese they would eat 4-5 meals a day, and then spontaneously fast for a day or several days. By the end of the 5 months, the lean pigs weighed 38 kg on average (which is about where they started). The obese pigs weighed 67.1 kg. That's pretty impressive for five months. The day before the final brain imaging, the lean pigs ate 1561 calories each, and the obese pigs ate 2183 calories each.
And, as expected, the brains of the obese pigs did indeed have decreased activity in the PFC, both in the dorsolateral prefrontal areas and the anterior prefrontal cortex. In addition, there was a lessening of activity in some brain areas associated with the "reward system" (specifically the nucleus accumbens, the ventral tegmentum, and the nucleus pontis), which is consistent with the addiction literature - people who are addicted to something have less activation of the reward areas of the brain in response to the addictive stimulus than people who are not addicted. Thus addicted people need more and more of the stimulus to feel reward.
A key finding is that the decreased activation of the PFC correlated significantly with the final weight of the pigs - so the more obese they became, the more depressed their PFC function tended to be.
So, we have learned that in mini-pigs, sunflower oil, wheat bran, cornstarch, and sacchralose is a quick recipe for obesity, and that pigs on a similar diet minus so much cornstarch and oil will stay the same weight as long as you feed them controlled calories… (which is something of a weakness of the study if they were trying to prove that sunflower oil and starch make you fat, which they weren't, but it would have been interesting to see what happened if both groups were fed ad libitum. )
So, in all likelihood, given the corresponding human data in the reverse trial and observationally, the PFC does indeed play an important role in feeding signals and hunger/satiety states. And I'll quote the researchers here: "Whether the alteration of the brain dopamine system and prefrontal cortex metabolism is a cause or a consequence of obesity is still unknown. The answer brought by our study is that less activation of the prefrontal cortex is definitely an acquired anomaly related to obesity, and not a "hard-wired" feature."
*I framed that sentence the way the mini-pig paper did, using "regained frontal lobe function" - however, in the original paper the womens' frontal lobe function was not measured prior to the weight loss, so it is also possible that the women who successfully lost weight were a subset who had better frontal lobe function - but in that study the obese women had decreased PFC metabolism, the lean and formerly-obese women had PFC metabolism indistinguishable from each other.
Also - for more dopamine/frontal lobe/obesity discussion - a post from last year, ADHD and Obesity.
First, though, let's start with some human data and take a tour of some parts of the brain. Let's introduce ourselves to the prefrontal cortex. Okay, so when Tom Naughton does his head bangs on his desk, I'm guessing he's whacking his prefrontal cortex (which we are going to call the PFC). It's the area that hangs out over your eyes. Fortunately this habit has not seemed to harm his brain function, if his recent terrific articles are any measure.
Now the prefrontal cortex is more developed and extensive in humans than any other primate, and it is responsible for what is called "executive function." That is, the PFC helps us predict outcomes, prioritize, modulate our emotions to socially acceptable norms, and helps us sort out the best options given conflicting data (reasoning, basically). It is a bit like a policeman for your brain - sure, it would be super fun to get drunk as a skunk and throw beer bottles off your roof at the neighbors - but your policeman says, er, no, that might get you in trouble. Drinking alcohol, in fact, disinhibits the PFC which enables you to ask out the girl you wouldn't have approached sober. Of course, if you are making a selection with impaired reasoning, the girl you ask out might not look quite so good to you sober…
But back to obesity. Our brains do play a major role in whether we gain fat or not. And part of what happens in obese humans is that the prefrontal cortex seems to be less active than in lean humans. This finding is especially interesting in obesity, as the PFC sends nerve fibers to the core appetite regulation part of the brain (the "central orexigenic network") - presumably, when fully active, the policeman is shaking his night stick at you when you want to go to the fridge for that second helping of ice cream. Nuh uh. You have had enough. If the policeman is offline, it may be easier to consume extra helpings. (I'm not sure I like the policeman analogy so much - too close to lack of willpower or gluttony and sloth, but it does fit into the model of weird modern food poisoning our brains, so that the reasoning piece of our appetite regulation machinery is shot.)
Now the question is, obviously - do obese humans start out with underactive PFCs, or is it acquired along with obesity? Well, women who were obese with underactive PFCs regained their frontal lobe function with successful weight loss.* This evidence would suggest that underactive PFCs aren't hard-wired, but depend upon the environment, including nutrition. However, a study going the opposite direction - starting with lean humans and making some obese with controlled overfeeding for an extended period is a tough sell to the institutional review board these days. So it is easier to use mini-pigs, who also seem to have particularly well-developed PFCs.
Let's look at the experiment. 17 pigs, 9 kept lean and 8 made obese. One of the SPECT scans in one of the obese pigs was "unusable" so the data is for 9 lean and 7 obese.
The standard diet was composed of 33% barley, 25% wheat bran, 12% soy shell, 10% wheat, 10% sunflower meal, 6% soy meal, and other minor components. Fat provided 2.17% of the total nutritional value.Well, if in much of pig evolutionary history they were set loose in a warehouse of a cardiologist's favorite Power Bar ingredients, perhaps this is what the minipigs would eat these days and stay nice and lean and metabolic syndrome free. In this experiment the pigs were fed 102 calories per kilogram each morning, and the pigs dutifully ate their swill in one meal and did their piggy things and stayed lean. Since calories are calories…though I will get back to the standard diet later...
Now the obese diet:
…eight animals were fed with a Western Diet (WD) enriched with carbohydrates and lipids offered ad libitum during 5 months (one ration offered at 0900 hours and calculated to exceed daily calorie consumption of the animals. The WD was composed of 32.65% wheat, 15% soy meal, 12% wheat bran, 10% barley, 10% sunflower oil, 10% cornstarch, 5% saccharose, and other minor components. Fat provided 22.74% of the total nutritional value.Gak! Enough said. I wonder if this was that high-oleic sunflower oil. Anyway….
The results of the experiment - well, one interesting thing is that the dietary pattern of the fattening pigs changed. The control pigs ate all their food at once, each morning, but as the "Western Diet" pigs became more obese they would eat 4-5 meals a day, and then spontaneously fast for a day or several days. By the end of the 5 months, the lean pigs weighed 38 kg on average (which is about where they started). The obese pigs weighed 67.1 kg. That's pretty impressive for five months. The day before the final brain imaging, the lean pigs ate 1561 calories each, and the obese pigs ate 2183 calories each.
And, as expected, the brains of the obese pigs did indeed have decreased activity in the PFC, both in the dorsolateral prefrontal areas and the anterior prefrontal cortex. In addition, there was a lessening of activity in some brain areas associated with the "reward system" (specifically the nucleus accumbens, the ventral tegmentum, and the nucleus pontis), which is consistent with the addiction literature - people who are addicted to something have less activation of the reward areas of the brain in response to the addictive stimulus than people who are not addicted. Thus addicted people need more and more of the stimulus to feel reward.
A key finding is that the decreased activation of the PFC correlated significantly with the final weight of the pigs - so the more obese they became, the more depressed their PFC function tended to be.
So, we have learned that in mini-pigs, sunflower oil, wheat bran, cornstarch, and sacchralose is a quick recipe for obesity, and that pigs on a similar diet minus so much cornstarch and oil will stay the same weight as long as you feed them controlled calories… (which is something of a weakness of the study if they were trying to prove that sunflower oil and starch make you fat, which they weren't, but it would have been interesting to see what happened if both groups were fed ad libitum. )
So, in all likelihood, given the corresponding human data in the reverse trial and observationally, the PFC does indeed play an important role in feeding signals and hunger/satiety states. And I'll quote the researchers here: "Whether the alteration of the brain dopamine system and prefrontal cortex metabolism is a cause or a consequence of obesity is still unknown. The answer brought by our study is that less activation of the prefrontal cortex is definitely an acquired anomaly related to obesity, and not a "hard-wired" feature."
*I framed that sentence the way the mini-pig paper did, using "regained frontal lobe function" - however, in the original paper the womens' frontal lobe function was not measured prior to the weight loss, so it is also possible that the women who successfully lost weight were a subset who had better frontal lobe function - but in that study the obese women had decreased PFC metabolism, the lean and formerly-obese women had PFC metabolism indistinguishable from each other.
Also - for more dopamine/frontal lobe/obesity discussion - a post from last year, ADHD and Obesity.
Saturday, July 2, 2011
Primal Docs and a Whole30
Hello there! Happy July. I've barely had a moment to do anything but tweet and follow the latest posts, but I did find this paper from January that I had meant to blog about - I believe Jamie sent it to me, and he did write about it… but it is interesting enough for a second look to be sure. I'll have a blog up on that one tomorrow.
Before that, though, I'd like to point your compasses to a couple of things. First off, Chris Armstrong of The Celiac Handbook approached me after reading my Wheat and Schizophrenia post over at Psychology Today. Turns out that Chris himself basically follows a primal/paleo lifestyle, and he developed the website Primal Docs in order to create a resource for people to find physicians (typically MDs or DOs) who would support and understand that lifestyle. You'll notice I'm one of the doctors over there, along with John Biffra and a growing group of very healthy-looking folks! I have to say it does disturb me that so many doctors seem to be struggling with metabolic syndrome these days. If doctors can't keep themselves healthy with all that supposed discipline and knowledge, how is it that everyone else can? And sure, doctors are only human, and perhaps it is good for a doctor to be a patient every now and again, but on the other hand, I wouldn't go to a mechanic whose car is always broken down.
Secondly, beginning yesterday I started a stricter little stint of paleo eating called the Whole30. The plan was designed by Dallas and Melissa Hartwig of Whole9Life, and in full disclosure they did send me a complimentary copy of their handbook, though they did not ask me to follow the program or mention them on my blog. The Whole30 is a bit different than my typical routine because there is to be no cheating, no added sugars, no sugarfree gum, no sugar substitutes (which I don't use except for the occasional Diet Coke. I know. I know. I'm addicted. I can stop drinking it for long periods, but I still crave it for some reason, and I would actually drink regular Coke instead, except that it is so sweet I can't stand it… so...) no alcohol, no white rice or white potatoes, and no dairy of any kind.
In my ordinary day-to-day eating I don't consider wine or dark chocolate a "cheat," white potatoes and white rice I consider perfectly fine though a bit less nutrient dense calorie per calorie than other foods, and I will regularly partake of some high-fat dairy (maybe some yogurt or heavy cream once a week, cheese once or twice a week, and pasture butter on a near daily basis). Also, every once in a while I will cook some things with raw honey or real maple syrup and I don't give it a second thought. Once a month I have some honey in my tea, even. Otherwise, I'll eat just about anything (such as a couple of slices of pizza, ice cream, bbq ribs from a restaurant, a miniature snickers bar from my daughters' halloween stash, mexican food complete with refried beans and a *few* corn chips, some restaurant french fries, even a cookie) maybe once every couple of weeks. What Mark Sisson would consider the "20%" I suppose, though it wouldn't equal nearly 20% of my diet if you don't count the white rice and potatoes or dark chocolate - I've had Mexican food probably twice this year so far, BBQ ribs twice, pizza (my most common cheat) once a month - you get the idea.
And in the past, maintaining my normal weight was a constant battle of exercising and accounting for macronutrients and scarfing down low-fat yogurt and cottage cheese… any night out at a restaurant or extra ice cream or whatever would have to be meticulously made up for, or my weight would creep up. Ever since switching to the paleo lifestyle (including IF), as long as I stick to it the majority of the time, I've been able to eat whatever I want (every now and again), decrease the amount of time spent exercising, and my weight doesn't budge. Which is nice. It takes all the worry out of eating, and some of the naughtiness out of cheating. I don't cheat because I'm craving (except the Diet Coke, which is the only cheat I'm ashamed of…), I cheat because Mexican Food can taste good, especially if you don't eat it all the time.
The first three months of paleo I was very strict with my plan, which was also dairy-free, alcohol free, and entirely gluten-free. While doing that plan, I stumbled upon the Primal Blueprint and what then was PaNu and Whole Health Source and did a lot more of my own investigating, which led me to my blog, of course, and eventually reading Perfect Health Diet. Thus developed my day to day eating, which is sort of a cross between PB and PHD, and right now I only supplement with a multimineral in the morning and magnesium at night.
I haven't been super-strict since July of last year, which is also when I stopped losing weight, I think. So in combination with CrossFit I wanted to see if I could get a bit leaner, and the support of the Whole30 twitter crowd seemed like a good way to do it. I feel good for the most part - maybe I will even feel better. Who knows. And while I don't think a tiny bit of casein in pasture butter or a tiny bit of honey in my tea or a glass of wine or white rice and white potatoes are major problems, the idea of the Whole30 is to banish any sugar cravings (which I don't think I have - unless that is part of the Diet Coke monster - though it is not just the aspartame, as I don't crave Diet Pepsi or those weird diet iced teas and Diet Dr. Pepper I gave up years and years ago because gives me a sugar crash, weirdly enough - it's just Diet Coke. Very strange. What do they put in that stuff?), and to have your diet consist entirely of very nutrient-dense foods. While moderate alcohol and white potatoes and white rice are fairly innocuous, they do reduce the nutrient density of the day.
Right now I'm in the middle of Day 2, and have a bunch of veggies and high quality protein at the ready, and will be substituting sweet potatoes and squash and probably a second daily serving of fruit for the white potatoes and rice, and coconut oil and olive oil for my usual butter. I'm not gonna lie - because I don't want to cook two separate meals all the time, and I like to get K2 into the kids, I'll be using pasture ghee from time to time, and I'm going to consider that Whole30 compliant too. This bit is a little deviation from Dallas and Melissa's advice - It's just 30 days, just do what we say and don't tweak. But I'm fairly certain that will be my only deviation. A lovely chilled glass of pinot grigio (and the fizz from the Diet Coke, I suppose) has been replaced with San Pellegrino Sparkling Natural Mineral Water and lime. It's inexpensive, has some minerals, and I always feel very sophisticated drinking it.
I do have a vacation planned in a few weeks - and that will be the hardest week of the Whole30, I'm sure. Well, we will see how it goes!
Before that, though, I'd like to point your compasses to a couple of things. First off, Chris Armstrong of The Celiac Handbook approached me after reading my Wheat and Schizophrenia post over at Psychology Today. Turns out that Chris himself basically follows a primal/paleo lifestyle, and he developed the website Primal Docs in order to create a resource for people to find physicians (typically MDs or DOs) who would support and understand that lifestyle. You'll notice I'm one of the doctors over there, along with John Biffra and a growing group of very healthy-looking folks! I have to say it does disturb me that so many doctors seem to be struggling with metabolic syndrome these days. If doctors can't keep themselves healthy with all that supposed discipline and knowledge, how is it that everyone else can? And sure, doctors are only human, and perhaps it is good for a doctor to be a patient every now and again, but on the other hand, I wouldn't go to a mechanic whose car is always broken down.
Secondly, beginning yesterday I started a stricter little stint of paleo eating called the Whole30. The plan was designed by Dallas and Melissa Hartwig of Whole9Life, and in full disclosure they did send me a complimentary copy of their handbook, though they did not ask me to follow the program or mention them on my blog. The Whole30 is a bit different than my typical routine because there is to be no cheating, no added sugars, no sugarfree gum, no sugar substitutes (which I don't use except for the occasional Diet Coke. I know. I know. I'm addicted. I can stop drinking it for long periods, but I still crave it for some reason, and I would actually drink regular Coke instead, except that it is so sweet I can't stand it… so...) no alcohol, no white rice or white potatoes, and no dairy of any kind.
In my ordinary day-to-day eating I don't consider wine or dark chocolate a "cheat," white potatoes and white rice I consider perfectly fine though a bit less nutrient dense calorie per calorie than other foods, and I will regularly partake of some high-fat dairy (maybe some yogurt or heavy cream once a week, cheese once or twice a week, and pasture butter on a near daily basis). Also, every once in a while I will cook some things with raw honey or real maple syrup and I don't give it a second thought. Once a month I have some honey in my tea, even. Otherwise, I'll eat just about anything (such as a couple of slices of pizza, ice cream, bbq ribs from a restaurant, a miniature snickers bar from my daughters' halloween stash, mexican food complete with refried beans and a *few* corn chips, some restaurant french fries, even a cookie) maybe once every couple of weeks. What Mark Sisson would consider the "20%" I suppose, though it wouldn't equal nearly 20% of my diet if you don't count the white rice and potatoes or dark chocolate - I've had Mexican food probably twice this year so far, BBQ ribs twice, pizza (my most common cheat) once a month - you get the idea.
And in the past, maintaining my normal weight was a constant battle of exercising and accounting for macronutrients and scarfing down low-fat yogurt and cottage cheese… any night out at a restaurant or extra ice cream or whatever would have to be meticulously made up for, or my weight would creep up. Ever since switching to the paleo lifestyle (including IF), as long as I stick to it the majority of the time, I've been able to eat whatever I want (every now and again), decrease the amount of time spent exercising, and my weight doesn't budge. Which is nice. It takes all the worry out of eating, and some of the naughtiness out of cheating. I don't cheat because I'm craving (except the Diet Coke, which is the only cheat I'm ashamed of…), I cheat because Mexican Food can taste good, especially if you don't eat it all the time.
The first three months of paleo I was very strict with my plan, which was also dairy-free, alcohol free, and entirely gluten-free. While doing that plan, I stumbled upon the Primal Blueprint and what then was PaNu and Whole Health Source and did a lot more of my own investigating, which led me to my blog, of course, and eventually reading Perfect Health Diet. Thus developed my day to day eating, which is sort of a cross between PB and PHD, and right now I only supplement with a multimineral in the morning and magnesium at night.
I haven't been super-strict since July of last year, which is also when I stopped losing weight, I think. So in combination with CrossFit I wanted to see if I could get a bit leaner, and the support of the Whole30 twitter crowd seemed like a good way to do it. I feel good for the most part - maybe I will even feel better. Who knows. And while I don't think a tiny bit of casein in pasture butter or a tiny bit of honey in my tea or a glass of wine or white rice and white potatoes are major problems, the idea of the Whole30 is to banish any sugar cravings (which I don't think I have - unless that is part of the Diet Coke monster - though it is not just the aspartame, as I don't crave Diet Pepsi or those weird diet iced teas and Diet Dr. Pepper I gave up years and years ago because gives me a sugar crash, weirdly enough - it's just Diet Coke. Very strange. What do they put in that stuff?), and to have your diet consist entirely of very nutrient-dense foods. While moderate alcohol and white potatoes and white rice are fairly innocuous, they do reduce the nutrient density of the day.
Right now I'm in the middle of Day 2, and have a bunch of veggies and high quality protein at the ready, and will be substituting sweet potatoes and squash and probably a second daily serving of fruit for the white potatoes and rice, and coconut oil and olive oil for my usual butter. I'm not gonna lie - because I don't want to cook two separate meals all the time, and I like to get K2 into the kids, I'll be using pasture ghee from time to time, and I'm going to consider that Whole30 compliant too. This bit is a little deviation from Dallas and Melissa's advice - It's just 30 days, just do what we say and don't tweak. But I'm fairly certain that will be my only deviation. A lovely chilled glass of pinot grigio (and the fizz from the Diet Coke, I suppose) has been replaced with San Pellegrino Sparkling Natural Mineral Water and lime. It's inexpensive, has some minerals, and I always feel very sophisticated drinking it.
I do have a vacation planned in a few weeks - and that will be the hardest week of the Whole30, I'm sure. Well, we will see how it goes!