Senin, 27 Juni 2011
Rabu, 22 Juni 2011
One thing I hardly ever do is discuss what most people would consider real "Evolutionary Psychiatry." That is, how do diseases such as schizophrenia or autism, which in their worst forms are obviously so detrimental to evolutionary fitness that they would seem to represent a genetic dead end, continue in the gene pool. It doesn't make much sense at first glance. However, one could postulate that, just as the heterozygote carriers of sickle cell anemia are relatively protected against malaria, having some schizophrenia-risk genes could convey some sort of benefit for close relatives. And one must also consider the possibility that the schizophrenia phenotype is worse now than it may have been for much of human history - with plenty of vitamin D, no wheat (speculatively :-) ) or common modern pathogens, it is possible the schizophrenia may not have developed as fully or been as debilitating.
Given dopamine's role in creativity, motivation, and drive, the suspected genetic advantage of being a relative of a schizophrenic is that you may have a bit of extra dopamine, but not so much it will make you psychotic. Psychotic thought is disjointed and disorganized - creative thought is taking seemingly unrelated or unexpected ideas and bringing them together in a novel way.
Sounds reasonable. But what about the data proving it? Well, there has been a lot of speculation looking back at known geniuses and their psychopathologies. It is felt it is no coincidence that many geniuses were not particularly psychologically healthy. A more recent study selected 30 creative writers at a workshop and compared them to controls - writers had higher rates of affective disorders (several variations of this study have been done with the same results). Studies of bipolar individuals showed they scored higher on scales measuring creativity than folks with unipolar depression or non-creative controls - the bipolar folks scored the same as creative healthy controls.
In Iceland, the histories of 486 male relatives of schizophrenics were investigated - these men were more likely to be prominent historically than the general population, and there was a significant increase in those who were specifically successful in creative endeavors.
But all those studies are small, and many rely on historical records. However, a brand new paper from the British Journal of Psychiatry documents a large, population based study of 300,000 individuals with severe forms of affective disorders or schizophrenia from a large population registry in Sweden, where there is data on hospital admissions, diagnoses, IQ, occupation, and detailed family records as well. The were able to find several tens of thousands of folks with bipolar disorder and schizophrenia, and over two hundred thousand diagnosed with unipolar depression.
The results? People with schizophrenia and bipolar disorder (with the effect stronger in schizophrenia) were more likely to have parents and siblings who were in creative professions. Bipolar patients also were more likely to have creative offspring. The ORs aren't huge - ranging from around 1.2 to 1.6, but the bars don't cross the 1.0 line suggesting a real correlation. There were no strong statistically significant correlations between having a relative with unipolar depression and engaging in creative professions (described as "including scientific and artistic occupations.") As one would expect for a genetic link, as relationships got further away (half-siblings, cousins, etc.) the correlations weakened accordingly.
The reverse sort of "non-creative" correlation was also true - folks with schizophrenia were significantly less likely to have relatives who were accountants and auditors.
And the IQ connection (only measured in men in this Swedish registry) - those in creative professions had a higher IQ on average, however, the IQs of people with schizophrenia, unipolar depression, bipolar depression and their relatives were lower on average than people without any of the three diagnoses. IQ was accounted for in the correlations we talked about in the previous paragraphs and did not weaken the genetic association between creativity and severe psychiatric illness (specifically bipolar disorder and schizophrenia).
Well. That is all very interesting! I might go on to be a real Evolutionary Psychiatrist after all.
Read More..
Given dopamine's role in creativity, motivation, and drive, the suspected genetic advantage of being a relative of a schizophrenic is that you may have a bit of extra dopamine, but not so much it will make you psychotic. Psychotic thought is disjointed and disorganized - creative thought is taking seemingly unrelated or unexpected ideas and bringing them together in a novel way.
Sounds reasonable. But what about the data proving it? Well, there has been a lot of speculation looking back at known geniuses and their psychopathologies. It is felt it is no coincidence that many geniuses were not particularly psychologically healthy. A more recent study selected 30 creative writers at a workshop and compared them to controls - writers had higher rates of affective disorders (several variations of this study have been done with the same results). Studies of bipolar individuals showed they scored higher on scales measuring creativity than folks with unipolar depression or non-creative controls - the bipolar folks scored the same as creative healthy controls.
In Iceland, the histories of 486 male relatives of schizophrenics were investigated - these men were more likely to be prominent historically than the general population, and there was a significant increase in those who were specifically successful in creative endeavors.
But all those studies are small, and many rely on historical records. However, a brand new paper from the British Journal of Psychiatry documents a large, population based study of 300,000 individuals with severe forms of affective disorders or schizophrenia from a large population registry in Sweden, where there is data on hospital admissions, diagnoses, IQ, occupation, and detailed family records as well. The were able to find several tens of thousands of folks with bipolar disorder and schizophrenia, and over two hundred thousand diagnosed with unipolar depression.
The results? People with schizophrenia and bipolar disorder (with the effect stronger in schizophrenia) were more likely to have parents and siblings who were in creative professions. Bipolar patients also were more likely to have creative offspring. The ORs aren't huge - ranging from around 1.2 to 1.6, but the bars don't cross the 1.0 line suggesting a real correlation. There were no strong statistically significant correlations between having a relative with unipolar depression and engaging in creative professions (described as "including scientific and artistic occupations.") As one would expect for a genetic link, as relationships got further away (half-siblings, cousins, etc.) the correlations weakened accordingly.
The reverse sort of "non-creative" correlation was also true - folks with schizophrenia were significantly less likely to have relatives who were accountants and auditors.
And the IQ connection (only measured in men in this Swedish registry) - those in creative professions had a higher IQ on average, however, the IQs of people with schizophrenia, unipolar depression, bipolar depression and their relatives were lower on average than people without any of the three diagnoses. IQ was accounted for in the correlations we talked about in the previous paragraphs and did not weaken the genetic association between creativity and severe psychiatric illness (specifically bipolar disorder and schizophrenia).
Well. That is all very interesting! I might go on to be a real Evolutionary Psychiatrist after all.
Selasa, 21 Juni 2011
Just to assuage any doubts, I don't ascribe to the humoral theory of disease. (I believe in inflammation - everyone should know that!). However, there is still much to learn from ancient Western medicine. I think there is an idea that Western medicine is all leeches and lipitor, but in fact there is a long and noble history of careful observation, philosophy, and anatomy. And like any psychiatrist, I like to know the background and the nitty gritty - it helps establish the basis for what we think and do today. Western medical thinking has made some missteps - in the past, and recently, and our history helps us understand both our mistakes and our wisdom. I will focus here, as always, on mental health (with the help of Melancholia and Depression: From Hippocratic Times to Modern Times
)
So� Plato and Aristotle and Galen and Hippocrates were not enemies of feeling. Aristotle recognized that strong passions could contribute to motivation, though he felt passions should be directed in ethical and religious directions. A group of philosophers known as the Stoics held sway thereafter - and while Aristotle felt passions ought to be controlled, the Stoics thought they should be done away with. (I am no expert in Eastern philosophy by any means, but this ideal does seem to dovetail with my reading of Siddhartha
and the state of wanting nothing). "One was to avoid whatever might lead to greater tumults of the soul� except in the case of the wise man, they viewed [passions] as perverted judgments. They sought inner peace as the basic good and thought of the passions as disorders of the soul, disturbing to reason and contrary to nature."
The Stoics also believed in the concept of "pneuma," or "spirit." It was a "most subtle material substance� a life-giving principle in the body that was replenished from the air through the lungs and pores of the skin and from the digestion of food." In general, spirit and passions were associated with the heart, and the liver was the seat of baser bodily appetites.
With Stoics and Humors and Passions we bring ourselves forward through the Middle Ages and the Renaissance. In the fourth century we have writers separating the soul into two parts- rational and irrational. The irrational part was divided into basic elements of waste disposal and appetites and desire, and the rational part of thoughts and more noble passions (intellect and religion). Interestingly, at this time, the seat of grief was felt to be the stomach.
The Renaissance writers began to be more flexible about the positives of passions - Aquinas felt that rational passions led to the acquisition of knowledge and fulfilling of the potential via the five senses. Later Renaissance writers devoted more time to passion, spirit, and affects. By the 16th century, the head began to replace the heart as the center of feeling (except perhaps on Valentine's Day).
Descartes made some adjustments of the ancient ideas of the 6 non-naturals - he suggested we focus on the six primary passions instead - surprise (astonishment), love, hate, desire, joy, and sorrow.* He finally felt that passions were felt "by the soul" rather than in the visceral organs.
Later, Hobbes and Spinoza would publish writings describing the baseness of the soul, and how it operated in self-serving interest.
In the end, the "self-serving" meme would come to dominate - and fits in nicely with an evolutionary genetic view. My one observational addition is that doctors of the early 20th century had some "advantages" in training and physical diagnosis that we no longer enjoy. At the time, one might see aortic stenosis and be able to diagnosis the late stage via observation and stethoscope - nowadays an echocardiogram and ultrasound would preempt physical diagnosis.
In addition, the fact that the average American is obese also changes physical diagnoses. In the past, one could readily palpate liver, kidney, aorta, spleen - now an apron of fat is often in the way. We have to rely on ultrasound and CT scan - though the million dollar CT scanners are calibrated to 300 pounds or less - larger patients need to be sent to specialized MRI or CT scanners calibrated to greater weights.
Everything has changed very rapidly with the advent of so many medications and so much adiposity. Medical science has not caught up, having gone the wrong direction with respect to treatment of obesity, and no one knows the consequence of so many medications being recommended all at the same time all at once�we are in a no-man's land of polypharmacy and low-fat living.
Well, I hope we move on from that sooner rather than later. But I'm an optimist.
*My favorite schema for productive psychotherapy was developed by one of my teachers in residency, and a former wife of another teacher of mine, George Valliant, Leigh McCullough - her key book is Treating Affect Phobia: A Manual for Short-Term Dynamic Psychotherapy
) She advises a combination of cognitive work and focus on intolerable emotions, with the Descartes driving passions being primary, whereas the inhibitory emotions of anxiety, boredom, and frustration lead us backwards and only burning up much needed energy.
Read More..
)So� Plato and Aristotle and Galen and Hippocrates were not enemies of feeling. Aristotle recognized that strong passions could contribute to motivation, though he felt passions should be directed in ethical and religious directions. A group of philosophers known as the Stoics held sway thereafter - and while Aristotle felt passions ought to be controlled, the Stoics thought they should be done away with. (I am no expert in Eastern philosophy by any means, but this ideal does seem to dovetail with my reading of Siddhartha
and the state of wanting nothing). "One was to avoid whatever might lead to greater tumults of the soul� except in the case of the wise man, they viewed [passions] as perverted judgments. They sought inner peace as the basic good and thought of the passions as disorders of the soul, disturbing to reason and contrary to nature." The Stoics also believed in the concept of "pneuma," or "spirit." It was a "most subtle material substance� a life-giving principle in the body that was replenished from the air through the lungs and pores of the skin and from the digestion of food." In general, spirit and passions were associated with the heart, and the liver was the seat of baser bodily appetites.
With Stoics and Humors and Passions we bring ourselves forward through the Middle Ages and the Renaissance. In the fourth century we have writers separating the soul into two parts- rational and irrational. The irrational part was divided into basic elements of waste disposal and appetites and desire, and the rational part of thoughts and more noble passions (intellect and religion). Interestingly, at this time, the seat of grief was felt to be the stomach.
The Renaissance writers began to be more flexible about the positives of passions - Aquinas felt that rational passions led to the acquisition of knowledge and fulfilling of the potential via the five senses. Later Renaissance writers devoted more time to passion, spirit, and affects. By the 16th century, the head began to replace the heart as the center of feeling (except perhaps on Valentine's Day).
Descartes made some adjustments of the ancient ideas of the 6 non-naturals - he suggested we focus on the six primary passions instead - surprise (astonishment), love, hate, desire, joy, and sorrow.* He finally felt that passions were felt "by the soul" rather than in the visceral organs.
Later, Hobbes and Spinoza would publish writings describing the baseness of the soul, and how it operated in self-serving interest.
In the end, the "self-serving" meme would come to dominate - and fits in nicely with an evolutionary genetic view. My one observational addition is that doctors of the early 20th century had some "advantages" in training and physical diagnosis that we no longer enjoy. At the time, one might see aortic stenosis and be able to diagnosis the late stage via observation and stethoscope - nowadays an echocardiogram and ultrasound would preempt physical diagnosis.
In addition, the fact that the average American is obese also changes physical diagnoses. In the past, one could readily palpate liver, kidney, aorta, spleen - now an apron of fat is often in the way. We have to rely on ultrasound and CT scan - though the million dollar CT scanners are calibrated to 300 pounds or less - larger patients need to be sent to specialized MRI or CT scanners calibrated to greater weights.
Everything has changed very rapidly with the advent of so many medications and so much adiposity. Medical science has not caught up, having gone the wrong direction with respect to treatment of obesity, and no one knows the consequence of so many medications being recommended all at the same time all at once�we are in a no-man's land of polypharmacy and low-fat living.
Well, I hope we move on from that sooner rather than later. But I'm an optimist.
*My favorite schema for productive psychotherapy was developed by one of my teachers in residency, and a former wife of another teacher of mine, George Valliant, Leigh McCullough - her key book is Treating Affect Phobia: A Manual for Short-Term Dynamic Psychotherapy
) She advises a combination of cognitive work and focus on intolerable emotions, with the Descartes driving passions being primary, whereas the inhibitory emotions of anxiety, boredom, and frustration lead us backwards and only burning up much needed energy. Sabtu, 18 Juni 2011
I know I've left a few threads hanging. I will get back to fat loss and cognition and that diet and dementia paper. In the mean time there are distractions, and I've been diving more deeply into Stanley Jackson's amazing work, Melancholia and Depression: From Hippocratic Times to Modern Times.
I think history is important. Maybe we didn't have microscopes or DNA but we were not sidelined by twitter and TV - and we wrote with lovely handwriting and made terrific observations. Even in the West. Careful observation and history give us the tenets of the paleo diet. From anthropology we learn the concept of the "nutritional transition" from relative health to relative disease.
And in the West, medicine begins with Hippocrates (460-370 BC) and his work, Nature of Man. He was (of course) building on ancient observations and wisdom himself, but from this point we are looking at translated written records, so this is where we must begin.
Humor Season Qualities
Blood Spring warm and moist
Yellow Bile Summer warm and dry
Black Bile Autumn cold and dry
Phlegm Winter cold and moist
In ancient times, the seasons were linked with the four ages of man - Youth, Manhood (Prime), Decline, and Old Age (counted in Ancient times as 0-20, 20-40, 40-60, 60-death - suggesting that ancient agricultural ages corresponded roughly to our own (so much for statins)).
Mental illness in general was derived from the concept of "black bile" - which was interestingly seen to be a perturbation of normal yellow bile from excessive heat or cold (either via environment or via intemperent passions). Black bile in its time was held to be responsible for a great number of diseases, including headaache, vertigo, paralysis, spasms, epilepsy, and other mental disturbances, to diseases of the kidney, liver, and spleen.
Plato felt that the blood was made of two parts, "the watery part" which was innocent, and the part that is "a secretion of black and acid bile" which is potentially malignant. He felt pathologic forms of "the humors" had the potential to wander around the body, and finding "no exit or escape" become "pent up within and mingle their own vapours with the motions of the soul."
By the time of the Middle Ages and Renaissance, variant in the Black Bile theory had come to the fore. There was not only "natural" black bile, but also "burnt black bile" derived from combustion of yellow bile in the absence of fever that provoked "violent delerium� because it occupies the substance of the brain itself." In time, the concept of unnatural black bile evolved so that the process of burning or combustion of the four humors could lead to the bitter black bile, thus it became common to think of four types of black bile derived from the four humors. The causes suggested for such a process were improper diet, physiological disorders, and immoderate passions. The burning process would lead to hot melancholy, which would be followed in turn by cold melancholy.
In ancient Western medicine, the term "non-naturals" referred to a group of environmental factors related to the disease process: 1) air, 2) exercise and rest, 3) sleep and wakefulness, 4) food and drink, 5) excretion and retention of superfluities, and 6) the passions and perturbations of the soul. For hundreds of generations, management of the patient by a physician involved addressing issues with these six factors and bringing the "whole organism" back to equilibrium. (In modern times we call the "non-naturals" model the "Biopsychosocial model" of psychiatric diagnosis.)
By the 18th and 19th centuries, the discovery of microorganisms and other issues leading to pathologic states fed into this model. Just what is disease, anyway?
In any event, "disease" is a deviation from the norm, something added to the healthy state to bring on illness. "Outside" element theories (such as demonic possession) dictated a treatment of removing the offending element. "Inside" element theories involved paying attention to the individual as well as the nature of the disease to best affect a cure. These theories do not differ too significantly from our models of disease and treatment today.
In all cases, disease is relative, varying from culture to culture. Some mental states are considered in all history and culture as distinctly unusual, in other cultures, the mentally ill are considered sinners, with the unusual mental states being reflections of the sins. Others have been thought of as prophets or holy men, and have been honored rather than treated.
I bring up this history because we have to understand that even our modern Western understanding of disease reflects these ancient biases. There are perturbations and demons, strength of moral fiber or lack of temperance. Add in microorganisms, character, maladaptive coping strategies, trauma, genetics, diet� we learn from history the same lessons over and over. It behooves us to listen to our ancestral nutritional and lifestyle programming. The more things change, the more things stay the same.
Read More..
. I think history is important. Maybe we didn't have microscopes or DNA but we were not sidelined by twitter and TV - and we wrote with lovely handwriting and made terrific observations. Even in the West. Careful observation and history give us the tenets of the paleo diet. From anthropology we learn the concept of the "nutritional transition" from relative health to relative disease.
And in the West, medicine begins with Hippocrates (460-370 BC) and his work, Nature of Man. He was (of course) building on ancient observations and wisdom himself, but from this point we are looking at translated written records, so this is where we must begin.
The nature of humors as such comes from empirical medicine. The notion of the tetrad, the definition of health as the equilibrium of the different parts, and of sickness as the disturbance of the equilibrium, are Pythagorean contributions� The notion that in the course of the seasons each of the four substances in turn gains ascendancy seems to be purely Empedoclean. But the credit for combining all these notions in one system, and thereby creating the doctrine of humoralism which was to dominate the future, is not doubt due to the powerful writer who composed the first part of� [Nature of Man]� from this� evolved the following schema, which was to remain in force for more than two thousand years.
Humor Season Qualities
Blood Spring warm and moist
Yellow Bile Summer warm and dry
Black Bile Autumn cold and dry
Phlegm Winter cold and moist
In ancient times, the seasons were linked with the four ages of man - Youth, Manhood (Prime), Decline, and Old Age (counted in Ancient times as 0-20, 20-40, 40-60, 60-death - suggesting that ancient agricultural ages corresponded roughly to our own (so much for statins)).
Mental illness in general was derived from the concept of "black bile" - which was interestingly seen to be a perturbation of normal yellow bile from excessive heat or cold (either via environment or via intemperent passions). Black bile in its time was held to be responsible for a great number of diseases, including headaache, vertigo, paralysis, spasms, epilepsy, and other mental disturbances, to diseases of the kidney, liver, and spleen.
in this as in other cases the Greeks based their theories on observations. We know that the stool of patients suffering from bleeding gastric ulcers is black, as sometimes are the substances vomited by patients with carcinoma of the stomach. A form of malaria is still known as "blackwater fever" because the urine as a result of acute intravascular hemolysis suddenly becomes very dark, if not black� similar observations may have led to the assumption that ordinary yellow bile through corruption could become black and that this black bile caused diseases, notably� melancholy."Melancholy" is derived from ancient Greek words that, via Latin, are translated to "black bile" in English. For two thousand years, "melancholia" defined the clinical term we now call "depressive disorders" in addition to the moods and states of sadness and loss (though they were often described as "melancholy" rather than "melancholia.")
Plato felt that the blood was made of two parts, "the watery part" which was innocent, and the part that is "a secretion of black and acid bile" which is potentially malignant. He felt pathologic forms of "the humors" had the potential to wander around the body, and finding "no exit or escape" become "pent up within and mingle their own vapours with the motions of the soul."
By the time of the Middle Ages and Renaissance, variant in the Black Bile theory had come to the fore. There was not only "natural" black bile, but also "burnt black bile" derived from combustion of yellow bile in the absence of fever that provoked "violent delerium� because it occupies the substance of the brain itself." In time, the concept of unnatural black bile evolved so that the process of burning or combustion of the four humors could lead to the bitter black bile, thus it became common to think of four types of black bile derived from the four humors. The causes suggested for such a process were improper diet, physiological disorders, and immoderate passions. The burning process would lead to hot melancholy, which would be followed in turn by cold melancholy.
In ancient Western medicine, the term "non-naturals" referred to a group of environmental factors related to the disease process: 1) air, 2) exercise and rest, 3) sleep and wakefulness, 4) food and drink, 5) excretion and retention of superfluities, and 6) the passions and perturbations of the soul. For hundreds of generations, management of the patient by a physician involved addressing issues with these six factors and bringing the "whole organism" back to equilibrium. (In modern times we call the "non-naturals" model the "Biopsychosocial model" of psychiatric diagnosis.)
By the 18th and 19th centuries, the discovery of microorganisms and other issues leading to pathologic states fed into this model. Just what is disease, anyway?
Disease is the aggregate of those conditions which, judged by the prevailing culture, are deemed painful, or disabling, and which, at the same time, deviate from either the statistical norm or from some idealized status. Health, the opposite, is the state of well-being conforming to the ideals of a prevailing culture, or to the statistical norm.In a more practical sense, "disease" is "a pattern of factors which somehow hang together and recur, more or less the same, in successive individuals." The theories of causative factors have varied over the years, from perturbations of the "six non-naturals" to microbial attack to demonic possession. A symptom is something described by the suffering individual, a sign is something observed by others. A disease is a combination of anatomical, physiological, biochemical, and psychological deviations from the norm that comprise the basis of symptoms and signs.
In any event, "disease" is a deviation from the norm, something added to the healthy state to bring on illness. "Outside" element theories (such as demonic possession) dictated a treatment of removing the offending element. "Inside" element theories involved paying attention to the individual as well as the nature of the disease to best affect a cure. These theories do not differ too significantly from our models of disease and treatment today.
In all cases, disease is relative, varying from culture to culture. Some mental states are considered in all history and culture as distinctly unusual, in other cultures, the mentally ill are considered sinners, with the unusual mental states being reflections of the sins. Others have been thought of as prophets or holy men, and have been honored rather than treated.
I bring up this history because we have to understand that even our modern Western understanding of disease reflects these ancient biases. There are perturbations and demons, strength of moral fiber or lack of temperance. Add in microorganisms, character, maladaptive coping strategies, trauma, genetics, diet� we learn from history the same lessons over and over. It behooves us to listen to our ancestral nutritional and lifestyle programming. The more things change, the more things stay the same.
Kamis, 16 Juni 2011
Alrighty. You might have noticed I've slowed down on the blogging a tad this month. Well, there's sunshine and vitamin D to collect, and lots of social engagements (here in the Northeast U.S. we seem to do everything for the whole year in the summer). Also, ever since I started doing crossfit, I have needed more time to admire myself in the mirror (see Melissa's comment).
Today's music is on the� cheesy classical side. I'm feeling a little Spanish summer on the Mediterranean right now. Just go with it (as always, right click in new tab): Concerto De Aranjuez Adagio.
Paleoland events: Turns out I'm the blog of the week at Latest In Paleo! Also, "fantastic." (Surely you jest, I mean, really? Tell me more�thanks Angelo!) AND very excited that next week I will join the ranks of Stephan Guyenet, Kurt Harris, and Chris Masterjohn to participate in a Healthy Skeptic Podcast with Chris Kresser and Danny Roddy. Chris asks me to ask you if you have any questions for me. You can post them here on my blog, or if the Blogger comment system is too much of a deterrent (you are not the first - 20/20 hindsight would lead me to Wordpress�), then I'm told Chris is also going to post and you can ask a question over there. If there is something I can't answer, I will surely dodge or turn it around on you just like any practiced therapist.
Now, the Science. A new paper came out in the JAMA Archives of Neurology. The Archives are always going to be pretty much a first tier journal in any specialty, and it is important to keep abreast of them.
Here's the paper: Diet Intervention and Cerebrospinal Fluid Biomarkers in Amnestic Mild Cognitive Impairment.
The design: 20 healthy 69 y/os and 29 68 y/os with amnestic-type mild cognitive impairment were randomized to either a HIGH diet or an isocaloric LOW diet for four weeks. The HIGH diet was 45% fat (25% saturated fat), 35-40% high glycemic carbohydrates, and 15-20% protein. The LOW diet was 25% fat (7% saturated fat), 55-60% carbohydrate, and 15-20% protein. The diets were designed by a nutritionist and the food was delivered twice weekly to the participants. There is no more information about the diets, but I have emailed the corresponding author to ask for more details (um, were the deliveries kinda like Jenny Craig mirowaveable meals or whole food? Is it sugar or starch? Is the saturated fat animal fat, coconut oil? What about the trans fats? You know, all those gory but vitally important details.) All participants were free of major psychiatric or neurologic disorders other than mild cognitive impairment, and were free of kidney disease, diabetes, COPD, cardiac disease, alcoholism, and no one was on cholesterol-lowering medication (where did they find these 68 year/olds not on statins? Oh, Seattle.)
I quote: "The length of time participants consumed the HIGH diet was restricted due to safety considerations." My goodness! Safety considerations! What were they giving them? Surely not something so horrific as coconut cream or steak� well, thus far we don't know what they were giving them. I mean, I have to give the researchers huge kudos for examining diet and the brain at all! But let's have a look at the results, shall we?
The participants received cognitive testing, oral glucose tolerance testing, blood collection, and a lumbar puncture before and in the fourth week of the diet. Insulin, glucose, and blood lipids were measured, as well as CSF amyloid beta protein (a couple of types), tau protein, apolipoprotein E, and F2-isoprostanes (omega-6 derived marker of inflammation and oxidative stress).
Okay. So the HIGH diet increased insulin resistance (measured as insulin area under the curve, which is nice), and the LOW diet decreased it (far more so in the healthy controls than the mild cognitive impairment folks, which is interesting). On the HIGH diet, LDL went up by 20 points in the MCI patients and less than 10 points in the healthy controls. LDL dropped 20 points on the LOW diet in MCI folks and 15 points in the controls. Not surprisingly, HDL went down on the LOW diet (by 4 points in controls and 8 points in MCIs) and up on the HIGH diet (about 4 points for both). For some weird reason, the researchers used LDL/HDL ratio instead of the more standard total cholesterol/HDL ratio, and that went down in the LOW folks and up in the HIGH folks.
With respect to cognitive testing, everything was a wash except some mild improvement in "delayed visual memory" scores that were better on the LOW group than in the HIGH group.
In controls, CSF amyloid protein went down on the LOW group and up in the HIGH group. In the MCI folks, amyloid went up in the LOW group (which would fit the general model that amyloid beta is a last ditch desperate substitute for cholesterol in those with a dementing process going on) and remained the same in the HIGH group (the authors interpreted this as pathology was already advanced in the MCI group so dietary interventions couldn't make it much worse). CSF ApoE in controls stayed the same in the control LOW group and increase in the MCI group (again - ApoE drags cholesterol into the brain - likely to increase on a low fat diet if the brain is fat-starved) - ApoE went down in both control and MCI groups on the HIGH diet (the authors considered this to be a bad sign for the HIGH diet. I'm not so sure. If you need more ApoE, the inefficient ApoE4 will be found wanting�) CSF insulin dropped in the controls on the LOW and HIGH diets - in the MCI folks insulin increased on the LOW and stayed the same on the HIGH. Since low CSF insulin is associated with Alzheimer's, the researchers considered low insulin bad. F2-Isoprostanes decreased in both groups on the LOW diet and increased in controls on the HIGH diet (but not in MCI folks).
Yeah. I don't know what to make of it either. The authors seemed to think it was a ringing endorsement for the LOW diet. "For healthy adults, the HIGH diet moved CSF biomarkers in a direction that may characterize a presymptomatic stage of [Alzheimer's disease]� the AD biomarkers were unaffected by the HIGH diet for adults with [mild cognitive impairment], possibly because more extreme intervention is needed to exacerbate already-exant pathologic processes." And, shucks, if the HIGH diet was all industrially-fried pork rinds and chocolate cake with hydrogenated frosting, I wouldn't doubt it.
We'll see if more information comes from my email (I hope so!). Otherwise, I think this study serves as another example to show that diet is important, but that research is pointed in the direction of macronutrients rather than the quality of the food, thus we can't really make useful conclusions.
(This paper also states that cholesterol does not cross the blood brain barrier in a healthy brain - Seneff et al suggest that transcytosis of LDL across the BBB is conclusively proven in this paper.)
Read More..
Today's music is on the� cheesy classical side. I'm feeling a little Spanish summer on the Mediterranean right now. Just go with it (as always, right click in new tab): Concerto De Aranjuez Adagio.
Paleoland events: Turns out I'm the blog of the week at Latest In Paleo! Also, "fantastic." (Surely you jest, I mean, really? Tell me more�thanks Angelo!) AND very excited that next week I will join the ranks of Stephan Guyenet, Kurt Harris, and Chris Masterjohn to participate in a Healthy Skeptic Podcast with Chris Kresser and Danny Roddy. Chris asks me to ask you if you have any questions for me. You can post them here on my blog, or if the Blogger comment system is too much of a deterrent (you are not the first - 20/20 hindsight would lead me to Wordpress�), then I'm told Chris is also going to post and you can ask a question over there. If there is something I can't answer, I will surely dodge or turn it around on you just like any practiced therapist.
Now, the Science. A new paper came out in the JAMA Archives of Neurology. The Archives are always going to be pretty much a first tier journal in any specialty, and it is important to keep abreast of them.
Here's the paper: Diet Intervention and Cerebrospinal Fluid Biomarkers in Amnestic Mild Cognitive Impairment.
The design: 20 healthy 69 y/os and 29 68 y/os with amnestic-type mild cognitive impairment were randomized to either a HIGH diet or an isocaloric LOW diet for four weeks. The HIGH diet was 45% fat (25% saturated fat), 35-40% high glycemic carbohydrates, and 15-20% protein. The LOW diet was 25% fat (7% saturated fat), 55-60% carbohydrate, and 15-20% protein. The diets were designed by a nutritionist and the food was delivered twice weekly to the participants. There is no more information about the diets, but I have emailed the corresponding author to ask for more details (um, were the deliveries kinda like Jenny Craig mirowaveable meals or whole food? Is it sugar or starch? Is the saturated fat animal fat, coconut oil? What about the trans fats? You know, all those gory but vitally important details.) All participants were free of major psychiatric or neurologic disorders other than mild cognitive impairment, and were free of kidney disease, diabetes, COPD, cardiac disease, alcoholism, and no one was on cholesterol-lowering medication (where did they find these 68 year/olds not on statins? Oh, Seattle.)
I quote: "The length of time participants consumed the HIGH diet was restricted due to safety considerations." My goodness! Safety considerations! What were they giving them? Surely not something so horrific as coconut cream or steak� well, thus far we don't know what they were giving them. I mean, I have to give the researchers huge kudos for examining diet and the brain at all! But let's have a look at the results, shall we?
The participants received cognitive testing, oral glucose tolerance testing, blood collection, and a lumbar puncture before and in the fourth week of the diet. Insulin, glucose, and blood lipids were measured, as well as CSF amyloid beta protein (a couple of types), tau protein, apolipoprotein E, and F2-isoprostanes (omega-6 derived marker of inflammation and oxidative stress).
Okay. So the HIGH diet increased insulin resistance (measured as insulin area under the curve, which is nice), and the LOW diet decreased it (far more so in the healthy controls than the mild cognitive impairment folks, which is interesting). On the HIGH diet, LDL went up by 20 points in the MCI patients and less than 10 points in the healthy controls. LDL dropped 20 points on the LOW diet in MCI folks and 15 points in the controls. Not surprisingly, HDL went down on the LOW diet (by 4 points in controls and 8 points in MCIs) and up on the HIGH diet (about 4 points for both). For some weird reason, the researchers used LDL/HDL ratio instead of the more standard total cholesterol/HDL ratio, and that went down in the LOW folks and up in the HIGH folks.
With respect to cognitive testing, everything was a wash except some mild improvement in "delayed visual memory" scores that were better on the LOW group than in the HIGH group.
In controls, CSF amyloid protein went down on the LOW group and up in the HIGH group. In the MCI folks, amyloid went up in the LOW group (which would fit the general model that amyloid beta is a last ditch desperate substitute for cholesterol in those with a dementing process going on) and remained the same in the HIGH group (the authors interpreted this as pathology was already advanced in the MCI group so dietary interventions couldn't make it much worse). CSF ApoE in controls stayed the same in the control LOW group and increase in the MCI group (again - ApoE drags cholesterol into the brain - likely to increase on a low fat diet if the brain is fat-starved) - ApoE went down in both control and MCI groups on the HIGH diet (the authors considered this to be a bad sign for the HIGH diet. I'm not so sure. If you need more ApoE, the inefficient ApoE4 will be found wanting�) CSF insulin dropped in the controls on the LOW and HIGH diets - in the MCI folks insulin increased on the LOW and stayed the same on the HIGH. Since low CSF insulin is associated with Alzheimer's, the researchers considered low insulin bad. F2-Isoprostanes decreased in both groups on the LOW diet and increased in controls on the HIGH diet (but not in MCI folks).
Yeah. I don't know what to make of it either. The authors seemed to think it was a ringing endorsement for the LOW diet. "For healthy adults, the HIGH diet moved CSF biomarkers in a direction that may characterize a presymptomatic stage of [Alzheimer's disease]� the AD biomarkers were unaffected by the HIGH diet for adults with [mild cognitive impairment], possibly because more extreme intervention is needed to exacerbate already-exant pathologic processes." And, shucks, if the HIGH diet was all industrially-fried pork rinds and chocolate cake with hydrogenated frosting, I wouldn't doubt it.
We'll see if more information comes from my email (I hope so!). Otherwise, I think this study serves as another example to show that diet is important, but that research is pointed in the direction of macronutrients rather than the quality of the food, thus we can't really make useful conclusions.
(This paper also states that cholesterol does not cross the blood brain barrier in a healthy brain - Seneff et al suggest that transcytosis of LDL across the BBB is conclusively proven in this paper.)
Minggu, 12 Juni 2011
Tomorrow, June 13th, will be my one-year blogiversary. And what an exciting year it has been - especially becoming connected with the paleo blogging community. I credit the tried and true long-timers for helping my little niche nutrition and psychiatry blog become successful (and am humbled that such terrific minds could consider my blog worthy) - Stephan Guyenet is consistently my biggest referral source. Peter at Hyperlipid has given me a nod. Kurt Harris put me on his blogroll very early and is also a great referrer here (in addition he's a great person to knock around a few ideas with, and of course he helped me get my gig at Psychology Today). Melissa has mentioned my blog several times, always describing my posts as "dense" (which I find really funny, for some reason :-) ). Chris Masterjohn has also linked to me and complimented my kids, which I like! More recently, Mark Sisson asked me to do a guest post, resulting in a surge of readership. Dr. T. and Dr. BG at Nephropal had me do an early post as well. Richard has supported me on twitter, and Dr. Eades been gracious enough to link my blog several times in his comments. Andrew has linked to me on twitter and on his blog. Patrik even put one of my entries as the header at Paleohacks. So you see, with that kind of firepower helping me out, I can't help but be rocketed forward in 12 short months!
I can't possibly mention everyone - but special thanks go out of course to Jamie Scott (now surfing on volcanoes) and Paul and Shou-Ching Jaminet - all have been in the paleosphere for a bit over a year, and are great friends and referrers.
In the next few months a bunch of exciting things are coming up - including a podcast with Chris Kresser (who has also helped me out by linking to me on twitter and facebook) and the release of my podcast with Jimmy Moore. And, of course, most exciting of all is the upcoming Ancestral Health Symposium, where it looks like I'll get to meet more of my blogging buddies, and I'll present with Jamie about resiliency and human-friendly ways to cultivate it. I'll also be attending the MovNat One Day Workshop while in LA, and I am thrilled to be able to do that.
Whew. Thanks of course to all the readers and commenters and paper fairies. We're all in this together.
Oh, and I refurbished my magnesium posts for Psychology Today - so go take a look!
Magnesium and the Brain: The Original Chill Pill.
Read More..
I can't possibly mention everyone - but special thanks go out of course to Jamie Scott (now surfing on volcanoes) and Paul and Shou-Ching Jaminet - all have been in the paleosphere for a bit over a year, and are great friends and referrers.
In the next few months a bunch of exciting things are coming up - including a podcast with Chris Kresser (who has also helped me out by linking to me on twitter and facebook) and the release of my podcast with Jimmy Moore. And, of course, most exciting of all is the upcoming Ancestral Health Symposium, where it looks like I'll get to meet more of my blogging buddies, and I'll present with Jamie about resiliency and human-friendly ways to cultivate it. I'll also be attending the MovNat One Day Workshop while in LA, and I am thrilled to be able to do that.
Whew. Thanks of course to all the readers and commenters and paper fairies. We're all in this together.
Oh, and I refurbished my magnesium posts for Psychology Today - so go take a look!
Magnesium and the Brain: The Original Chill Pill.
Jumat, 10 Juni 2011
Perhaps a month ago, Zooko tweeted me some papers - one of which I had seen before. Both papers were done on the same group of obese dieters (half eating low carb and half eating an isocaloric low fat diet) for 52 weeks. Zooko presented a puzzle and links to the free full text - notice anything about the data?
Paper Number 1 (I'm adjusting the name for simplicity's sake): Low Carb vs. Low Fat - Cardiometabolic and Weight Loss Effects
Paper Number 2: Low Carb vs. Low Fat - Mood and Cognitive Function
So, have you taken a look and found the interesting thing about ketones? Yeah, Zooko had to point it out more explicitly to me as well - though to be fair I was distracted by some issues I have with the second paper's conclusions.
All right, here's the important bit. The first graph is from the first paper, showing levels of ketones in the low carb and isocaloric low fat dieters over the 12 months. (The low carb dieters were advised to increase carbs a bit after 8 weeks, which is no doubt part of why their ketones drop at that point):
Note also that both the low fat and low carb dieters have higher plasma levels of ketones in the first 8 weeks than thereafter.
Now here's a graph from the second paper, showing Beck Depression Inventory scores at the same time points (a higher score corresponds to a more depressed individual - though none of these scores are high enough to indicate even a mild depression):
Those first eight weeks, with more ketones for both sets of dieters (and since they were losing weight, ketones in the low fat group especially would have been from burning stored fat), corresponded to a 4 point drop on the BDI for both sets of dieters. I have no idea if the correlation between the two sets of data in that first 8 weeks (or later) is statistically significant, so don't run to the bank or anything - it's just rather interesting. Most obese dieters will be pretty happy to be losing weight, especially at first.
Now the distracting thing I find objectionable about the second paper is that, even though both groups had identical depression scores at baseline, 24% of the low carb group were on antidepressants compared to 12% of the low fat group at the beginning of the study. The authors discounted that bit of data somewhat, saying it was non-significant. They go on to suggest that on explanation of the low-carber's tendency to move back toward baseline levels of depression as opposed to the low fat dieters is that low-carbers are more isolated in society as the eating patterns are far from the norm.
The low-carbers were instructed to consume no more than 20% of their calories from saturated fat. That means they had to be downing a bit of olive oil or lots of PUFAs, so you do wonder about a massive omega 6 load over time. The low fat dieters, on the other hand, were consuming the palmitic acid from all the stored carbs of yore and presumably not adding as much dietary omega 6 to the party as they were instructed to eat low fat.
Cognition-wise, though the authors had found some problems with cognition measures in the low-carb group in the first 8 weeks compared to the low fat group, there was no difference between the groups after 52 weeks, suggesting the adaptation period may have led to some temporary cognitive problems in the low carb group that then resolved. ("Low carb flu?")
Personally, after 16 hours of fasting (which I am quite adapted to at this point), I find my thinking is sharper, I'm less distractible, and more motivated for the next several hours (I've never fasted longer than 24 hours). Anecdotally, others have shared the same experience.
What I'm trying to sort out here is what the ketones are doing. In order to achieve seizure control by changing oxaloacetate concentrations with a ketogenic diet, you need to be in pretty deep ketosis and it would take more than a 16 hour fast to get there. Glucose is preferentially sucked up in the brain as it is the last place in the body to become "insulin resistant" in starvation or high-fat conditions. While some folks seem to love deep ketosis and thrive there, I have always wondered if the more evolutionary model of intermittent fasting (though there may have been high fat seasons also) would have a beneficial effect via ketones, despite the fact that most IFing does not leave us in ketosis deep enough or long enough to change the amino acid handling in the brain in a way that lowers seizure threshold.
In cells of the brain with mitochondria, I'm still assuming one would get boosts in energy efficiency from partial utilization of ketones, as I've discussed before.
There's a lot to sort out and a gazillion variables, but I thought the graphs were cool enough to put them out there for your perusal. Thanks Zooko!
Here's the weight loss, in case you were interested:
(While we are discussing ketones, Zooko also tweeted news that a young man who started a ketogenic diet after being diagnosed with brain cancer is now in remission. Happy news indeed! Zooko noted in a later tweet that we can't know the ketogenic diet helped bring on remission, but it is certainly plausible that it may have helped.)
Read More..
Paper Number 1 (I'm adjusting the name for simplicity's sake): Low Carb vs. Low Fat - Cardiometabolic and Weight Loss Effects
Paper Number 2: Low Carb vs. Low Fat - Mood and Cognitive Function
So, have you taken a look and found the interesting thing about ketones? Yeah, Zooko had to point it out more explicitly to me as well - though to be fair I was distracted by some issues I have with the second paper's conclusions.
All right, here's the important bit. The first graph is from the first paper, showing levels of ketones in the low carb and isocaloric low fat dieters over the 12 months. (The low carb dieters were advised to increase carbs a bit after 8 weeks, which is no doubt part of why their ketones drop at that point):
Note also that both the low fat and low carb dieters have higher plasma levels of ketones in the first 8 weeks than thereafter.
Now here's a graph from the second paper, showing Beck Depression Inventory scores at the same time points (a higher score corresponds to a more depressed individual - though none of these scores are high enough to indicate even a mild depression):
Those first eight weeks, with more ketones for both sets of dieters (and since they were losing weight, ketones in the low fat group especially would have been from burning stored fat), corresponded to a 4 point drop on the BDI for both sets of dieters. I have no idea if the correlation between the two sets of data in that first 8 weeks (or later) is statistically significant, so don't run to the bank or anything - it's just rather interesting. Most obese dieters will be pretty happy to be losing weight, especially at first.
Now the distracting thing I find objectionable about the second paper is that, even though both groups had identical depression scores at baseline, 24% of the low carb group were on antidepressants compared to 12% of the low fat group at the beginning of the study. The authors discounted that bit of data somewhat, saying it was non-significant. They go on to suggest that on explanation of the low-carber's tendency to move back toward baseline levels of depression as opposed to the low fat dieters is that low-carbers are more isolated in society as the eating patterns are far from the norm.
The low-carbers were instructed to consume no more than 20% of their calories from saturated fat. That means they had to be downing a bit of olive oil or lots of PUFAs, so you do wonder about a massive omega 6 load over time. The low fat dieters, on the other hand, were consuming the palmitic acid from all the stored carbs of yore and presumably not adding as much dietary omega 6 to the party as they were instructed to eat low fat.
Cognition-wise, though the authors had found some problems with cognition measures in the low-carb group in the first 8 weeks compared to the low fat group, there was no difference between the groups after 52 weeks, suggesting the adaptation period may have led to some temporary cognitive problems in the low carb group that then resolved. ("Low carb flu?")
Personally, after 16 hours of fasting (which I am quite adapted to at this point), I find my thinking is sharper, I'm less distractible, and more motivated for the next several hours (I've never fasted longer than 24 hours). Anecdotally, others have shared the same experience.
What I'm trying to sort out here is what the ketones are doing. In order to achieve seizure control by changing oxaloacetate concentrations with a ketogenic diet, you need to be in pretty deep ketosis and it would take more than a 16 hour fast to get there. Glucose is preferentially sucked up in the brain as it is the last place in the body to become "insulin resistant" in starvation or high-fat conditions. While some folks seem to love deep ketosis and thrive there, I have always wondered if the more evolutionary model of intermittent fasting (though there may have been high fat seasons also) would have a beneficial effect via ketones, despite the fact that most IFing does not leave us in ketosis deep enough or long enough to change the amino acid handling in the brain in a way that lowers seizure threshold.
In cells of the brain with mitochondria, I'm still assuming one would get boosts in energy efficiency from partial utilization of ketones, as I've discussed before.
There's a lot to sort out and a gazillion variables, but I thought the graphs were cool enough to put them out there for your perusal. Thanks Zooko!
Here's the weight loss, in case you were interested:
(While we are discussing ketones, Zooko also tweeted news that a young man who started a ketogenic diet after being diagnosed with brain cancer is now in remission. Happy news indeed! Zooko noted in a later tweet that we can't know the ketogenic diet helped bring on remission, but it is certainly plausible that it may have helped.)
Minggu, 05 Juni 2011
It's a lovely Sunday here and I'm actually beginning to sport a bit of a tan (remarkably enough) - we're inside for lunch and naps (the kids, sadly, not mine) and I thought I would take a moment to link to my brand new exclusive Psychology Today article, Brain Food, which tells you what I ate for two meals, and also where I get my vegetables. Here's today's menu:
Breakfast: Farmer's market bacon, mustard greens, kale (yuck - always seems like a punishment, even chopped fine and sauteed in bacon grease), half a banana
Head to playground, where youngest (who in the morning exhibited remarkable throwing capacity by beaning me in the head with a sippy cup full of milk) manages to nearly fling herself off every piece of playground equipment. Oldest is afraid of heights and there's no worrying with her, except it would be nice to see her to attempt ladders and monkey bars before youngest does.
Lunch: not hungry - (kids eat leftover fried rice)
While kids nap: 1, er, I mean 2, glasses pinot noir whilst sitting in sun on the back deck.
Dinner: Crockpot beef stew - beef stock (simmered in crockpot for about four hours with beef tendon, radish and turnip greens and green garlic) - remove the stock veggies, add one onion, two peeled potatoes, splash of Worcestershire sauce, chopped green garlic, two pounds grassfed top round. Crockpot for a couple of hours, then add chopped kale, young turnips, and a baby bok choy. Crockpot another couple of hours. Add salt and pepper and Tabasco to taste. We'll see how it turns out in a few hours. Might need to add soy sauce (my coconut aminos fermented and is no longer palatable - that's some amazing but fragile stuff. Refrigerate and use quickly) or red wine. We'll see.
Up next: A while back Zooko highlighted some papers about ketones and depression which I hope to cover. Also, I really want to look more closely at our good friend folate.
All right, back to mom work...
Read More..
Breakfast: Farmer's market bacon, mustard greens, kale (yuck - always seems like a punishment, even chopped fine and sauteed in bacon grease), half a banana
Head to playground, where youngest (who in the morning exhibited remarkable throwing capacity by beaning me in the head with a sippy cup full of milk) manages to nearly fling herself off every piece of playground equipment. Oldest is afraid of heights and there's no worrying with her, except it would be nice to see her to attempt ladders and monkey bars before youngest does.
Lunch: not hungry - (kids eat leftover fried rice)
While kids nap: 1, er, I mean 2, glasses pinot noir whilst sitting in sun on the back deck.
Dinner: Crockpot beef stew - beef stock (simmered in crockpot for about four hours with beef tendon, radish and turnip greens and green garlic) - remove the stock veggies, add one onion, two peeled potatoes, splash of Worcestershire sauce, chopped green garlic, two pounds grassfed top round. Crockpot for a couple of hours, then add chopped kale, young turnips, and a baby bok choy. Crockpot another couple of hours. Add salt and pepper and Tabasco to taste. We'll see how it turns out in a few hours. Might need to add soy sauce (my coconut aminos fermented and is no longer palatable - that's some amazing but fragile stuff. Refrigerate and use quickly) or red wine. We'll see.
Up next: A while back Zooko highlighted some papers about ketones and depression which I hope to cover. Also, I really want to look more closely at our good friend folate.
All right, back to mom work...
Jumat, 03 Juni 2011
First off I wanted to link to my latest podcast; this one is with Michael Ostrolenk at the Voices For Hope Podcast. I had a great time talking to Michael, and we managed to squeeze a lot of me talking in the lean 17 minute interview. It's funny - since in my line of work I typically do a lot of the listening, sometimes when people ask me questions I can really get going�
Evolutionary Psychiatry at Voices For Hope
Thanks Michael!
And now onto the gentlemanly duel of mild-mannered, gorgeously-referenced, thoughtful posts between Stephan Guyenet and the Jaminets at Perfect Health Diet - if "food reward" is a dominant factor in obesity, should we be eating a new brand of "bland" paleo? Is obesity regulation in the brain, the liver, the adipose tissue, or the gut?
I will approach the question(s) a bit from the hip and from a clinical perspective, focusing on the far end of the food reward and obesity spectrum (which certainly will not describe all those who are obese) - the binge eaters. For a little (referenced) perspective on the neurobiology of binge eating, read my posts here and here.
So� what do I like about the "food reward" theory of obesity - (in the briefest of nutshells, the idea that constant exposure to overly palatable food overwhelms our natural feedback mechanisms and causes us to overeat)? This theory is brain-centric, and I'm a brain-centric sort of person. It is similar to addiction (and involves many of the same neurotransmitters and brain areas) - an addiction is also tough (or impossible) to shake, involves inflammation as part of the brain pathology, and seems to afflict people along genetic lines. Some folks can shoot up a bit of heroin, for example, and never feel the urge again, while others get a prescription for percocet after a work-league softball injury and are off to the races, snorting oxycontin and spending $300 bucks a day. The numbers for addiction and dieting are comparable - quitting smoking cold turkey, for example, has somewhere around a 5-12% success rate long term. Any and all diets seem to be similar - 95% of people regain the weight within 5 years.
The treatment for addiction is to abstain, one way or another. A certain percentage of alcoholics can, one day, go back to moderate drinking, but some will never be able to touch alcohol again or end up back in the sober house without driver's license, job, or family - even 15 or 20 years into sobriety. If "food reward" is a problem of overly palatable food, then the solution seems to be to go bland. A compelling argument, really, and seems nicely in line with an Eastern philosophy of striving towards the state of wanting nothing. Kessler in The End of Overeating: Taking Control of the Insatiable American Appetite
calls the sugar/fat/salt combo in industrial, processed, and restaurant food "hyperpalatable" - and for him the solution is "food rehab" - abstaining and developing a sense of disgust about that sort of food.
The Jaminets are concerned that our brains have a food reward system for a reason - succulent lovely amazing fruit and bone marrow and drippy yummity steak are highly nutritious and good for us. Should we be deliberately trying to go bland in the name of dropping pounds?
Here's where my clinical brain and experience with patients gets involved. I've talked to a lot of people struggling with addiction over the years, and a lot of people struggling with binge eating, bulimia, or some variation in between. And, I have to say, the struggles and cravings and relapses and descriptions people relate to me about their bingeing have very similar flavors, whether you are bingeing on Little Debbies, Taco Bell, or Jack Daniels.
There's a love affair with the food or drug - thinking about it, craving it, desiring it, then a shift into automaton binge so that the lead-up is typically far more pleasurable than the actual event. And always along for the ride comes some sort of awfulness, even putting aside the guilt and recrimination. Often when people shoot up heroin for the first time, they vomit. Cigarette smoke - it's nasty, you cough, you smell - it's unpleasant. Cocaine stings the nose and leads to sudden euphoria followed by a much longer period of irritability and depression. And, for the most part, the food that humans typically binge on is.. well� kinda nasty (seriously, look at that bag of creamsicle oreos in that link to Melissa's blog!). It's too sweet, has crappy texture, smells of chemicals - it's Taco Bell meat "product" or rancid oily Pringles or gut-bursting amounts of slippery pasta. For most people (including myself), those healthy, magnesium and copper containing richly flavored low in O6 bars of 85% dark chocolate (intense, addicting chocolate) can be lovingly divided and savored over a week or two - but if I buy the toffee version (34% cacao, milk chocolate) I have to divide it with my kids or I will easily gobble down the whole bar and end up with a sickly feeling and a tummy ache.
So I don't know that straight-up palatability is the end all be all - though Stephan's experiments in treating obesity with low-reward food that he references are fascinating, and he might well prove me wrong. I think the similarity between the hyperpalatable industrial food and the hard drugs is that they are all (somewhat metaphorically) poisons, but we take the dose anyway, and need bigger and bigger amounts.
So far as obesity - and now I'm talking about the general problem, not just the subsection of serious binge eaters and subclinical versions of that - I think that in some people, the problem is in genetic vulnerabilities in the reward system in the brain. In others, it's a methylation problem in the liver. In others, and issue with gut flora. Or combinations of all of the above, and many other things I'm certainly not an expert in. All the pieces are related, all could affect the ultimate downstream leptin areas in our noggins. So perhaps some folks will need to go bland, or at least do so for a while as the inflammation goes down. Others can dive into the bone marrow salad dressing, eat nectarines dripping with juice, and use the pepper with gusto.
These are my speculations. Take them as you will.
Read More..
Evolutionary Psychiatry at Voices For Hope
Thanks Michael!
And now onto the gentlemanly duel of mild-mannered, gorgeously-referenced, thoughtful posts between Stephan Guyenet and the Jaminets at Perfect Health Diet - if "food reward" is a dominant factor in obesity, should we be eating a new brand of "bland" paleo? Is obesity regulation in the brain, the liver, the adipose tissue, or the gut?
I will approach the question(s) a bit from the hip and from a clinical perspective, focusing on the far end of the food reward and obesity spectrum (which certainly will not describe all those who are obese) - the binge eaters. For a little (referenced) perspective on the neurobiology of binge eating, read my posts here and here.
So� what do I like about the "food reward" theory of obesity - (in the briefest of nutshells, the idea that constant exposure to overly palatable food overwhelms our natural feedback mechanisms and causes us to overeat)? This theory is brain-centric, and I'm a brain-centric sort of person. It is similar to addiction (and involves many of the same neurotransmitters and brain areas) - an addiction is also tough (or impossible) to shake, involves inflammation as part of the brain pathology, and seems to afflict people along genetic lines. Some folks can shoot up a bit of heroin, for example, and never feel the urge again, while others get a prescription for percocet after a work-league softball injury and are off to the races, snorting oxycontin and spending $300 bucks a day. The numbers for addiction and dieting are comparable - quitting smoking cold turkey, for example, has somewhere around a 5-12% success rate long term. Any and all diets seem to be similar - 95% of people regain the weight within 5 years.
The treatment for addiction is to abstain, one way or another. A certain percentage of alcoholics can, one day, go back to moderate drinking, but some will never be able to touch alcohol again or end up back in the sober house without driver's license, job, or family - even 15 or 20 years into sobriety. If "food reward" is a problem of overly palatable food, then the solution seems to be to go bland. A compelling argument, really, and seems nicely in line with an Eastern philosophy of striving towards the state of wanting nothing. Kessler in The End of Overeating: Taking Control of the Insatiable American Appetite
calls the sugar/fat/salt combo in industrial, processed, and restaurant food "hyperpalatable" - and for him the solution is "food rehab" - abstaining and developing a sense of disgust about that sort of food. The Jaminets are concerned that our brains have a food reward system for a reason - succulent lovely amazing fruit and bone marrow and drippy yummity steak are highly nutritious and good for us. Should we be deliberately trying to go bland in the name of dropping pounds?
Here's where my clinical brain and experience with patients gets involved. I've talked to a lot of people struggling with addiction over the years, and a lot of people struggling with binge eating, bulimia, or some variation in between. And, I have to say, the struggles and cravings and relapses and descriptions people relate to me about their bingeing have very similar flavors, whether you are bingeing on Little Debbies, Taco Bell, or Jack Daniels.
There's a love affair with the food or drug - thinking about it, craving it, desiring it, then a shift into automaton binge so that the lead-up is typically far more pleasurable than the actual event. And always along for the ride comes some sort of awfulness, even putting aside the guilt and recrimination. Often when people shoot up heroin for the first time, they vomit. Cigarette smoke - it's nasty, you cough, you smell - it's unpleasant. Cocaine stings the nose and leads to sudden euphoria followed by a much longer period of irritability and depression. And, for the most part, the food that humans typically binge on is.. well� kinda nasty (seriously, look at that bag of creamsicle oreos in that link to Melissa's blog!). It's too sweet, has crappy texture, smells of chemicals - it's Taco Bell meat "product" or rancid oily Pringles or gut-bursting amounts of slippery pasta. For most people (including myself), those healthy, magnesium and copper containing richly flavored low in O6 bars of 85% dark chocolate (intense, addicting chocolate) can be lovingly divided and savored over a week or two - but if I buy the toffee version (34% cacao, milk chocolate) I have to divide it with my kids or I will easily gobble down the whole bar and end up with a sickly feeling and a tummy ache.
So I don't know that straight-up palatability is the end all be all - though Stephan's experiments in treating obesity with low-reward food that he references are fascinating, and he might well prove me wrong. I think the similarity between the hyperpalatable industrial food and the hard drugs is that they are all (somewhat metaphorically) poisons, but we take the dose anyway, and need bigger and bigger amounts.
So far as obesity - and now I'm talking about the general problem, not just the subsection of serious binge eaters and subclinical versions of that - I think that in some people, the problem is in genetic vulnerabilities in the reward system in the brain. In others, it's a methylation problem in the liver. In others, and issue with gut flora. Or combinations of all of the above, and many other things I'm certainly not an expert in. All the pieces are related, all could affect the ultimate downstream leptin areas in our noggins. So perhaps some folks will need to go bland, or at least do so for a while as the inflammation goes down. Others can dive into the bone marrow salad dressing, eat nectarines dripping with juice, and use the pepper with gusto.
These are my speculations. Take them as you will.
Rabu, 01 Juni 2011
A paper by MIT's own engineer Stephanie Seneff and (as near as I can tell) a couple of medical research-reading renegades was published in the European Journal of Internal Medicine earlier this year. It is remarkable to see (one presumes) a major European biomedical journal publish something from outsiders. More amazing still is the easily understandable, well-referenced and cogent understanding of lipoproteins, metabolism, and brain chemistry. In our specialty journals we often get shallow papers that peck at a single organ system, without a holistic understanding of physiology.
So with no further ado - let's dive in. I'm going to summarize the best bits of the paper, but I strongly encourage you to read the paper for yourself - the link above is to a full-text version available at Seneff's own website at MIT. Alzheimer's dementia is a disease I've blogged about before extensively, a degenerative disease characterized by nerve cell death, plaques and tangles, and linked with insulin resistance, diabetes, and� low cholesterol.
Millions of dollars and several decades have been spent chasing down the most obvious pathology - those plaques and tangles. We innovative humans have invented all sorts of marvelously clever treatments - including vaccines against plaque, and drugs that interfere with plaque synthesis. The problems is the vaccines did no good, and the trials for the plaque-busting drug was halted early due to an obvious "accelerated deterioration in cognition in the treatment group compared to placebo-based controls."
It seems the typical response to such failures is to think - oh, we aren't acting early enough or we aren't busting up enough plaques - which might be the case. Or, as Seneff and crew suggest quite astutely, the amyloid beta proteins that form the plaques might just be there for a good reason, a protective reason, and that's why they cover the Alzheimer's brain with such ferocity.
We know that there is a strong correlation between insulin resistance and early Alzheimer's, and also there is an association between mitochondrial dysfunction (particularly in complex 1) and Alzheimer's. As I discussed in Basic Science: Energy is Everything and Brain Efficiency, when the mitochondria aren't happy, your brain isn't happy. Mitochondrial dysfunction is also implicated in Parkinson's Disease and ALS, both long-term and ultimately fatal degenerative conditions.
And now, a point I've made before (in Low Cholesterol and Suicide)- the brain is relatively small, but has 25% of the body's cholesterol. Cholesterol insulates neurons as part of the myelin sheath and provides the scaffold for the neural network, and is an important part of the membranes and all synapses. While much of the cholesterol used in the brain is made in the brain, there is clear evidence that apolipoprotein E (ApoE) is a big player in the game of shuttling cholesterol, fat, and antioxidants to the central nervous system from the body's main cholesterol factory, the liver. ApoE is made in nerve cells called astrocytes (who tend to and feed neurons), and ApoE allows the astrocytes to suck lipids, antioxidants, and cholesterol arriving in LDL and IDL particles from the bloodstream. Yes, astrocytes can transport LDL across the blood brain barrier.
The biggest genetic risk for Alzheimer's is being a carrier of a certain type of ApoE gene called ApoE4. Research has shown that ApoE4 is associated with reduced cholesterol uptake by the astrocytes. What has been confusing for the lipophobic medical establishment is that ApoE4 is associated with high LDL cholesterol� so it must be that nasty horrible LDL killing the brain! But the key bit to understand is that LDL cholesterol in longitudinal studies tends to drop before the development of Alzheimer's disease. Hmmm. We can't ignore the following tantalizing clue either:
These sick neurons do their darndest to go forward despite the growing burden of oxidative damage and smokey, spewing mitochondria - until the end, when they are so damaged the only thing to do is to call in the immune system to send self-destruct signals. And here is where those amyloid beta proteins come in - they are hypothesized to try to stand in for cholesterol and to help shift the cell from using the damaged mitochondria to utilizing different sources in the cell cytoplasm to make energy (for the biochem nerds - specifically glucose is redirected to the pentose shunt, an anaerobic pathway generating NADPH which also can protect the cell from oxidation). Their purpose, then, is to reduce the ongoing damage as a last stand prior to self-destruction of the neurons. When the cells ultimately give up the ghost, the defensive forces are left in place, crystallize, and form the famous plaques. As Seneff so elegantly puts it: "A legacy of complex protein debris is left in place."
Back to insulin resistance and hyperglycemia, the legacy in turn of our processed carbohydrate, inflammatory, fructose-intensive Western diets - turns out the same apolipoproteins that are critical to the functioning of our cholesterol machinery are also particularly vulnerable to damage called glycation in a high-glucose environment. Glycation is known to disturb the uptake of ApoE by the astrocytes (that first step in processing cholesterol used by the brain). Diabetics with Apo-E4 are at higher risk for Alzheimer's, and it is thought that the less efficient ApoE4 combined with the detrimental effects of glycation could be the reason.
Enter the ketogenic diet, which in a pilot study has been found to be therapuetic for Alzheimers. It involves an extremely high fat diet, supplying plenty for the brain, and results in the brain being able to use alternative energy sources (ketones) that skip the damaged mitochondrial complex 1. It will also tend to lower insulin resistance and eliminate glycation, as blood sugar will be low.
And then enter the pathogens - with excess glucose and advanced glycolation end-products floating around in the blood, diabetics are more vulnerable to bacterial infection than the average person. Alzheimer's Dementia is also associated with infection with certain chronic pathogens, including H. pylori and Chlamydia pneumoniae. There are plausible mechanisms by which these infections increase inflammation and oxidative damage, hastening the onset of dementia.
What have we learned? Don't eat processed carbs, ketones and fat are our friends, avoid inflammation and foster your immune system's resistance to infection to protect your brain.
What is the scariest scenario? Well, all the diabetics. They are at higher risk for heart disease, and in the US at least they are very aggressively statinized, especially in the last 10 years. It would be considered malpractice for a primary care doc or cardiologist not to encourage statin use in a diabetic with a whiff of high cholesterol. But it seems quite plausible that drastically reducing cholesterol in combination with the hyperglycemia of diabetes is the perfect storm for developing Alzheimer's.
Dr. Steve Parker noted a study that showed no increase in Alzheimer's in autopsies of diabetics. The study was done in Japan between 1998 and 2003, and is strong evidence against the fact that plain old type II diabetes would cause Alzheimer's. In Japan there is, in general, lower cholesterol levels, and in Japanese low cholesterol is known to coincide with stroke risk. In addition, this study was done mostly before the mainstream statin explosion in the United States, anyway. I don't know how aggressively the Japanese diabetics are "treated" for high cholesterol. I wonder if the differences in the processed food burden along with cholesterol-lowering drugs explain the difference between the strong epidemiological evidence linking insulin resistance and diabetes to Alzheimer's in the Western world and the lack of relationship between diabetes and Alzheimer's in the Japanese study.
Well, we better figure it out soon. Dementia is growing, expected to triple in the next 40 years - if we don't figure it out. I'm gonna go eat some coconut oil.
Read More..
So with no further ado - let's dive in. I'm going to summarize the best bits of the paper, but I strongly encourage you to read the paper for yourself - the link above is to a full-text version available at Seneff's own website at MIT. Alzheimer's dementia is a disease I've blogged about before extensively, a degenerative disease characterized by nerve cell death, plaques and tangles, and linked with insulin resistance, diabetes, and� low cholesterol.
Millions of dollars and several decades have been spent chasing down the most obvious pathology - those plaques and tangles. We innovative humans have invented all sorts of marvelously clever treatments - including vaccines against plaque, and drugs that interfere with plaque synthesis. The problems is the vaccines did no good, and the trials for the plaque-busting drug was halted early due to an obvious "accelerated deterioration in cognition in the treatment group compared to placebo-based controls."
It seems the typical response to such failures is to think - oh, we aren't acting early enough or we aren't busting up enough plaques - which might be the case. Or, as Seneff and crew suggest quite astutely, the amyloid beta proteins that form the plaques might just be there for a good reason, a protective reason, and that's why they cover the Alzheimer's brain with such ferocity.
We know that there is a strong correlation between insulin resistance and early Alzheimer's, and also there is an association between mitochondrial dysfunction (particularly in complex 1) and Alzheimer's. As I discussed in Basic Science: Energy is Everything and Brain Efficiency, when the mitochondria aren't happy, your brain isn't happy. Mitochondrial dysfunction is also implicated in Parkinson's Disease and ALS, both long-term and ultimately fatal degenerative conditions.
And now, a point I've made before (in Low Cholesterol and Suicide)- the brain is relatively small, but has 25% of the body's cholesterol. Cholesterol insulates neurons as part of the myelin sheath and provides the scaffold for the neural network, and is an important part of the membranes and all synapses. While much of the cholesterol used in the brain is made in the brain, there is clear evidence that apolipoprotein E (ApoE) is a big player in the game of shuttling cholesterol, fat, and antioxidants to the central nervous system from the body's main cholesterol factory, the liver. ApoE is made in nerve cells called astrocytes (who tend to and feed neurons), and ApoE allows the astrocytes to suck lipids, antioxidants, and cholesterol arriving in LDL and IDL particles from the bloodstream. Yes, astrocytes can transport LDL across the blood brain barrier.
The biggest genetic risk for Alzheimer's is being a carrier of a certain type of ApoE gene called ApoE4. Research has shown that ApoE4 is associated with reduced cholesterol uptake by the astrocytes. What has been confusing for the lipophobic medical establishment is that ApoE4 is associated with high LDL cholesterol� so it must be that nasty horrible LDL killing the brain! But the key bit to understand is that LDL cholesterol in longitudinal studies tends to drop before the development of Alzheimer's disease. Hmmm. We can't ignore the following tantalizing clue either:
�high cholesterol level is positively correlated with longevity in people over 85 years old, and in some cases has been shown to be associated with better memory function and reduced dementia� the cerebrospinal fluid of [Alzheimer's Disease] patients is substantially depleted in lipoproteins, cholesterol, triglycerides, and free fatty acids compared to matched controls.All of us, but especially readers of a since-removed blog post that was part of the Venus-gate paleo disruption of a few weeks ago about the supposed dangers of densely packed saturated fat should have an understanding of how lipoproteins work. Lipoproteins (such as HDL, LDL, chylomicrons, and VLDL) basically look like this:
 |
| Image from Wikipedia |
Lipoproteins carry fats and other delicacies through the blood. The blood is dangerous and filled with nasty things like oxygen and iron that can break down our gentle fats. We don't want our fats oxidized - so the lipoproteins tuck the fats into the inside to keep them safe and snuggly. Again, a MAJOR REASON for the particular structure of lipoproteins is to keep those fats safe and not exposed to the blood. Once fats are delivered to cell membranes, we still want to keep them safe - and cholesterol is like a bit of plate armor - it helps the fats stack more tightly, protecting them from oxidative damage and invading microbial pathogens.
Seneff et al continue to stack the evidence in their paper - dietary avoidance of fat (replaced by carbohydrate) and the increasingly zealous prescriptions for cholesterol-lowering medication has coincided with the rise in Alzheimer's Dementia and diabetes and obesity. These are only correlations, but one might consider that to be some evidence in favor of the plausible hypothesis that stripping the brain of cholesterol especially in an oxidative, hyperglycemic environment could lead to very sick neurons.
These sick neurons do their darndest to go forward despite the growing burden of oxidative damage and smokey, spewing mitochondria - until the end, when they are so damaged the only thing to do is to call in the immune system to send self-destruct signals. And here is where those amyloid beta proteins come in - they are hypothesized to try to stand in for cholesterol and to help shift the cell from using the damaged mitochondria to utilizing different sources in the cell cytoplasm to make energy (for the biochem nerds - specifically glucose is redirected to the pentose shunt, an anaerobic pathway generating NADPH which also can protect the cell from oxidation). Their purpose, then, is to reduce the ongoing damage as a last stand prior to self-destruction of the neurons. When the cells ultimately give up the ghost, the defensive forces are left in place, crystallize, and form the famous plaques. As Seneff so elegantly puts it: "A legacy of complex protein debris is left in place."
Back to insulin resistance and hyperglycemia, the legacy in turn of our processed carbohydrate, inflammatory, fructose-intensive Western diets - turns out the same apolipoproteins that are critical to the functioning of our cholesterol machinery are also particularly vulnerable to damage called glycation in a high-glucose environment. Glycation is known to disturb the uptake of ApoE by the astrocytes (that first step in processing cholesterol used by the brain). Diabetics with Apo-E4 are at higher risk for Alzheimer's, and it is thought that the less efficient ApoE4 combined with the detrimental effects of glycation could be the reason.
Enter the ketogenic diet, which in a pilot study has been found to be therapuetic for Alzheimers. It involves an extremely high fat diet, supplying plenty for the brain, and results in the brain being able to use alternative energy sources (ketones) that skip the damaged mitochondrial complex 1. It will also tend to lower insulin resistance and eliminate glycation, as blood sugar will be low.
And then enter the pathogens - with excess glucose and advanced glycolation end-products floating around in the blood, diabetics are more vulnerable to bacterial infection than the average person. Alzheimer's Dementia is also associated with infection with certain chronic pathogens, including H. pylori and Chlamydia pneumoniae. There are plausible mechanisms by which these infections increase inflammation and oxidative damage, hastening the onset of dementia.
What have we learned? Don't eat processed carbs, ketones and fat are our friends, avoid inflammation and foster your immune system's resistance to infection to protect your brain.
What is the scariest scenario? Well, all the diabetics. They are at higher risk for heart disease, and in the US at least they are very aggressively statinized, especially in the last 10 years. It would be considered malpractice for a primary care doc or cardiologist not to encourage statin use in a diabetic with a whiff of high cholesterol. But it seems quite plausible that drastically reducing cholesterol in combination with the hyperglycemia of diabetes is the perfect storm for developing Alzheimer's.
Dr. Steve Parker noted a study that showed no increase in Alzheimer's in autopsies of diabetics. The study was done in Japan between 1998 and 2003, and is strong evidence against the fact that plain old type II diabetes would cause Alzheimer's. In Japan there is, in general, lower cholesterol levels, and in Japanese low cholesterol is known to coincide with stroke risk. In addition, this study was done mostly before the mainstream statin explosion in the United States, anyway. I don't know how aggressively the Japanese diabetics are "treated" for high cholesterol. I wonder if the differences in the processed food burden along with cholesterol-lowering drugs explain the difference between the strong epidemiological evidence linking insulin resistance and diabetes to Alzheimer's in the Western world and the lack of relationship between diabetes and Alzheimer's in the Japanese study.
Well, we better figure it out soon. Dementia is growing, expected to triple in the next 40 years - if we don't figure it out. I'm gonna go eat some coconut oil.
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