As I said before on this blog, I am yet to be convinced that grilled meat is truly unhealthy in the absence of leaky gut problems. I am referring here to high heat cooking-induced Maillard reactions (browning) and the resulting advanced glycation endproducts (AGEs). Whenever you cook a food in high heat, to the point of browning it, you generate a Maillard reaction. Searing and roasting meat usually leads to that.
Elevated levels of serum AGEs presumably accelerate the aging process in humans. This is supported by research with uncontrolled diabetics, who seem to have elevated levels of serum AGEs. In fact, a widely used measure in the treatment of diabetes, the HbA1c (or percentage of glycated hemoglobin), is actually a measure of endogenous AGE formation. (Endogenous = generated by our own bodies.)
Still, evidence that a person with an uncompromised gut can cause serum levels of AGEs to go up significantly by eating AGEs is weak, and evidence that any related serum AGE increases lead the average person to develop health problems is pretty much nonexistent. The human body can handle AGEs, as long as their concentration is not too high. We cannot forget that a healthy HbA1c in humans is about 5 percent; meaning that AGEs are created and dealt with by our bodies. A healthy HbA1c in humans is not 0 percent.
Thanks again to Justin for sending me the full text version of the Birlouez-Aragon et al. (2010) article, which is partially reviewed here. See this post and the comments under it for some background on this discussion. The article is unequivocally titled: “A diet based on high-heat-treated foods promotes risk factors for diabetes mellitus and cardiovascular diseases.”
This article is recent, and has already been cited by news agencies and bloggers as providing “definitive” evidence that high-heat cooking is bad for one’s health. Interestingly, quite a few of those citations are in connection with high-heat cooking of meat, which is not even the focus of the article.
In fact, the Birlouez-Aragon et al. (2010) article provides no evidence that high-heat cooking of meat leads to AGEing in humans. If anything, the article points at the use of industrial vegetable oils for cooking as the main problem. And we know already that industrial vegetable oils are not healthy, whether you cook with them or drink them cold by the tablespoon.
But there are a number of good things about this article. For example, the authors summarize past research on AGEs. They focus on MRPs, which are “Maillard reaction products”. One of the summary statements supports what I have said on this blog before:
"The few human intervention trials […] that reported on health effects of dietary MRPs have all focused on patients with diabetes or renal failure."
That is, there is no evidence from human studies that dietary AGEs cause health problems outside the context of preexisting conditions that themselves seem to be associated with endogenous AGE production. To that I would add that gut permeability may also be a problem, as in celiacs ingesting large amounts of AGEs.
As you can see from the quote below, the authors decided to focus their investigation on a particular type of AGE, namely CML or carboxymethyllysine.
"...we decided to specifically quantify CML, as a well-accepted MRP indicator ..."
As I noted in my comments under this post (the oven roasted pork tenderloin post), one particular type of diet seems to lead to high serum CML levels – a vegetarian diet.
So let us see what the authors studied:
"... we conducted a randomized, crossover, intervention trial to clarify whether a habitual diet containing high-heat-treated foods, such as deep-fried potatoes, cookies, brown crusted bread, or fried meat, could promote risk factors of type 2 diabetes or cardiovascular diseases in healthy people."
Well, “deep-fried potatoes” is a red flag, don’t you think? They don’t say what oil was used for deep-frying, but I bet it was not coconut or olive oil. Cheap industrial vegetable oils (corn, safflower etc.) are the ones normally used (and re-used) for deep-frying. This is in part because these oils are cheap, and in part because they have high “smoke points” (the temperature at which the oil begins to generate smoke).
Let us see what else the authors say about the dietary conditions they compared:
"The STD was prepared by using conventional techniques such as grilling, frying, and roasting and contained industrial food known to be highly cooked, such as extruded corn flakes, coffee, dry cookies, and well-baked bread with brown crust. In contrast, the STMD comprised some raw food and foods that were cooked with steam techniques only. In addition, convenience products were chosen according to the minimal process applied (ie, steamed corn flakes, tea, sponge cakes, and mildly baked bread) ..."
The STD diet was the one with high-heat preparation of foods; in the STMD diet the foods were all steam-cooked at relatively low temperatures. Clearly these diets were mostly of plant-based foods, and of the unhealthy kind!
The following quote, from the results, pretty much tells us that the high omega-6 content of industrial oils used for deep frying was likely to be a major confounder, if not the main culprit:
"... substantial differences in the plasma fatty acid profile with higher plasma concentrations of long-chain omega-3 fatty acids […] and lower concentrations of omega-6 fatty acids […] were analyzed in the STMD group compared with in the STD group."
That is, the high-heat cooking group had higher plasma concentrations of omega-6 fats, which is what you would expect from a group consuming a large amount of industrial vegetable oils. One single tablespoon per day is already a large amount; these folks were probably consuming more than that.
Perhaps a better title for this study would have been: “A diet based on foods deep-fried in industrial vegetable oils promotes risk factors for diabetes mellitus and cardiovascular diseases.”
This study doesn’t even get close to indicting charred meat as a major source of serum AGEs. But it is not an exception among studies that many claim to do so.
Reference
H Birlouez-Aragon, I., Saavedra, G., Tessier, F.J., Galinier, A., Ait-Ameur, L., Lacoste, F., Niamba, C.-N., Alt, N., Somoza, V., & Lecerf, J.-M. (2010). A diet based on high-heat-treated foods promotes risk factors for diabetes mellitus and cardiovascular diseases. The American Journal of Clinical Nutrition, 91(5), 1220-1226.
Monday, November 8, 2010
Sunday, November 7, 2010
Why do we make bad decisions? It's evolution, stupid.
In the afternoon session of New Horizons in Science at Yale, psychology professor Laurie Santos delivered a compelling talk on the origins of human irrationality.
Santos studies comparative cognition in primates including humans, chimps, various monkeys, and (my favorite animal) lemurs! There isn't too much about rationality that we don't share with the rest of the primate family.
What makes humans different in irrationality? Well, actually, a lot of us are indeed similarly stupid to most monkeys -- cognitively speaking, because of biases, heuristics, errors in judgment.
It's amazing that we can even become adult humans at all, says Santos. Her research delves into what causes us to be irrational, our "cognitive dissonance."
Cognitive dissonance, it turns out, is shaped by decisions and preferences that lead to our decision making. And, she presented examples of experiments of how they found in adults and children that preferences change dependent on prior decision making.
For example, when children are forced to choose between two stickers (one showing a fish, another animal), they later express avoidance for choices they previously chose against when no additional information is given (Psychological Science, 2007).
Then, the same experiment was performed on monkeys (with M&Ms, not stickers) and found the same -- they prefer to avoid the one they avoided befofe -- when no new information was presented.
She also went through other experiments, in which it was found that we and monkeys consistently make irrational decisions.
A real-world example of irrationality? Our economic choices are often irrational. If we get a $20 parking ticket our emotional responses are often greater than the opposite response produced if we happened to find a $20 bill on the street.
Santos then brought in some audience participation giving us simple choices in which we'd have to make some kind of risk analysis. If we have a coffee mug for sale, we often have a higher perceived value of it versus if we were buying it.
Basically, the feeling you get from potential loss aversion is often stronger than the feeling you get from potential gain.
In a primate trading method experiment, Santos describes how her team gave monkeys tokens to buy "products" and she shows a video of the monkeys making choices depending on the products given.
Do monkeys have a concept of ownership? She showed that the "endowment effect" does exist in monkeys. If given cereal or fruit (which they treat with equal preference) to trade for the opposite, they will prefer what they were originally given. However, if the monkeys are given the choice of trading their goods for a "good deal" like fruit roll-ups, then they'll capitalize the opportunity.
The capuchins evaluate choices relative to reference points, they exhibit loss aversion, endowment effect, and switch preferences depending on how risk is presented (avoiding loss aversion).
"What we're starting to discover..." Santos says, "a lot of these irrationalities are shared broadly across the primate order suggesting that they originated in a common ancestor."
So, what are the next steps? "We like to think of our species as special," so if we find the kinds of things that show a unique bias, then we can understand more about what makes humans unique.
Also, how does advertising work? They're designing experiments where they show advertisements to the monkeys like an alpha male drinking Coke versus Pepsi, with the thought suggested, "Be alpha male, drink Coke!"
In short, Santos proposes, we can learn a lot about ourselves by researching not just how smart we are, but how "dumb we are" too. After all, we are apt to purposely lose with intent of punishing others, an example of emotional human irrationality.
There may even be cases of uniquely human irrationalities.
Santos studies comparative cognition in primates including humans, chimps, various monkeys, and (my favorite animal) lemurs! There isn't too much about rationality that we don't share with the rest of the primate family.
What makes humans different in irrationality? Well, actually, a lot of us are indeed similarly stupid to most monkeys -- cognitively speaking, because of biases, heuristics, errors in judgment.
It's amazing that we can even become adult humans at all, says Santos. Her research delves into what causes us to be irrational, our "cognitive dissonance."
Cognitive dissonance, it turns out, is shaped by decisions and preferences that lead to our decision making. And, she presented examples of experiments of how they found in adults and children that preferences change dependent on prior decision making.
For example, when children are forced to choose between two stickers (one showing a fish, another animal), they later express avoidance for choices they previously chose against when no additional information is given (Psychological Science, 2007).
Then, the same experiment was performed on monkeys (with M&Ms, not stickers) and found the same -- they prefer to avoid the one they avoided befofe -- when no new information was presented.
She also went through other experiments, in which it was found that we and monkeys consistently make irrational decisions.
A real-world example of irrationality? Our economic choices are often irrational. If we get a $20 parking ticket our emotional responses are often greater than the opposite response produced if we happened to find a $20 bill on the street.
Santos then brought in some audience participation giving us simple choices in which we'd have to make some kind of risk analysis. If we have a coffee mug for sale, we often have a higher perceived value of it versus if we were buying it.
Basically, the feeling you get from potential loss aversion is often stronger than the feeling you get from potential gain.
In a primate trading method experiment, Santos describes how her team gave monkeys tokens to buy "products" and she shows a video of the monkeys making choices depending on the products given.
Do monkeys have a concept of ownership? She showed that the "endowment effect" does exist in monkeys. If given cereal or fruit (which they treat with equal preference) to trade for the opposite, they will prefer what they were originally given. However, if the monkeys are given the choice of trading their goods for a "good deal" like fruit roll-ups, then they'll capitalize the opportunity.
The capuchins evaluate choices relative to reference points, they exhibit loss aversion, endowment effect, and switch preferences depending on how risk is presented (avoiding loss aversion).
"What we're starting to discover..." Santos says, "a lot of these irrationalities are shared broadly across the primate order suggesting that they originated in a common ancestor."
So, what are the next steps? "We like to think of our species as special," so if we find the kinds of things that show a unique bias, then we can understand more about what makes humans unique.
Also, how does advertising work? They're designing experiments where they show advertisements to the monkeys like an alpha male drinking Coke versus Pepsi, with the thought suggested, "Be alpha male, drink Coke!"
In short, Santos proposes, we can learn a lot about ourselves by researching not just how smart we are, but how "dumb we are" too. After all, we are apt to purposely lose with intent of punishing others, an example of emotional human irrationality.
There may even be cases of uniquely human irrationalities.
Location:Chapel St,New Haven,United States
What microbes in our soil (not dirt!) mean to us
Most people have no idea just how large the role of microbes play as a part in our world, in our soil, in our bodies. That was the introduction we received on the subject from Yale professor Jo Handelsman at New Horizons in Science (as part of #sciwri10).
As a molecular, cellular and developmental biologist, Handelsman takes issue with any scientist or science writer who dares refer to the world's largest organ as simply "dirt" (a mistake I've already made and won't make again).
In human health, microbes do a lot more than we thought, says Handelsman. There are interesting associations of feelings like anger and different composition of human gut microbiota. Microbes or microbial products or microbial interactions with host tissues are also shown in animals to be linked to diseases including obesity, diabetes, etc. (apart from genetics and diet).
We are "microbial organisms"! says Handelsman, noting that our bodies contain 10 times more microbes than cells. Similarly, the Earth is largely a microbial organism as the microbes affect climate, provide most of the nitrogen on the planet, and make up the soil that produces our food.
How much do microbes play in climate? A lot. The microbes in the ocean are what fix much of the carbon creating oxygen, but "the plants get most of the credit."
Bacteria are also what stabilizes the soil, by living and forming the crust on the surface of sand -- preventing erosion and providing planetary health.
So, in reality, microbes are good! They are not simply pathogens and toxic, as many people believe, says Handelsman.
Soil itself is mostly microbial with 10 billion bacteria per gram. Soil supports 95 percent of our food. And soil bacteria are our primary source for antibiotic drugs.
Antibiotics, in particular, present a reason why we must study soil. There are few antibiotics in the pharmaceutical industry pipeline, there's bacterial resistance to most antibiotics in use, and overuse and abuse is worsening the problem.
"Now we're facing a health crisis that is unprecedented," says Handelsman. "But worse than that is that industry has abandoned the study of antibiotics (with the exception of Merck and Pfizer)."
This is scary considering the growth and density of the human population, which could lead to a major catastrophe that Handelsman says "we are not prepared for."
She then shows a graph to illustrate an example of how resistant bacterial strains can spread rapidly, which cannot be treated -- an area of "enormous concern" of which she studies.
Why does antibiotic resistance exist? It's well established that excessive use, especially in livestock, creates the development of resistance. The antibiiotics used on animals leaks into the environment, into the soil, into the water.
About a decade ago, Handelsman and her team developed microbial observatories to study the soil. They asked questions about whether or not antibiotic resistance genes move from soil to humans, where are the origins, and is there contact between soil and wounds (such as in Iraq, Afghanistan).
Her team has three sites for microbial observation: West Madison, Alaska, and Epplegarden. The sites are strategically located to collect data on how antibiotics overuse could lead to antibiotic resistance.
Coming back now to soil bacteria, she notes that most bacteria that we know of can't be cultured. They are dramatically different than bacteria we can culture. So, how to identify and study?
The team developed "metagenomics" ("bypassing the culturing step") and going to genomic analysis. They also analyze the activities expressed by clones carrying fragments of genomic DNA extracted from the organism assemblage.
In other words, they take a sample of soil, place it in a vessel, extract DNA, clean uop the DNA (because it's "dirty"!), and then replicate by introducing DNA fragments into E. coli.
For example, they take E. coli resistant to kanamycin (an aminoglycoside), penicillin resistance, then isolate genes that are responsible for the resistance. They found three kanamycin-resistant genes in orchard soil, which produced fusions of proteins that conferred the resistance.
Handelsman also described what they found when they looked at Alaskan soil bacteria with beta-lactam (amoxicillin, penicillin) resistance. The bacteria harbored a gene producing bifunctional enzyme, beta-lactamase.
"Interestingly, the resistance genes were relatively poorly related to other known resistance genes," Handelsman says. So, the data reveal that bacteria don't have specific "drug-resistant determinant."
Antibiotic use in livestock, agriculture, "pig operations, in particular," is an environment ripe for drug-resistant strains of microbes. An example is flurophenicol.
In apple orchards, sprayed with streptomycin, there was concern about strep resistance. But they found that there was little resistance since, perhaps, the strep didn't penetrate the soil. Also, the strep-resistance genes in humans were not the same.
Takeaways? Bacteria are wonderful, should be revered. Most aren't culturable, metagenomics provides us access to unculturable bacteria. Through metagenomics we've also discovered novel resistant genes, raising question about resistance origins, such as agricultural practices that raise more questions. In short, soil is super and needs more study.
In the Q&A session, Handelsman also commented on the unwillingness of the meat industry to understand, or do anything about, the evidence showing the problems with antibiotic resistance related to agricultural practices. Their defense, "the data are inconclusive."
If you found the idea of metagenomics as neat as I did, then you might also find Jo Handelsman's 2004 paper on the subject interesting, which is published in Microbiology and Molecular Biology Reviews.
As a molecular, cellular and developmental biologist, Handelsman takes issue with any scientist or science writer who dares refer to the world's largest organ as simply "dirt" (a mistake I've already made and won't make again).
In human health, microbes do a lot more than we thought, says Handelsman. There are interesting associations of feelings like anger and different composition of human gut microbiota. Microbes or microbial products or microbial interactions with host tissues are also shown in animals to be linked to diseases including obesity, diabetes, etc. (apart from genetics and diet).
We are "microbial organisms"! says Handelsman, noting that our bodies contain 10 times more microbes than cells. Similarly, the Earth is largely a microbial organism as the microbes affect climate, provide most of the nitrogen on the planet, and make up the soil that produces our food.
How much do microbes play in climate? A lot. The microbes in the ocean are what fix much of the carbon creating oxygen, but "the plants get most of the credit."
Bacteria are also what stabilizes the soil, by living and forming the crust on the surface of sand -- preventing erosion and providing planetary health.
So, in reality, microbes are good! They are not simply pathogens and toxic, as many people believe, says Handelsman.
Soil itself is mostly microbial with 10 billion bacteria per gram. Soil supports 95 percent of our food. And soil bacteria are our primary source for antibiotic drugs.
Antibiotics, in particular, present a reason why we must study soil. There are few antibiotics in the pharmaceutical industry pipeline, there's bacterial resistance to most antibiotics in use, and overuse and abuse is worsening the problem.
"Now we're facing a health crisis that is unprecedented," says Handelsman. "But worse than that is that industry has abandoned the study of antibiotics (with the exception of Merck and Pfizer)."
This is scary considering the growth and density of the human population, which could lead to a major catastrophe that Handelsman says "we are not prepared for."
She then shows a graph to illustrate an example of how resistant bacterial strains can spread rapidly, which cannot be treated -- an area of "enormous concern" of which she studies.
Why does antibiotic resistance exist? It's well established that excessive use, especially in livestock, creates the development of resistance. The antibiiotics used on animals leaks into the environment, into the soil, into the water.
About a decade ago, Handelsman and her team developed microbial observatories to study the soil. They asked questions about whether or not antibiotic resistance genes move from soil to humans, where are the origins, and is there contact between soil and wounds (such as in Iraq, Afghanistan).
Her team has three sites for microbial observation: West Madison, Alaska, and Epplegarden. The sites are strategically located to collect data on how antibiotics overuse could lead to antibiotic resistance.
Coming back now to soil bacteria, she notes that most bacteria that we know of can't be cultured. They are dramatically different than bacteria we can culture. So, how to identify and study?
The team developed "metagenomics" ("bypassing the culturing step") and going to genomic analysis. They also analyze the activities expressed by clones carrying fragments of genomic DNA extracted from the organism assemblage.
In other words, they take a sample of soil, place it in a vessel, extract DNA, clean uop the DNA (because it's "dirty"!), and then replicate by introducing DNA fragments into E. coli.
For example, they take E. coli resistant to kanamycin (an aminoglycoside), penicillin resistance, then isolate genes that are responsible for the resistance. They found three kanamycin-resistant genes in orchard soil, which produced fusions of proteins that conferred the resistance.
Handelsman also described what they found when they looked at Alaskan soil bacteria with beta-lactam (amoxicillin, penicillin) resistance. The bacteria harbored a gene producing bifunctional enzyme, beta-lactamase.
"Interestingly, the resistance genes were relatively poorly related to other known resistance genes," Handelsman says. So, the data reveal that bacteria don't have specific "drug-resistant determinant."
Antibiotic use in livestock, agriculture, "pig operations, in particular," is an environment ripe for drug-resistant strains of microbes. An example is flurophenicol.
In apple orchards, sprayed with streptomycin, there was concern about strep resistance. But they found that there was little resistance since, perhaps, the strep didn't penetrate the soil. Also, the strep-resistance genes in humans were not the same.
Takeaways? Bacteria are wonderful, should be revered. Most aren't culturable, metagenomics provides us access to unculturable bacteria. Through metagenomics we've also discovered novel resistant genes, raising question about resistance origins, such as agricultural practices that raise more questions. In short, soil is super and needs more study.
In the Q&A session, Handelsman also commented on the unwillingness of the meat industry to understand, or do anything about, the evidence showing the problems with antibiotic resistance related to agricultural practices. Their defense, "the data are inconclusive."
If you found the idea of metagenomics as neat as I did, then you might also find Jo Handelsman's 2004 paper on the subject interesting, which is published in Microbiology and Molecular Biology Reviews.
Location:Chapel St,New Haven,United States
On the Hunt for Neuropsychiatric Disorder Genes
Next speaker up at New Horizons in Science is co-director of Yale's Neurogenetics Program Matthew State, a child psychiatrist who describes himself as a gene hunter.
The genes he seeks out are those that may be linked to child neuropsychiatric disorders including autism, Tourette, and obsessive-compulsive disorders.
What he and other researchers use as a tool is high-throughput, high-resolution genomic analysis, which is so fast that in the near future we may know quite a bit more about many of the chromosomal rearrangements linked to several genetics disorders.
However, he says, "we still have not been able to find a single common variation" in gene sequence that explains any of the child psychiatric disorders. But, he expresses a certain excitement about the future of genomics analysis because of fast technologies.
What he predicts is that rare gene variations, or rare combinations of gene variations, will finally explain the etiology of the child psychiatric disorders. Soon, we'll know enough to put the science on par with other more-understood diseases like cancer.
He shares findings from his lab, published in Nature last month, of a defective gene involved in the expression of histamine, which is linked to neuropsychiatric disorders.
Histamine acts as a neuromodulator that opposes dopamine activity, so the discovery may lead to a number of compounds already in clinical trials related to histamine as options for potential treatments.
Dr. State also shared information about the pathways that are involved or may be involved in autistic spectrum disorders.
The point, really, that he's pushing in this talk is that "next-generation sequencing helps us map pedigrees that we couldn't map before." In fact, he adds, "new sequencing technology is transforming" the entire way we look at the future of medicine.
Many genes lead to a phenotype and one gene that goes wrong can lead to large implications in a phenotype. The complexity of genetic disorders, unfortunately, is staggering.
So far the study of genetics has not produced much in terms of real-world treatments and benefits because of complexity, Dr. State says. He has high hopes for what cheaper, faster methods will bring in the future.
The genes he seeks out are those that may be linked to child neuropsychiatric disorders including autism, Tourette, and obsessive-compulsive disorders.
What he and other researchers use as a tool is high-throughput, high-resolution genomic analysis, which is so fast that in the near future we may know quite a bit more about many of the chromosomal rearrangements linked to several genetics disorders.
However, he says, "we still have not been able to find a single common variation" in gene sequence that explains any of the child psychiatric disorders. But, he expresses a certain excitement about the future of genomics analysis because of fast technologies.
What he predicts is that rare gene variations, or rare combinations of gene variations, will finally explain the etiology of the child psychiatric disorders. Soon, we'll know enough to put the science on par with other more-understood diseases like cancer.
He shares findings from his lab, published in Nature last month, of a defective gene involved in the expression of histamine, which is linked to neuropsychiatric disorders.
Histamine acts as a neuromodulator that opposes dopamine activity, so the discovery may lead to a number of compounds already in clinical trials related to histamine as options for potential treatments.
Dr. State also shared information about the pathways that are involved or may be involved in autistic spectrum disorders.
The point, really, that he's pushing in this talk is that "next-generation sequencing helps us map pedigrees that we couldn't map before." In fact, he adds, "new sequencing technology is transforming" the entire way we look at the future of medicine.
Many genes lead to a phenotype and one gene that goes wrong can lead to large implications in a phenotype. The complexity of genetic disorders, unfortunately, is staggering.
So far the study of genetics has not produced much in terms of real-world treatments and benefits because of complexity, Dr. State says. He has high hopes for what cheaper, faster methods will bring in the future.
Location:Church St,New Haven,United States
Deep-brain stimulation for depression
On Sunday morning at New Horizons in Science at Yale -- after some coffee for brain stimulation -- we were treated to our first science talk of the day: on deep-brain stimulation as a treatment for severe depression.
Emory University professor of psychiatry and neurology Helen Mayberg, MD, showed us several brain scans she uses to study moods and neural networks. She can tell from these neural images whether you're glad, mad or sad.
Then, she targets areas of the brain with what she describes as an "implantation of a very, small wire... with electrodes on the end." The electrodes are guided to wherever she wants it in the brain and an IPG is implanted in the chest.
Dr. Mayberg worried about the safety of acute stimulation of areas of the brain. What happens if you stimulate the hypothalamus and it causes a drop in blood pressure? But she couldn't rely on surgeons as "gatekeepers," so she performed intra-operative safety testing.
During the testing, patients self-reported spontaneous feelings such as "intense calm" or resolution of pain and dread -- interoceptive release. These reports happened patient after patient, says Dr. Mayberg, so she knew something was going on. The feelings were followed by interest, energy -- exteroceptive awareness.
Dr. Mayberg's first study was published in 2005, then she expanded and published again in 2008 (in Biol Psych). The studies showed deep-brain stimulation was effective in treatment-resistant depression. "The [patients] not only got better, they stayed better," she says.
She then gave us some preliminary results of an Emory study of active treatment for six months with a two-year follow-up on bipolar and unipolar patients. The results so far look very, very promising. "This is an anti-depressant treatment, not a mood stabilizer," says Dr. Mayberg. "No one remains in pre-treatment state, everyone is on road to recovery."
She says now we know not just where to stimulate in the brain, but what fibers must be impacted for the treatment -- a treatment that can take patients with "gnawing pain" or feelings of "being in a room with 10 screaming children" to a place of a finding serious relief.
So, what's next? Dr. Mayberg says the treatment needs to go through a series of placebo-controlled trials to establish safety and to confirm initial results.
Even more exciting, however, is that with neural images it may be possible to soon predict and even prevent depression. "This is teaching us an amazing amount about depression," Dr. Mayberg says. The more we learn, the greater the understanding of what goes wrong in neural networks that leads to development of severe depressive disorders.
She's careful to point out that a stimulator is not the only thing you need to come out of a depressive state and it's not a device that will ever guarantee that people can forever say goodbye to "bad days."
But along with continual therapy over time, from a patient's perspective, the treatment can mean the difference between feeling like you are at the bottom of the Grand Canyon without any chance of hiking out and the feeling that you have when you have a pathway toward the top.
Emory University professor of psychiatry and neurology Helen Mayberg, MD, showed us several brain scans she uses to study moods and neural networks. She can tell from these neural images whether you're glad, mad or sad.
Then, she targets areas of the brain with what she describes as an "implantation of a very, small wire... with electrodes on the end." The electrodes are guided to wherever she wants it in the brain and an IPG is implanted in the chest.
Dr. Mayberg worried about the safety of acute stimulation of areas of the brain. What happens if you stimulate the hypothalamus and it causes a drop in blood pressure? But she couldn't rely on surgeons as "gatekeepers," so she performed intra-operative safety testing.
During the testing, patients self-reported spontaneous feelings such as "intense calm" or resolution of pain and dread -- interoceptive release. These reports happened patient after patient, says Dr. Mayberg, so she knew something was going on. The feelings were followed by interest, energy -- exteroceptive awareness.
Dr. Mayberg's first study was published in 2005, then she expanded and published again in 2008 (in Biol Psych). The studies showed deep-brain stimulation was effective in treatment-resistant depression. "The [patients] not only got better, they stayed better," she says.
She then gave us some preliminary results of an Emory study of active treatment for six months with a two-year follow-up on bipolar and unipolar patients. The results so far look very, very promising. "This is an anti-depressant treatment, not a mood stabilizer," says Dr. Mayberg. "No one remains in pre-treatment state, everyone is on road to recovery."
She says now we know not just where to stimulate in the brain, but what fibers must be impacted for the treatment -- a treatment that can take patients with "gnawing pain" or feelings of "being in a room with 10 screaming children" to a place of a finding serious relief.
So, what's next? Dr. Mayberg says the treatment needs to go through a series of placebo-controlled trials to establish safety and to confirm initial results.
Even more exciting, however, is that with neural images it may be possible to soon predict and even prevent depression. "This is teaching us an amazing amount about depression," Dr. Mayberg says. The more we learn, the greater the understanding of what goes wrong in neural networks that leads to development of severe depressive disorders.
She's careful to point out that a stimulator is not the only thing you need to come out of a depressive state and it's not a device that will ever guarantee that people can forever say goodbye to "bad days."
But along with continual therapy over time, from a patient's perspective, the treatment can mean the difference between feeling like you are at the bottom of the Grand Canyon without any chance of hiking out and the feeling that you have when you have a pathway toward the top.
Wednesday, November 3, 2010
News and Events
A M A N I F E S T O f o r A R T S
a n d H E A L T H
Thanks to everyone who took part in Fridays first event. A dedicated BLOG is being prepared...
P L A C E B O S f o r A R T
The Behring Institute is seeking placebos for art. With these placebos, long-term research on the influence of art on public health will be carried out. Artists, art lovers, professionals as well as amateurs, are being called on to submit proposals for potential art placebos before 1 January 2011.
Relationships between art and healthcare, as well as the influence and effects of art on health, have been studied frequently. The results of many studies indicate a positive outcome with regard to the health of people and suggest that art can lead to the improvement of mental and physical health. For the purpose of a long-term European study on the effects of art on the health of individuals, the Behring Institute now seeks placebos for art, which can be offered to a control group.
Examples and leads can be e-mailed to Mrs. Andersom, j.andersom@behringinstitute.com, or posted to: Behring Institute, attn: Mw. J. Andersom, Herenmarkt 93F, 1013 EC Amsterdam, The Netherlands. Once the selection process has been completed, the submitted documentation can unfortunately not be returned.
For more information, see: www.behringinstitute.com Mrs. Andersom of the Behring Institute can be contacted during office hours at j.andersom@behringinstitute.com
New website
Health professionals can find out how creative activities can benefit people affected by long-term conditions, and locate local voluntary arts/creative groups, on a new website: www.healthysocialcreative.org.uk The site has been created by Voluntary Arts, to raise awareness of the wealth of creative activities that exist in local communities – from choirs to quilt-makers, dance groups to painting societies, drama groups to samba bands – and the health benefits of taking part.
K E E P L E A R N I N G
S E M I N A R S
19 November–11 December
Building on the positive momentum from 2008, the arts and cultural sector have played a significant role in Liverpool’s Year of Health & Wellbeing. We know that arts and culture impact on our sense of self individually and collectively, and it is increasingly important that we find ways to articulate why this is the case. We are promoting these events as a series to NHS staff, researchers, clinicians and GP’s to raise awareness of the scope, quality and value of this work in the City, and with the hope of engaging more health professionals and researchers in the work going forward, both to raise awareness of Liverpool’s innovation in this area of work and to develop collaborations longer-term as we embark on a Decade of Health and Wellbeing.
Monday, November 1, 2010
Amino acids in skeletal muscle: Are protein supplements as good as advertised?
When protein-rich foods, like meat, are ingested they are first broken down into peptides through digestion. As digestion continues, peptides are broken down into amino acids, which then enter circulation, becoming part of the blood plasma. They are then either incorporated into various tissues, such as skeletal muscle, or used for other purposes (e.g., oxidation and glucose generation). The table below shows the amino acid composition of blood plasma and skeletal muscle. It was taken from Brooks et al. (2005), and published originally in a classic 1974 article by Bergström and colleagues. Essential amino acids, shown at the bottom of the table, are those that have to be consumed through the diet. The human body cannot synthesize them. (Tyrosine is essential in children; in adults tryptophan is essential.)
The data is from 18 young and healthy individuals (16 males and 2 females) after an overnight fast. The gradient is a measure that contrasts the concentration of an amino acid in muscle against its concentration in blood plasma. Amino acids are transported into muscle cells by amino acid transporters, such as the vesicular glutamate transporter 1 (VGLUT1). Transporters exist because without them a substance’s gradient higher or lower than 1 would induce diffusion through cell membranes; that is, without transporters anything would enter or leave cells.
Research suggests that muscle uptake of amino acids is positively correlated with the concentration of the amino acids in plasma (as well as the level of activity of transporters) and that this effect is negatively moderated by the gradient. This is especially true after strength training, when protein synthesis is greatly enhanced. In other words, if the plasma concentration of an amino acid such as alanine is high, muscle uptake will be increased (with the proper stimulus; e.g., strength training). But if a lot of alanine is already present in muscle cells when compared to plasma (which is normally the case, since alanine’s 7.3 gradient is relatively high), more plasma alanine will be needed to increase muscle uptake.
The amino acid makeup of skeletal muscle is a product of evolutionary forces, which largely operated on our Paleolithic ancestors. Those ancestors obtained their protein primarily from meat, eggs, vegetables, fruits, and nuts. Vegetables and fruits today are generally poor sources of protein; that was probably the case in the Paleolithic as well. Also, only when very young our Paleolithic ancestors obtained their protein from human milk. It is very unlikely that they drank the milk of other animals. Still, many people today possess genetic adaptations that enable them to consume milk (and dairy products in general) effectively due to a more recent (Neolithic) ancestral heritage. A food-related trait can evolve very fast – e.g., in a few hundred years.
One implication of all of this is that protein supplements in general may not be better sources of amino acids than natural protein-rich foods, such as meat or eggs. Supplements may provide more of certain amino acids than others sources, but given the amino acid makeup of skeletal muscle, a supplemental overload of a particular amino acid is unlikely to be particularly healthy. That overload may induce an unnatural increase in amino acid oxidation, or an abnormal generation of glucose through gluconeogenesis. Depending on one’s overall diet, those may in turn lead to elevated blood glucose levels and/or a caloric surplus. The final outcome may be body fat gain.
Another implication is that man-made foods that claim to be high in protein, and that are thus advertised as muscle growth supplements, may actually be poor sources of those amino acids whose concentration in muscle are highest. (You need to check the label for the amino acid composition, and trust the manufacturer.) Moreover, if they are sources of nonessential amino acids, they may overload your body if you consume a balanced diet. Interestingly, nonessential amino acids are synthesized from carbon sources. A good source of carbon is glucose.
Among the essential amino acids are a group called branched-chain amino acids (BCAA) – leucine, isoleucine, and valine. Much is made of these amino acids, but their concentration in muscle in adults is not that high. That is, they do not contribute significantly as building blocks to protein synthesis in skeletal muscle. What makes BCAAs somewhat unique is that they are highly ketogenic, and somewhat glucogenic (via gluconeogenesis). They also lead to insulin spikes. Ingestion of BCAAs increases the blood concentration of two of the three human ketone bodies (acetone and acetoacetate). Ketosis is both protein and glycogen sparing (but gluconeogenesis is not), which is among the reasons why ketosis is significantly induced by exercise (blood ketones concentration is much more elevated after exercise than after a 20 h fast). This is probably why some exercise physiologists and personal trainers recommend consumption of BCAAs immediately prior to or during anaerobic exercise.
Why do carnivores often consume prey animals whole? (Consumption of eggs is not the same, but similar, because an egg is the starting point for the development of a whole animal.) Carnivores consume prey animals whole arguably because prey animals have those tissues (muscle, organ etc. tissues) that carnivores also have, in roughly the same amounts. Prey animals that are herbivores do all the work of converting their own prey (plants) to tissues that they share with carnivores. Carnivores benefit from that work, paying back herbivores by placing selective pressures on them that are health-promoting at the population level. (Carnivores usually target those prey animals that show signs of weakness or disease.)
Supplements would be truly natural if they provided nutrients that mimicked eating an animal whole. Most supplements do not get even close to doing that; and this includes protein supplements.
Reference
Brooks, G.A., Fahey, T.D., & Baldwin, K.M. (2005). Exercise physiology: Human bioenergetics and its applications. Boston, MA: McGraw-Hill.
The data is from 18 young and healthy individuals (16 males and 2 females) after an overnight fast. The gradient is a measure that contrasts the concentration of an amino acid in muscle against its concentration in blood plasma. Amino acids are transported into muscle cells by amino acid transporters, such as the vesicular glutamate transporter 1 (VGLUT1). Transporters exist because without them a substance’s gradient higher or lower than 1 would induce diffusion through cell membranes; that is, without transporters anything would enter or leave cells.
Research suggests that muscle uptake of amino acids is positively correlated with the concentration of the amino acids in plasma (as well as the level of activity of transporters) and that this effect is negatively moderated by the gradient. This is especially true after strength training, when protein synthesis is greatly enhanced. In other words, if the plasma concentration of an amino acid such as alanine is high, muscle uptake will be increased (with the proper stimulus; e.g., strength training). But if a lot of alanine is already present in muscle cells when compared to plasma (which is normally the case, since alanine’s 7.3 gradient is relatively high), more plasma alanine will be needed to increase muscle uptake.
The amino acid makeup of skeletal muscle is a product of evolutionary forces, which largely operated on our Paleolithic ancestors. Those ancestors obtained their protein primarily from meat, eggs, vegetables, fruits, and nuts. Vegetables and fruits today are generally poor sources of protein; that was probably the case in the Paleolithic as well. Also, only when very young our Paleolithic ancestors obtained their protein from human milk. It is very unlikely that they drank the milk of other animals. Still, many people today possess genetic adaptations that enable them to consume milk (and dairy products in general) effectively due to a more recent (Neolithic) ancestral heritage. A food-related trait can evolve very fast – e.g., in a few hundred years.
One implication of all of this is that protein supplements in general may not be better sources of amino acids than natural protein-rich foods, such as meat or eggs. Supplements may provide more of certain amino acids than others sources, but given the amino acid makeup of skeletal muscle, a supplemental overload of a particular amino acid is unlikely to be particularly healthy. That overload may induce an unnatural increase in amino acid oxidation, or an abnormal generation of glucose through gluconeogenesis. Depending on one’s overall diet, those may in turn lead to elevated blood glucose levels and/or a caloric surplus. The final outcome may be body fat gain.
Another implication is that man-made foods that claim to be high in protein, and that are thus advertised as muscle growth supplements, may actually be poor sources of those amino acids whose concentration in muscle are highest. (You need to check the label for the amino acid composition, and trust the manufacturer.) Moreover, if they are sources of nonessential amino acids, they may overload your body if you consume a balanced diet. Interestingly, nonessential amino acids are synthesized from carbon sources. A good source of carbon is glucose.
Among the essential amino acids are a group called branched-chain amino acids (BCAA) – leucine, isoleucine, and valine. Much is made of these amino acids, but their concentration in muscle in adults is not that high. That is, they do not contribute significantly as building blocks to protein synthesis in skeletal muscle. What makes BCAAs somewhat unique is that they are highly ketogenic, and somewhat glucogenic (via gluconeogenesis). They also lead to insulin spikes. Ingestion of BCAAs increases the blood concentration of two of the three human ketone bodies (acetone and acetoacetate). Ketosis is both protein and glycogen sparing (but gluconeogenesis is not), which is among the reasons why ketosis is significantly induced by exercise (blood ketones concentration is much more elevated after exercise than after a 20 h fast). This is probably why some exercise physiologists and personal trainers recommend consumption of BCAAs immediately prior to or during anaerobic exercise.
Why do carnivores often consume prey animals whole? (Consumption of eggs is not the same, but similar, because an egg is the starting point for the development of a whole animal.) Carnivores consume prey animals whole arguably because prey animals have those tissues (muscle, organ etc. tissues) that carnivores also have, in roughly the same amounts. Prey animals that are herbivores do all the work of converting their own prey (plants) to tissues that they share with carnivores. Carnivores benefit from that work, paying back herbivores by placing selective pressures on them that are health-promoting at the population level. (Carnivores usually target those prey animals that show signs of weakness or disease.)
Supplements would be truly natural if they provided nutrients that mimicked eating an animal whole. Most supplements do not get even close to doing that; and this includes protein supplements.
Reference
Brooks, G.A., Fahey, T.D., & Baldwin, K.M. (2005). Exercise physiology: Human bioenergetics and its applications. Boston, MA: McGraw-Hill.
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