Wednesday, October 29, 2008
/type one/9 .
They explain it like this; 'We hypothesized that this effect was due to the interaction of a "catalytic" dose of fructose with the regulatory protein for glucokinase in glucose-sensing cells that drive counterregulation. '
When a sugar molecule is phosphorylated, it makes it harder for that sugar to leave the cell. Fructose that is absorbed and then finds it's way to the liver, for example, is phosphorylated by fructokinase, and sort of stays put to be converted into glucose or fat or glycerine.
From the discussion;
"In concert with the augmentation of epinephrine release during hypoglycemia, the fructose studies were accompanied by significantly higher rates of EGP during the 3.9- and 3.3-mmol/l glucose steps and corresponding decreases in glucose infusion rates. Moreover, because of this enhanced counterregulatory response in the fructose studies, we were unable to lower the plasma glucose levels below 3.9 mmol/l."
Monday, October 27, 2008
This guy here http://www.sns-web.org/pages/advances/01/article.asp is doing work investigating the idea that rather than being just a symptom of insulin resistance and metabolic syndrome in general, high blood pressure might also be a cause of insulin resistance, making it harder to get nutrients and insulin to muscle and other cells.
Dr William Davis writes about wheat belly, suggesting that cutting wheat out of the diet will help to reduce central obesity--or visceral fat.
Removing visceral fat from rats and then feeding them a diet that would normally induce type 2 diabetes fails to do so. They've done the same to a lesser degree with humans. I don't think they can remove the whole organ from a human being; it probably has legitimate functions in the body.
This study http://hyper.ahajournals.org/cgi/content/abstract/27/1/125 looks at a possible connection between loss of visceral fat and lowered blood pressure. If you read a lot of low carb books and spend some time on some blogs and forums, you'll see that a decreased waist circumference is claimed very often, as well as decreased blood pressure.
My sister sent me an article at work today. Hydrogen Sulfide, a chemical produced by some gut bacteria and present in farts, lowers blood pressure. An enzyme the article called "CSE" was needed for production of the hydrogen sulfide.
Devil of a time finding out what the heck CSE was. Seems like every researcher has their own name for it. I'm pretty sure Cystathionine gamma-lyase is our baby though. (mostly because I found an article clearly stating that this is so.)
Homocysteine is associated with heart disease. Various b vitamins, b12, folic acid, b6, choline, tend to normalize homocysteine levels. Most of the b vitamins are used by the body in various cycles to transform homocysteine into methionine. B6 is instrumental in a pathway that produces cysteine instead of methionine. It seems Cystathionine gamma-lyase is one of the enzymes necessary for the production of cysteine in this manner.
CSE can also be used in a reverse process that takes cysteine apart.
Check this out; http://www.ionchannels.org/showabstract.php?pmid=15497768&redirect=yes&terms=cystathionine+gamma+lyase+cysteine+hydrogen+sulfide
" The H2S produced from cysteine functions as a neuromodulator and smooth muscle relaxant. In glutamatergic neurons, the production of H2S by cystathionine beta-synthase enhances N-methyl-D-aspartate (NMDA) receptor-mediated currents. In smooth muscle cells, H2S produced by cystathionine gamma-lyase enhances the outward flux of potassium by opening potassium channels, leading to hyperpolarization of membrane potential and smooth muscle relaxation"
So a lack of an enzyme that helps produce cysteine from homocysteine, can also cleave cysteine and produce hydrogen sulfide, which could
dilate blood vessels, relieving high blood pressure and maybe improving insulin sensitivity,
relax other smooth muscle cells, like the ones in your lungs for instance. I read a study a while back where researchers were surprised at the high cysteine levels they found in asthma sufferers. They thought they'd be lower. Glycine levels were found to be lowest in the worst cases of asthma in that study. Dimethylglycine and Trimethylglycine (that second one's betaine) both lower homocysteine. Giving rats too much methionine raises homocysteine levels. Glycine reverses this affect of methionine.
Sunday, October 26, 2008
Seen from a Taubesian cellular starvation angle, something suggests itself. There's could be a very simple difference between these three types of people;
Ectomorphs don't store much energy in their fat cells. Therefore, when in the fasting state, they are forced to metabolize lean tissue for energy. Go to Bodybuilding.com and dig around in the forum and you'll find no shortage of very lean teenage boys claiming to have a very hard time building lean mass, even when eating at very high calorie levels.
Endomorphs tend to store too much energy in fat cells, or perhaps have trouble getting out of the fed glucose-burning state and back into the fasting state. So instead of those fatty acids locked up in their fat cells, they turn to lean tissue for fuel.
Mesomorphs have excellent metabolisms. If they eat lots of food, they have no trouble at all storing away both protein and fat. They also have little trouble accessing that fat, probably switching readily between the fed and fasted state. So their muscles get lots of energy when they eat, and lots of energy when they're asleep. Sparing lean tissue.
Taubes writes about adolescent hogs, who, when fed a low-protein diet, simply eat more of it to support growth, and burn the extra calories off. He also mentions research in the late nineteenth century by Carl von Voit and Max Rubner of something like this happening in humans, with overfeeding failing to cause weight gain. This effect is termed luxusconsumption.
Do a search for more recent studies on luxusconsumption, and you get stuff like this 9
with abstracts starting with lines like this;
"In this paper, we redefine the term luxus consumption to mean food waste and overconsumption leading to storage of body fat, health problems, and excess resource utilization."
So what's changed between the late 19th century and today? The usual line is that the measurements have gotten better. We got fancy metabolic chambers, we can measure oxygen utilization and calculate RQ, (respiratory quotient. By measuring oxygen consumption, researchers can calculate how much of a person's energy use is coming from carbs, fat, protein, etc.) Blah blah blah.
It's nice that we have a fancier yardstick. But late nineteenth century researchers were perfectly capable of calculating and tabulating how much food was being consumed, and the composition of that food, and whether or not the subject consuming that food was gaining fat mass. So I don't think we just measure stuff better now really cuts it.
So the charge against Carl von Voit and Max Rubner becomes one of incompetence or of dishonesty. Always possible; but these are serious charges. Especially for a scientist.
But what if it's not the yardstick that changed? What if it was the nature of the thing being measured?
The thing being measured was the effect of overconsumption of food on human fat stores.
Is there anything that can change the effect of food on an organism?
Peter at Hyperlipid posted this article someone sent him in an email; I'm yoinking it here for my own foul purposes;
Florida Researchers Find Consuming Fructose Can Suppress Leptin Hormone, Lead l
Fat cells put out leptin to signal that they're full to overflowing; it's sort of a signal that they have energy to spare and wish to share it. The signal is "heard" at various places in the body, but of particular importance is the hypothalamus. Triglycerides interfere with leptin's ability to send a signal prompting the hypothalamus to respond by sending it's own messengers to sort of redirect that energy. Fructose supplementation is an excellent way to up triglyceride production. Almost any carbohydrate source will do the same, but fructose really does the job.
In the study fructose interfered with the action of leptin not just while the mice ate fructose, but later on when they switched to what they called a high-fat diet, but was probably a high corn starch and high (or even just medium) fat diet.
How else have we changed?
Much is made of inactivity as a cause of childhood weight gain. Tv, computers, video games. One obvious alternative to any association of these activities to weight gain in children is that these are all indoor activities, which might affect vitamin d levels. And it's been shown that vitamin d affects all kinds of things in the body, one of them being thyroid stimulating hormone, which can affect the thyroid which has a rather obvious connection to the availability of stored fat.
I spent my pre-teen years in the 70s, and was lean. Anyone remember The Kroft Supershow? HR Puff 'n Stuff? Gilligans Island, The Addams Family, Scooby Doo, The Flintstones, The Jetsons, Captain Caveman, Bewitched, The Munsters, Happy Days, Laverne and Shirley, All in the Family, Star Trek, Rocket Robin Hood, Looney Tunes, Trouble with Tracy, Definition (some are Canadian, so you might not.) Uncle Bobby The Friendly Giant Sesame Street, Get Smart, Hogan's Heroes, Maude, I Dream of Jeanie, The Brady Bunch, Batman, I think I got in some old Superman reruns, Ponderosa, Little House on the Prairie, The Electric Company, Romper Room, the list just doesn't end. Which doesn't really back up the idea that TV is keeping kids from getting enough sun, compared to my own youth. But I do remember having a pretty dark tan by the end of every summer.
I mentioned vitamin d's connection to the thyroid. (One of them, at least.) How about other nutrients that affect the thyroid? The most obvious one is iodine. I have no idea what the iodine or the thyroid status of the people in the original luxuskonsumption studies might have been, but it's just one more thing modern researchers might need to know before dismissing the results of those studies out of hand. Table salt is iodized, by law. The salt used in industry when producing corn and potato chips or frozen dinners doesn't necessarily have any iodine supplemented. Much of the US and Canada has iodine-deficient soil. Avoiding egg yolks and whole milk (removing the whey from milk removes much of the iodine) wouldn't help any.
Thyroid disorders do seem to be more common than they probably should be. Treatment of choice seems to very rarely involve iodine supplementation, at least from what I can tell from bopping around on the web. The discussions mostly seem to revolve around supplementation of t3 and t4. It's hard to believe that iodine's never the answer. One problem with supplementing iodine in an actual case of iodine deficiency is that it can sometimes cause goiter.
http://www.ajcn.org/cgi/content/full/86/4/1040 This study, "Vitamin A supplementation in iodine-deficient African children decreases thyrotropin stimulation of the thyroid and reduces the goiter rate."
seems to show that vitamin a protects against goiter in iodine deficient areas, even in the absence of iodine supplementation. In the study, vitamin A supplementation decreased thyroid stimulating hormone levels without reducing t4 levels, and the authors suggest that this might show an effect of vitamin a of improving thyroid hormone sensitivity. (Vitamin D, on the other hand, has the reverse effect, increasing output of tsh from the pituitary gland. Which doesn't mean vitamin d bad--it just means you'd better not be vitamin a deficient, is all. It could just be that Vitamin D helps the metabolism notice a need for thyroid hormone, while vitamin A makes your body use the stuff better, in which case the two vitamins wouldn't be antagonist here at all, but rather complementary.)
I don't know if vitamin a would have this anti-goiter effect in those cases where too much iodine precedes the goiter, but it wouldn't be surprising if something involving the balance of vitamin a and d were involved there.
Okay, I wandered all over the place with this. My point was that there are any number of differences in different groups of subjects separated by nutrient status, time, country, what have you. A failure to measure something in one group of people doesn't prove that it doesn't exist in another.
Saturday, October 25, 2008
Calorie-restricted mice live longer than ad-lib fed mice. One peculiarity of these mice is that while they eat less on a food per mouse basis, they actually eat more on a calorie per gram of mouse basis, at least once they've adapted to the diet. So that by eating less, they're sort of in an increased energy state.
Researchers have increased the lifespans of mice in another way, by manipulating a gene, causing the mice to overexpress an enzyme called phosphoenolypyruvate carboxykinases (PEPCK-C). The mice live sixty percent longer, while eating more. They also have more endurance, and the some of the females have the ability to breed at two and a half years, while fertility usually ends at a year for most mice.
One thing that ties these two types of mice together, besides longevity, is that they both enjoy a high availability of energy on a cellular level. One type is calorie restricted, the other is high calorie, but both enjoy longer lives. But, to repeat myself, on a cellular level both enjoy higher energy utility than the usual mouse.
A third example of increased lifespan for mice is the Snell Dwarf Mouse. The name of this study here http://www.jbc.org/cgi/reprint/282/48/35069 "Low Utilization of Circulating Glucose after Food Withdrawal in Snell Dwarf Mice" in itself kind of suggests a link of one more type of long-lived mouse to energy levels. Burning less glucose in the fasted state? What does this mean? One thing it could mean is that these mice are better at switching fuels. When you eat carbs, your body switches over primarily to burning carbohydrate for energy. This is mediated by insulin and various other hormones. You eat carbs, your pancreas puts out insulin, your liver starts repackaging free fatty acids as triglycerides, and meanwhile your major source of energy is carbohydrate. All fine and dandy; once you've burned or stored all the carbs you've eaten, and your blood sugar's returned to normal, you return to your basal, fasted-state energy source, which is primarily fat.
I'd think the better you were at switching back to burning fat, the more continuous the available supply of burnable energy would be to most of the cells in your body.
Intermittent fasting, eating every other day, has also increased rodent lifespan. In the past I've given more attention to the fasting side of the equation, and it makes sense in the context of this post that if a creature switches between the fed and fasted states poorly, then that creature might actually have more energy in the fasting state if that state is prolonged, that creature spending less time in the, for it, low energy "switchover" state. So the prolonged fasted state might be a higher-energy state. If you look at the fed state as well, if the mouse is eating enough on the feeding day to make up for what it didn't eat on the fasting day, then we have a mouse that might have more energy available to its organs and muscles and body in general on it's feeding days as well. So this mouse would get it coming and going; more energy when it ate, more energy than it might normally have between meals given a shorter fasting period.
If the availability of certain enzymes or nutrients was instrumental in the process of switching over from the fed to the fasting state, actually switching over less often between the glucose dominant and the fat dominant energy use states might spare some of those nutrients and further improve general energy availability. L-carnitine comes to mind. The carnitine shuttle helps to make triglycerides available for the production of energy. Free fatty acids seem to sort of wander around at will, triglycerides need a hall pass. L-carnitine is an important part of that hall pass. During the (carb) fed state, triglycerides go up, free fatty acids go down. If tissues can still take in triglycerides during the fed state, it seems obvious that their supply of nutrients would be more constant, and that the supply to those same tissues might be jerkier, lacking l-carnitine. According to this, http://conditioningresearch.blogspot.com/2008_02_03_archive.html, intermittent fasting and calorie restriction both increase levels of l-carnitine.
According to this study http://if,
I had a quote in here but I lost it and I'm tired. Check out the link.
carnitine improves certain markers that worsen with aging.
Resveratrol has been shown to extend life in mice, but only if they're overweight, or at least eating a diet that would otherwise make a mouse overweight. This CBC article
lists positive effects of resveratrol;
Mice that consumed resveratrol on a daily basis had better bones, with increased thickness, volume, mineral content and density than mice fed a standard high-calorie diet.
At 30 months, mice that had resveratrol daily had fewer cataracts than mice fed the high-calorie diet.
Mice on resveratrol had better balance and co-ordination at 21 and 24 months than untreated mice.
Resveratrol had a similar effect to cutting calories in terms of improving liver and muscle function, and reducing fatty deposits in the body.
Mice fed a high-calorie diet but also given resveratrol lived longer than mice only consuming a high-calorie diet, suggesting the compound may improve longevity copyright cbc 2008
After reading Taubes, the reduced fatty deposits in the body don't suggest lost weight as a cause of the benefits to muscle and liver function and to bone mass and reduced cataracts and improved brain and central nervous system function (or you just could say balance and coordination like they did.) Anymore than body fat was a cause of those ills in the first place. It suggests the possibility that at least some of these ills happen because the muscles, the liver, the bones, etc., aren't getting enough calories to maintain proper function.
The stuff you're made of isn't static; protein in your muscles constantly is broken down and synthesized, bone is broken down and reworked (they use the words resorption and formation), the triglycerides in your fat cells are broken down into free fatty acids and fatty acids are sythesized into triglycerides again. And so on through the body. And these processes of breakdown and synthesis go on simultaneously, and continuously, although one or the other may be dominant at any one moment.
When triglycerides are broken down into free fatty acids, it's easier for the fat to escape the fat cell and be available to the body's other tissues as fuel. When protein is broken down into amino acids, it's easier for the amino acids to escape the (muscle, bone, whatever) cell and be available to the body's other tissues as fuel.
What if, say, a muscle cell is going along, in a high energy state, taking proteins apart, putting them back together, again and again, and suddenly--crash! It lacks an external source of energy. So it ends up feeding on itself; it wastes away. If this happens too often, it may end up unviable.
If the same thing happens with bones, the more rigid nature of bone structure might lead to somewhat porous bones.
Back to the resveratrol, the mice in the study didn't eat more minerals, but they ended up with more minerals in their bones. What changed was not mineral availability, but the body's ability to do the work necessary to put those minerals where they'd do the most good.
Growth hormone increases breakdown of fat. And it increases (or at least protects) muscle mass and bone mass. Men have more muscle than women. Testosterone decreases body fat--but is that what's important here? I'd rather say again, it keeps energy from being locked away, that is, it increases energy availability to bone and muscle tissue.
Weight training has been shown to be effective against both sarcopenia and osteoporosis. The body responds to weight training by releasing certain hormones (growth hormone, testosterone, um and stuff) that encourage the release of fatty acids from the fat cells. More energy=stronger bones, bigger muscles. Longer life?