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Thread: MD Fat Bytes

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    MD Fat Bytes

    By Steve Blechman and Tom Fahey, Ed.D.

    Low Carbohydrate Diets Linked to Long-Term Psychological Problems

    Losing weight is psychological torture for most people. The long-term success of weight loss diets depends on the psychological capacity to eat less food. Australian researchers found that people following low-fat diets (LF; 46 percent carbohydrate, 24 percent protein, and 30 percent fat) were psychologically healthier after 12 months than those following low-carbohydrate diets (LC; 35 percent protein, 61 percent fat, 4 percent carbohydrate). Both groups ate reduced-calorie diets (1,433 calories per day for women and 1,672 calories per day for men) and lost similar amounts of weight (30 pounds).

    At 12 months, the low-carb group scored higher in measures of depression, anxiety, anger-hostility, tension, and dejection. The LF group showed less fatigue and better all-around mood. Reduced-calorie diets that are either low or high in carbohydrates produce similar weight loss after a year, but long-term adherence to a low-carbohydrate diet produces more psychological side effects. (Archives Internal Medicine, 169: 1873-1880, 2009)

    Are Your Genes Keeping You From Getting Into Your Jeans?

    Genes play an important role in regulating bodyweight, appetite, and metabolic rate. It seems as though some people can eat whatever they want and not get fat, while others have trouble losing weight even when they eat normally.

    Delores Corella from Tufts University in Boston and co-researchers found that people with a variant (polymorphism) of the APOA2 gene (CC genotype) showed a disproportionate gain in body mass index (proportion of weight to height) when they ate more saturated fat in their diets. However, they only became obese when they ate excessive amounts of saturated fat. Saturated fat intake was less significant in boosting body mass index in people with other variants of the gene (i.e., TT and TC genotypes).

    The study showed that genes make some people more prone to obesity than others, but that behavioral factors, such as reducing fat intake, could compensate for “fat genes.” (Archives Internal Medicine, 169: 1897-1906, 2009)

    Regular Exercise Causes Weight Loss Without Dieting

    The role of exercise in weight control is controversial. Most studies show that a combination of caloric restriction and exercise are best for weight loss and weight maintenance. However, other studies showed that some people could lose a substantial amount of body fat through exercise alone.

    Buck Willis from Landmark Medical in Austin, Texas and colleagues found that people who exercised at a moderate intensity for 30 minutes, four or more days a week for eight weeks lost 13 pounds of fat in eight weeks. Fat loss was insignificant in those who exercised three days per week or less. The subjects were instructed to consume their normal diet. The exercise program followed the 1996 recommendations of the U.S. Surgeon General and are consistent with the more recent recommendations of the U.S. Department of Health and Human Services. This was only an eight-week study, so the results might not apply to long-term weight control. (Journal Strength and Conditioning Research, 23: 2377-2380, 2009)

    Is Diet or Exercise Best For Weight Loss?

    If present trends continue, 43 percent of Americans will be obese in just eight years. Obesity is contributing to the public health nightmare in the United States. In spite of spending more money per capita on medical care than any other country, we rank 31st in the world in life expectancy and 19th in deaths from preventable conditions such as obesity. Experts have argued vigorously about the causes of the obesity epidemic. Some say that physical inactivity is the culprit, while others claim that increased caloric intake is the cause.

    Critics of the physical inactivity hypothesis claim that the caloric expenditure from exercise is not significant enough to trigger widespread obesity. An editorial by James Hill in the journal Obesity and Weight Management stated that both caloric restriction and exercise are necessary for weight control, and that concentrating on only one factor is dumb. (Obesity Weight Management, 5: 195-196, 2009)

    Liraglutide Reduces Body Fat Better Than Orlistat

    Orlistat is a prescription weight-loss drug approved by the U.S. Food and Drug Administration. It works by decreasing fat absorption during digestion. It is sold by prescription as Xenical or over-the-counter as Alli. Liraglutide improves blood sugar control and promotes weight loss.

    A Danish study found that Liraglutide caused greater weight loss, decreased blood pressure, and improved blood sugar control better than orlistat or a placebo (fake drugs). Subjects were asked to decrease food intake by 500 calories per day and increase daily physical activity during the 20-week study. Some subjects in the Liraglutide group experienced nausea and vomiting, but the side effects were temporary and did not cause people to drop out of the study.

    Liraglutide is an effective drug for promoting weight control and metabolic health. It is currently approved in Europe but not in the U.S. (Lancet, in press; published online October 2009)

    Inadequate Sleep Linked to Obesity and Physical Inactivity

    The recession has led to increased stress, overwork, and reduced sleep. In addition to triggering fatigue, inadequate sleep makes it more difficult to exercise, which promotes obesity. A review of literature by Sanjay Patel from the Case Western Reserve University in Cleveland, Ohio concluded that inadequate sleep promoted obesity, even in people without sleep apnea (obstructive breathing during sleep).

    Sleep duration has decreased by 15 percent since the 1950s, and 16 percent of Americans get less than six hours of sleep per night. Large population studies showed a clear inverse relationship between hours of sleep and the incidence of obesity. However, in spite of the relationship, we cannot say for sure whether inadequate sleep causes obesity.

    Donald Watenpaugh from the University of North Texas Health Science Center in Fort Worth, Texas, said that humans evolved as athletes who sleep 8 to 9 hours per night. Interfering with sleep decreases exercise capacity and threatens metabolic health, which leads to obesity. Sleep is essential to normal energy balance and weight control. (Current Sports Medicine Reports, 8: 331-338, 2009; Obesity Reviews, 10 (supplement 2): 61-68, 2009)

    Eating Quickly Stimulates Overeating

    Your mother told you to chew your food slowly and enjoy your meal. Many overstressed people often try to eat their food as quickly as possible. They should have listened to their mothers. Greek researchers found that eating a meal quickly decreases hormones in the gut that signal the feeling of fullness to the brain. This can cause overeating.

    During the study, the subjects ate a large bowl of ice cream at different rates and measured the hormones PYY and GLP-1, which help signal the feeling of fullness to the satiety center in the brain. People had higher levels of the hormones and felt more full when they ate the ice cream slowly. Eating meals more slowly may be a simple way to cut down on food intake and decrease body fat. (Journal Clinical Endocrinology Metabolism, in press; published online November 4, 2009)

    Two-a-Day Workouts Increase Fat Use

    Exercising below 65 percent of maximum effort uses mainly fat as fuel. Above this intensity, carbohydrates become increasingly important, and they're used almost exclusively for fuel at extreme exercise intensities.

    Swiss researchers found that fat use during exercise is influenced by prior physical activity. Moderately-trained subjects took two maximal treadmill tests: one to determine maximal oxygen uptake and estimate fat use and a second to determine the effects of prior exercise on fat use. During the second test, subjects exercised on a treadmill for one hour at 57 percent of maximum effort. After a short break, they took the second treadmill test to exhaustion. Fat use was higher when the subjects took the test after the initial one-hour run. Two-a-day workouts will trigger more fat-burning during the second workout.

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    Re: MD Fat Bytes

    Bodybuilding has experienced a number of quantum leaps. Once upon a time, it was mustachioed men clad in unitards performing calisthenics. The introduction of dumbbells and barbells produced mustachioed men in unitards lifting weights that looked more like car parts. Eventually, organized gyms evolved, mustaches were shaved and the unitards were trimmed down to tiny trunks.

    The changes evoked by training methods and facial hair styles were minimal compared to the dramatic changes seen during the last few decades. Eugene Sandow is a legend among early bodybuilders. A strongman who displayed his physique during the late 1800s and early years of the 1900s, Sandow is best known now as the figure personified in the Sandow trophy handed out each year to the winner of the Mr. Olympia. Despite his glorious reign as one of the founders of modern bodybuilding, Sandow’s physique would have been easily overshadowed by most of the bodybuilders of the 1960s and 1970s. It was during this period that physiques were augmented through the use of anabolic steroids. Placing Sandow next to Arnold or Mike Mentzer in their prime would have made Sandow look like a child.

    Then hGH Arrived on the Scene

    During the 1980s, a new drug trickled into the bodybuilding pharmacopoeia that greatly exaggerated the physiques appearing upon the stage: human growth hormone (hGH). It was not until the later 1980s that the use of hGH became relatively commonplace, but it’s now considered a mandatory ingredient for professional bodybuilding success.1 Not only has hGH inflated muscle size, but it has also allowed bodybuilders to strip body fat down to cartoonish levels. The difference has been so great as to physically dwarf even Arnold of the 1970s. Other drugs, such as insulin, aromatase inhibitors and synthol, have added further changes, but hGH is definitely the most potent factor since testosterone esters.

    As noted, the benefits of hGH included both an anabolic effect (bigger muscles) and a lipolytic effect (less body fat), though scientists will dispute the fact that this offers any benefits to athletes.2 Obesity specialists have noted the lipolytic effect of hGH and found it’s effective in treating overweight and obese people.3-6 However, using hGH is not without problems. If too high a dose is administered over a period of time, IGF-1 levels will exceed the therapeutic range and symptoms of hGH excess will develop. Edema, carpal tunnel syndrome, impaired glucose tolerance, enlarged organs, distorted facial features and even overt diabetes can arise if hGH is dosed inappropriately.7-9 Given the political backlash coming against hGH due to its role in sports doping, along with the expense of treatment and monitoring, the possibility of introducing hGH into standard treatment protocols for obesity seems remote. However, there is some promise looming on the horizon.
    Growth hormone is a large protein.10 Proteins are long chains of amino acids that fold and wrinkle so certain parts are exposed on the surface, while others are crumpled up in the middle.11 Of the parts that are exposed, certain amino acid sequences are specifically structured to interact with receptors on the surface of cells. Though most people are taught to consider hormone and receptor interaction as a lock-and-key model, it appears that is oversimplified, at least for protein hormones. Rather than being a single key, large protein hormones like hGH seem to behave more like key rings, with two or more segments able to interact with different cells, bringing about a spectrum of biological effects, rather than a single effect.

    For instance, hGH is known to interact with growth hormone receptor imbedded in the cell surface of fat cells, causing them to break down and release stored fats.12 It also interacts with the liver and other cells to signal the production of growth factors, such as the somatomedins and IGF-1. Different cells, different effects, same hormone.13

    It has long been suggested that hGH behaves like a prohormone in addition to being a direct hormone.14 Small fragments are generated in the peripheral metabolism of hGH, some of which may retain biological activity.15 Researchers have long looked at the activity of various structural segments and discovered separate functions of hGH segments.15,16 One researcher, Dr. F. Ng of Monash University, identified a specific segment located at one end of hGH that appears to be responsible for much of the lipolytic activity.15,17-28 This amino acid sequence interacts with the fat cell, stimulating the breakdown and release of stored fatty acids and glycerol (the components of stored fats or triglycerides).

    Surprisingly, this effect does not appear to involve the hGH receptor. One study measured a significant increase in B3-adrenoreceptors in mice, a receptor for adrenaline and norepinephrine that stimulates fat loss; increases in B3-adrenoreceptors are seen with the use of hGH, as well.27,29 This fragment retains its ability to stimulate fat loss, even after being broken off the larger hGH molecule. It is a peptide chain of only 15 amino acids being developed by the Australian company Metabolic Pharmaceuticals Limited under the code name AOD9604.30

    AOD9604: Exciting Potential
    AOD9604 offers exciting potential to the fat loss arsenal for three primary reasons. First, being a small peptide, the fragment can be administered orally (swallowed), as opposed to hGH which must be injected under the skin.31 Second, it has been shown to be effective at a low dose, which makes it affordable and convenient. Third, it has no anabolic effect, meaning it does not increase IGF-1 or cause muscle or organ growth. Bodybuilders may see the last as a negative, but in fact, it may be a positive as it would likely allow AOD9604 to be approved for use in treating obesity before hGH, as the abuse potential and the risk of side effects would be much lower.

    Dr. Ng collaborated with Metabolic Pharmaceuticals Limited to further investigate the potential of AOD9604 in treating obesity. Together, they have advanced AOD9604 through phase 2b of drug development, demonstrating the effectiveness of the drug in reducing weight of obese subjects.

    Prior studies involving AOD9604 included a number of bench top experiments and animal studies, demonstrating the ability of the drug to stimulate the release of stored fat from fat cells observed in a test tube, as well as reducing weight gain in growing mice.15,17-28,31

    In a 12-week placebo controlled study, groups of obese people were treated with five different levels of AOD9604 along with general diet and exercise advice.32 Three hundred subjects were involved in the study. During the study, no adverse side effects were noted and the test subjects lost more weight than the control group. The most significant weight loss occurred with the group taking the lowest dose of the drug, which is surprising in some aspects. However, this effect had been noted in the earlier studies. The company’s press release stated that one milligram of AOD9604 is actually the biologic equivalent of a very high dose of hGH.30

    Additional benefits of AOD9604 treatment were observed during the study. Changes in cholesterol were charted that would decrease cardiovascular risk, including a decrease in LDL (bad) cholesterol and an increase in HDL (good) cholesterol. Glucose tolerance, a measure of how well the body handles sugar, was also improved. Impaired glucose tolerance is often seen in obese people and is often a warning sign of future diabetes. Even though the actions of hGH are known to stimulate the production of IGF-1, a potent growth mediator, no changes in IGF-1 levels were noted in any of the groups. This further demonstrates that separating the lipolytic effect from the anabolic effect of hGH was achieved.32

    The successful trial of AOD9604 opens an avenue of opportunity, but first the drug must complete the FDA approval process in order to be cleared for worldwide marketing. This will involve a larger study, which is projected to begin later this year. Though it has taken nearly 30 years to reach this point, it appears this drug may become available as a treatment option for those needing help with weight management. If the B3-adrenoreceptor effect is seen in humans, then adding a sympathomimetic combination like ephedrine/caffeine could further increase the effect of treatment.

    What’s in it for the Bodybuilder?

    To the competitive bodybuilder, separating the anabolic effect out of hGH may seem sacrilegious. Considering the impact hGH has had on the sport of bodybuilding, it’s unlikely any serious competitors would opt for AOD9604 as opposed to Nutropin (synthetic hGH). For those who might be satisfied with a less exaggerated physique, but desire a leaner appearance (not to mention better cholesterol levels), AOD9604 may one day be a legitimate option. Being able to avoid daily injections by taking AOD9604 as a tablet will increase its appeal compared to hGH for many. It is unlikely that hGH will be approved for cosmetic or performance purposes any time in the near future. Perhaps by piecing out the valuable parts of hGH, society will be able to access the therapeutic potential of this potent hormone.

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