<p>mini, but which one is causing the other? Are there any other parameter(s) involved?</p>
<p>[STATS.org</a> - What is the difference between causation and correlation?](<a href=“http://www.stats.org/in_depth/faq/causation_correlation.htm]STATS.org”>http://www.stats.org/in_depth/faq/causation_correlation.htm)</p>
<p>^^A must read article.</p>
<p>It is true that psychotropic meds ( and others) can cause weight gain.
I expect it is multi casual. Some may interfere with metabolism & digestion, some may simply affect hunger/blood sugar. ( I think they also cause water retention)</p>
<p>My mother was on several such medications for the last 20 years of her life, and while she had never been lanky, the weight gained in her abdomen also compromised her heart & lung function, a great deal which affected her ability to exercise. ( even to walk & she was not obese- she probably weighed not much more than what I do- which is within BMI, but I have more muscle & she was taller)</p>
<p>I know some of the meds were probably necessary to some extent, but IMO, weight gain is not considered enough of a problem by many prescribing physicians to look for alternatives. I think even Drs. often consider weight gain to be something easily within the patients control & not a contraindication.</p>
<p>
</p>
<p>In my case, the weight gain is but a small price to pay for sanity. Ironically, I looked much healthier when I was in my late teens/early 20s depressed out of mind, living on diet coke and cigs.</p>
<p>Of course, I’d prefer to not have weigh gain be an issue but compared to side effects that make it impossible to stay on meds, it’s not so bad. For me, the rest of my numbers (blood pressure, etc.) are perfect, so that makes it easier to deal with the weight gain as well. </p>
<p>I do get frustrated with mental health professionals, and this is the majority of them in my experience, who seem to truly believe that weight gain is an individuals lack of willpower and do not have much in the way of helpful information.</p>
<p>Endokrynol Pol. 2011;62(3):258-62.</p>
<p>The role of leptin in the regulation of carbohydrate metabolism.
Tucholski K, Otto-Buczkowska E.</p>
<p>Abstract</p>
<p>The hormone leptin is secreted from white adipocytes, and serum levels of leptin correlate with adipose tissue mass. Leptin was first described as acting on the satiety centre in the hypothalamus through specific receptors (ob-R) to restrict food intake and enhance energy expenditure. Leptin plays a crucial role in the maintenance of body weight and glucose homeostasis hrough central and peripheral pathways, including regulation of insulin secretion by pancreatic b cells. Leptin may also directly affect the metabolism and function of peripheral tissues. Leptin has been implicated in causing peripheral insulin resistance by attenuating insulin action, and perhaps insulin signalling, in various insulin-responsive cell types. Research has demonstrated a significant relationship between leptin and insulin, but the mechanisms underlying the changes of leptin induced by insulin, and vice versa, remain to be studied in more detail. Recent data provides convincing evidence that leptin has beneficial effects on glucose homeostasis in mouse models of insulin-deficient type 1 diabetes mellitus. Our study suggests that leptin could be used as an adjunct of insulin therapy in insulin-deficient diabetes, thereby providing an insight into the therapeutic properties of leptin as an anti-diabetic agent. Safety evaluation should include a careful assessment of the effects of this combination therapy on the counterregulatory response to hypoglycaemia. The role of leptin in alpha-cell function has not been studied in detail. Extensive studies will be needed to determine the long-term safety and efficacy of this therapy. (Pol J Endocrinol 2011; 62 (3): 252-261).</p>
<p><a href=“http://www.endokrynologia.polska.viamedica.pl/en/zamow_art_pdf.phtml?id=43&indeks_art=603[/url]”>http://www.endokrynologia.polska.viamedica.pl/en/zamow_art_pdf.phtml?id=43&indeks_art=603</a></p>
<p>Here’s (to me) a more simplified explanation of Leptin and the relationship to diabetes/ insulin resistance:</p>
<p>[Leptin</a> Hormone & Supplements: Do They Work for Obesity & Weight Loss?](<a href=“http://www.webmd.com/diet/features/the-facts-on-leptin-faq]Leptin”>Leptin Hormone & Supplements: Do They Work for Obesity & Weight Loss?)</p>
<p>I just downloaded ‘Mastering Leptin’ on to my Kindle. Am curious to see what it has to say. Had lots of good reviews.</p>
<p>Thanks, MomLive. Very interesting!
This Robert Lustig is doing some fascinating work and trying to connect the dots. I hope other MD’s are listening, and that others start to do even more research about leptin, insulin, and the other hormones and neur-endocrines.
This, to me, is the future of medicine (and Health!). And this area is full of mysteries still.</p>
<p>jsanche,
This study’s implications ARE interesting. Do you think they somehow contradict or countervail the concept of leptin resistance or provide a route to get around it? The concept that insulin reduction is the best way to activate leptin?</p>
<p>MomLive: I hope you paid very good attention to what the article in your link said:</p>
<p>
</p>
<p>and:</p>
<p>
</p>
<p>Just like any hormone of protein nature, leptin has to be administered by injection, just like insulin or human growth hormone. There are **NO FDA-approved leptin medications **on the market, so anyone who is claiming to have one is making fradulent statements.</p>
<p>If anyone wants to read more about leptin than just an abstract from a Polish journal posted by jsanche, here is a full-text review article published by Harvard researchers and their collaborators:</p>
<p>[Leptin</a> in Human Physiology and Therapeutics](<a href=“Leptin in Human Physiology and Therapeutics - PMC”>Leptin in Human Physiology and Therapeutics - PMC)</p>
<p>BB…I saw that. From what I gather, attempts to use Leptin to treat obesity have not panned out. Nor is there a supplement. I just thought the book looked interesting as one more piece of the hormone puzzle.</p>
<p>Yes, there is a route to get around Leptin issues for most dieters.</p>
<p>What normally happens in any diet is that eventually leptin levels drop (Due to loss of bodyfat i.e. body sensing that whole body energy stores have changed, as well as short-term sensors that notice that you have been eating less calories than expended for X amount of time). This causes T3 levels to drop (Thyroid hormones control whole body metabolism) and fat loss slows down to a crawl. Genetics determines when that happens for people (It could be week 4, week 7 etc…) But it always invariably happens.</p>
<p>The way to get leptin levels back up, and therefore re-normalize all the other hormones that are crucial for dieting, is to do one day of carbohydrate loading. </p>
<p>That means 3-5 grams of carbohydrates per pound of lean bodyweight. For a 200lb male with about 180bs of LB that means 540-900 grams of CHO consumed in 24 hours. On this day you will be obviously eating above maintenance. Protein can be kept at 0.8g/lb and fat should be minimized.(50g or less) (For people with poor insulin sensitivity you would use the lower end of the spectrum (3g/lb). If you have good insulin sensitivity use the higher end (5g/lb))</p>
<p>The whole purpose of the carbohydrate loading for one day is to get through a dieting stall. The high carb day will cause a spike in leptin (Remember that there are SR sensors that measure whole body caloric expenditure-intake), which will have the effect of bringing all the other hormones back up to normal. (Or close to it)</p>
<p>That will work for most dieters. In some rare cases this has not worked because the person in question has a problem with their leptin receptors or has profound leptin resistance. This is pretty rare though.</p>
<p>Exogeneous Leptin (as of right now) doesn’t offer much. It still needs to be studied in detail. You’re better off manipulating Leptin through dietary manipulation.</p>
<p>Leptin is absurdly expensive by the way. We’re talking $10,000/month.</p>
<p>I wonder if taking extra T3 (immediately available version of thyroxine)- as in Cytomel- for a day or two would help get through a plateau caused by the leptin drop.</p>
<p>Still does not really get to the problem of leptin resistance (lots of leptin but not active), so I guess fat loss is the only answer to that.</p>
<p>Are there any studies or trials showing the effect of carb loading to re-ignite fat burning?</p>
<p>There do seem to be a few new “cycling” diets (lo-carb then some carb) out there now, I have noticed.</p>
<p>
</p>
<p>Pure, unadulterated, body-builder, bro’ science nonsense.</p>
<p>T3 helps in some regards. For most dieters T4-T3 conversion slows down (Keep in mind that about 80% of all circulating T3 comes from its conversion via T4 and the de-iodinase enzyme) when they are dieting.</p>
<p>You can measure this by taking your bodytemp every morning via an ear thermometer. Once your bodytemp starts to drop significantly, then you know T4-T3 conversion has slowed down.</p>
<p>You can’t take 25mcgs cytomel for a few days to combat this problem though, because once you stop, you’re back to square 1: Impaired T4-T3 conversion due to dieting. You’d have to continue taking cytomel to overcome the thyroid issue.</p>
<p>That above^^^ is the reason why most properly designed diets are structured on a 4 on/ 2 off approach. You have 4 weeks of dieting followed by 2 weeks of eating at maintenance and then repeat. The 2 weeks diet break allows your hormones to re-normalize.</p>
<p>The leptin issue will only start to creep up on you after an extended period of dieting, or if you’re trying to get very lean. When that happens, the only real solution is carbohydrate loading once every 5-7 days.</p>
<p>Regarding the studies, I’ll try to hunt some down for you (IIRC, there are a few but not many. It is still a new concept)</p>
<p>Interesteddad, I have explained why it works. If you think that I am wrong, you better be able to back up your assertions with actual science.</p>
<p>The “I think you’re wrong” explanation is quite simply not going to fly.</p>
<p>No. Homey don’t play dat game. You are the one making the outrageous claim that somebody on a fat loss diet should eat 500 to 900 grams of carbohydrates one day each week. Thus, it is for you to back that up by telling us which body-builder bro’ science nutritional guru you are using as your reference for this “refeed” nonsense.</p>
<p>Impact of short-term high-fat feeding on glucose and insulin metabolism in young healthy men.</p>
<p>Brøns C, Jensen CB, Storgaard H, Hiscock NJ, White A, Appel JS, Jacobsen S, Nilsson E, Larsen CM, Astrup A, Quistorff B, Vaag A.
Source</p>
<p>Steno Diabetes Center, Niels Steensens Vej 1, 2820 Gentofte, Denmark. <a href=“mailto:chbe@steno.dk”>chbe@steno.dk</a>
Abstract</p>
<p>A high-fat, high-calorie diet is associated with obesity and type 2 diabetes. However, the relative contribution of metabolic defects to the development of hyperglycaemia and type 2 diabetes is controversial. Accumulation of excess fat in muscle and adipose tissue in insulin resistance and type 2 diabetes may be linked with defective mitochondrial oxidative phosphorylation. The aim of the current study was to investigate acute effects of short-term fat overfeeding on glucose and insulin metabolism in young men. We studied the effects of 5 days’ high-fat (60% energy) overfeeding (+50%) versus a control diet on hepatic and peripheral insulin action by a hyperinsulinaemic euglycaemic clamp, muscle mitochondrial function by (31)P magnetic resonance spectroscopy, and gene expression by qrt-PCR and microarray in 26 young men. Hepatic glucose production and fasting glucose levels increased significantly in response to overfeeding. However, peripheral insulin action, muscle mitochondrial function, and general and specific oxidative phosphorylation gene expression were unaffected by high-fat feeding. Insulin secretion increased appropriately to compensate for hepatic, and not for peripheral, insulin resistance. High-fat feeding increased fasting levels of plasma adiponectin, leptin and gastric inhibitory peptide (GIP). High-fat overfeeding increases fasting glucose levels due to increased hepatic glucose production. The increased insulin secretion may compensate for hepatic insulin resistance possibly mediated by elevated GIP secretion. Increased insulin secretion precedes the development of peripheral insulin resistance, mitochondrial dysfunction and obesity in response to overfeeding, suggesting a role for insulin per se as well GIP, in the development of peripheral insulin resistance and obesity.</p>
<p>Plasma ghrelin response following a period of acute overfeeding in normal weight men.
Robertson MD, Henderson RA, Vist GE, Rumsey RD.
Source</p>
<p>Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK. <a href="mailto:denise.robertson@oxlip.ox.ac.uk">denise.robertson@oxlip.ox.ac.uk</a>
Abstract
BACKGROUND:</p>
<p>Ghrelin, a 28 amino-acid peptide secreted primarily from the stomach has been identified as the endogenous ligand for the growth hormone secretagogue receptor. Ghrelin is suppressed in the postprandial state and has been linked to both type II diabetes and obesity.
AIMS:</p>
<p>To investigate the effects of a period of overfeeding with high-fat dietary supplements on plasma ghrelin levels in nonobese men.
METHODS:</p>
<p>Six healthy males (21-34 y; BMI 21-24 kg/m(2)) underwent the dietary intervention after completing diet and exercise diaries for 7 days. For 3 further weeks subjects followed their own diet diary supplemented with 125 ml single cream and 50 g roasted peanuts (88 g fat, 15 g Protein, 8 g carbohydrate) every day. Oral fat tolerance tests (OFTT) were undertaken at baseline, 7, 14 and 21 days of fat supplementation. The diet was increased in energy by 3.9 MJ/day and from a mean of 29-45% energy intake from fat with a small weight gain noted each week (P=0.009).
RESULTS:</p>
<p>Ghrelin concentrations were significantly reduced during the baseline OFTT. The postprandial ghrelin response (AUC) was significantly reduced following 2 weeks of dietary supplementation (P=0.005) increasing the suppression of plasma ghrelin by 18% despite only a 3% increase in body weight. Plasma triacylglycerol (P=0.009) and leptin (P=0.035) concentrations were also elevated and postprandial pancreatic polypeptide levels decreased (P=0.038) following dietary-supplementation.
CONCLUSIONS:</p>
<p>These results suggest that the metabolic profile associated with obesity, including a reduction in plasma ghrelin levels, may be related to recent dietary energy intake and precedes the development of significant adiposity.</p>
<p>Effects of short-term carbohydrate or fat overfeeding on energy expenditure and plasma leptin concentrations in healthy female subjects.</p>
<p>Dirlewanger M, di Vetta V, Guenat E, Battilana P, Seematter G, Schneiter P, J</p>
<p>BTW, 500 to 900 grams of carbohydrate is 2000 to 4500 calories. Only in the bro’ science fantasy-land of steroid using body-builder bulk and cut nutrition advice can anyone actually believe that a day of ultra high calorie consumption is an effective fat loss strategy.</p>
<p>And, oh by the way, I’m 16 months into my diet and still waiting on that plateau.</p>
<p>Response of leptin to short-term and prolonged overfeeding in humans.
Kolaczynski JW, Ohannesian JP, Considine RV, Marco CC, Caro JF.
Source</p>
<p>Department of Medicine, Jefferson Medical College, USA.
Abstract</p>
<p>As one of the postulated roles of the ob gene product, leptin, is regulation of energy balance and preservation of normal body composition, we investigated the effect of acute and chronic calorie excess (weight gain) on serum leptin in humans.** Two protocols were employed: 1) acute (12-h) massive (120 Cal/kg) voluntary overfeeding of eight healthy individuals; and 2) chronic overfeeding to attain 10% weight gain, with its subsequent maintenance for additional 2 weeks, involving six normal males. In the acute experiments (protocol 1), circulating leptin rose by 40% over baseline (P < 0.01) during the final hours of overfeeding; this increase persisted until the next morning. **At the point of achievement and the 2-week maintenance of 10% weight gain (protocol 2), a more than 3-fold rise in the basal leptin concentration was observed (P < 0.01). A direct linear relationship was found between the magnitude of the leptin response to weight gain and the percent gain of body fat (r = 0.88; P < 0.01). In summary, 1) in contrast to normal food intake (8), short term massive overfeeding is associated with a moderate elevation of circulating leptin levels that persists until next feeding cycle is initiated; and 2) a 10% weight gain causes different changes in the body composition, and the resulting rise in circulating leptin parallels the increase in the percentage of body fat. In conclusion, these studies document acute elevation of leptin in response to positive energy balance and suggest that developing resistance to leptin is associated with bigger fat deposition during weight gain in humans.</p>