L-Cysteine as a Satiety Trigger: Sign. Ghrelin & Appetite Suppression in Rodents & Humans - Which Foods Are High in Cysteine & Will They Really Help You Lose Weight?

Egg whites are among the best dietary sources of cysteine

You've read about the satiety effects of several amino acids, like arginine, lysine and glutamic acid, about which you've read approximately one year ago right here at the SuppVersity (learn more). That cysteine, an semi-essential amino acid that can be biosynthesized in humans from methionine, would have the same effects, however, is news - even for seasoned SuppVersity veterans.

The news comes right from laboratories of London's King's and Imperial College, where McGavigan  and colleagues investigated the effects of oral and intraperitoneal administration of a range of amino acids on food intake in rodents.

Learn more about the effects of your diet on your body composition at the SuppVersity

Only Whey, Not Soy Works for Wheytloss

10 Things You Didn't Know About Whey

Dairy Protein Satiety Shoot-Out: Casein vs. Whey

How Much Carbs Before Fat is Unhealthy?

5 Tips to Improve & Maintain Insulin Sensitivity

Carbohydrate Shortage in Paleo Land

In their preliminary studies, McGavigan et al. identified l-cysteine, a conditionally essential amino acid that acts as a precursor for biologically active molecules such as hydrogen sulphide (H2S), glutathione and taurine, as an anorectic agent. Needless to say that they felt inclined to further investigated the effects of l-cysteine on appetite in rodents and humans and the mechanisms mediating these effects.

Figure 1: The effect of oral administration of L-andD-cysteine in rats (left) and the effect of intraperitoneal (middle)
and oral (right) administration of L-cysteine on 0–1-h food intake during the early light phase after an
overnight fast in male in male C57BL/6 mice (McGavigan. 2014)

As you can see in Figure 1 the administration of different dosages of l-cystein, but not d-cysteine (Figure 1, left), lead to a significant reduction in 0–1-h food intake in the early light phase following an overnight fast. This effect was identical, but required higher dosages of l-cysteine (human equivalent 0.036 or 0.072g/kg when it was administered orally vs. via intraperitoneal injection.

Where do you find cysteine in foods? Egg whites, whey protein (concentrate, Bounous. 1989) beef and milk are the best sources with 1.2g, 1.15g, 1.0g, and 0.72g per 200kcal serving. Cottonseeds, sprouted lentils, soy protein isolate and defatted sunflowers flour are top sources for vegetarians with 0.7g, 0.65g, 0.63g and 0.58g cysteine per 200kcal serving (nutritiondata.com).

Figure 2: L-cysteine suppresses plasma acyl ghrelin levels in rats. Plasma levels of (a) acyl ghrelin and (b) l-r: GLP-1 and PYY, 30 min after oral gavage of water or 4 mmol/kg l-cysteine (n=7–8), (c) acyl ghrelin and (d) l-r: GLP-1 and PYY, 30 min after intraperitoneal administration of saline or 2 mmol/kg l-cysteine (McGavigan. 2014)

Next to the effects on food intake, the rodent study revealed that an increase in respiratory exchange ratio (=more CHO vs. FATs were burnded) and an increases neuronal activation in the rat brainstem without negative behavioral side effects. What the researchers did not observe, though, was an a reduction in gastric emptying that would be the most straight forward explanation for the reduction in food intake. Against that background, the reduced levels of the hunger hormone ghrelin (see Figure 2) appears to be the most likely mechanism by which the l-cysteine gavage may have lowered the animals' food intake.

This hypothesis is supported by the fact that l-cysteine didn't reduce the food intake of the gen. modified mice which overexpress ghrelin (data not shown in Figure 2).

The effects remain significant with repeated administration: Even when the "trick" is repeated thrice daily for five days, the administration of l-cysteine still lead to an acute reduction in food intake and a corresponding decrease in the cumulating food intake over the 5-day study period in rodents - in view of the short study period obviously without reductions in body weight.

Now we all know that mice are no little men. Therefore, the important question that's rightly preying on your mind now is: Did this work in humans, as well? The answer is pretty straight forward: Yes, it did!

Figure 3: 0.07g/kg l-cysteine in 200ml water lead to significant reductions in hunger ratings and acyl-ghrelin in humans as the corresponding dose in rodents (McGavigan. 2014)

As you can see in Figure 3, the administration of either "vehicle" (=placebo) alone or the same 200 ml drink containing 0.07 g kg/1 l-cysteine in a single-blind (participant) randomised order lead to similar decreases in acyl-ghrelin (hunger hormone) and hunger ratings in the healthy men and women who participated in McGavigan's study.

If you haven't done this, already, it's time to check out the results of the previously cited study by Jordi et al. (2013), now | learn more

Bottom line: Luckily, McGavigan et al. did all the work for me and compared the effects of cysteine in the study at hand to the previously reported effects of arginine & co, I referenced in the introduction and found that "l-cysteine is more anorectic than l-arginine and l-lysine." (McGavigan. 2014)

Furthermore, the researchers point out that "[i]f l-cysteine does have a physiological effect on appetite, then it is likely to act in concert with other products of protein digestion, and thus the effects of l-cysteine per se may be difficult to detect." (McGavigan. 2014) In other words, the repeatedly demonstrated satiety effects of high protein diets may - in parts - be mediated by their cysteine content.

In view of the fact that the effects occur at dosages that do not trigger taste aversion or evoke abnormal behaviour, it may even be possible to administer l-cysteine supplements to overweight individuals before every meal to reduce their food intake and trigger (probably) slow, but persistent weight loss. Since the real-world food intake wasn't measured in humans, yet, this would have to be confirmed in future trials, though | Discuss this article on Facebook!

References:

• Bounous, Gustavo, Gerald Batist, and Phil Gold. "Immunoenhancing property of dietary whey protein in mice: role of glutathione." Clin Invest Med 12.3 (1989): 154-61.
• Jordi, Josua, et al. "Specific amino acids inhibit food intake via the area postrema or vagal afferents." The Journal of physiology 591.22 (2013): 5611-5621. 
• McGavigan, A. K., et al. "l-cysteine suppresses ghrelin and reduces appetite in rodents and humans." International Journal of Obesity (2014).

Pre-Meal Protein Ingestion to Improve Glucose Tolerance: Insulin, GIP, GLP-1 - That's the Whey(!) it Works! Plus: Even Pure Glucose Can "Improve Your Insulin Tolerance"

Can a whey protein appetizer really undo the damage of greasy fast food? Probably not, but it's still interesting to see how it affects the postprandial glycemia.

Insulin resistance is the #1 contributing factor to the obesity epidemic and despite the fact the solution is already out there (read more about the necessary lifestyle modifications), it probably won't hurt to know if something as simple as having a high protein "appetizer" before a junky meal could improve blood glucose management even further, right? "Right, 'cause protein is always, good!" Ah, no... I guess the answer is a little more complex than that... Nevertheless, I still suspect that the results, Tina Akhavan and her colleagues from the University of Toronto present in their soon-to-be-published paper in the Journal of Nutritional Biochemistry will be of interest to you.

The study results are interesting, to say the least...

... and that's not despite but rather because the researchers did not use the usual subjects (rodents, obese individuals or elderly people), but young men (aged 18-29) with a BMI of 18.5-29.4 kg/m². In a randomized cross over design (cross over means that every subject got each treatment - obviously in seperate testing sessions), the subjects drank either...

• 300ml of a 10g or 20g whey protein solution, 
• 300ml of a 10g or 20g glucose solution, or
• 300ml of flavored zero calorie water 

The test drinks were consumed four hours after a standardized (junk = Honey Nut Cheerios + Skim Milk + Orange Juice) "breakfast". 30 min later the subjects were served even more junk in form of a *yummy* frozen Pizza from McCain Foods Ltd.

"Cereals", skim milk, pizza... whey alone won't help to counter that

The Pizza had been prepared "according to manufacturer‘s directions". This means that the reduction in glycemia the scientists observed in response to the protein preload were not because the pizza was still frozen... ok, before I produce even more nonsense, let's take a look at what the whey protein and glucose pre-loads did to the subjects blood glucose responses, right?

Figure 1: Glucose and insulin levels after pre-load and after meal (mean of 30-230min); all values expressed relative to water control, i.e. +85% would mean "85% higher than during control trial" (Akhavan. 2013)

If that's not your first visit to the SuppVersity, I probably won't have to explain the mechanism by which the pre-ingestion of whey (and glucose) reduces the Pizza-induced glycemia - do I? Well, I guess I better repeat it briefly:

1. The ingestion of the whey protein triggers a significant increase in insulin - 127% for the 10g and 191% for the 20g dosage.
2. Contrary to the glucose infusion there is no exogenous glucose that could lead to a rapid elevation of blood glucose (cf. figure 1, left → pre-values); the minimal increase you see is produced by gluconeogenesis in the liver.
3. With the elevated insulin levels, the mean glucose levels in the postprandial phase (30min-230min after the pizza ingestion) is lower with both the glucose and whey preload. The effect is however more pronounced with whey than with glucose. The reason should be obvious: The overall amount of glucose that's got to be stored away is lower.

I know it sounds counter-intuitive, but aside from (2) the mechanism is absolutely identical for the glucose trial - with the insulin already being around low (10g) glucose preload can actually lead to lower postprandial glucose levels than the water control (this is probably only true for healthy individuals).

Insulin? Is that all, or is there more to it?

Now that we have gotten the fundamental mechanism by the means of which "glucose-" and "whey-preloading" before eating pizza can ameliorate the blood glucose surge after the meal, let's take a look at the auxiliary data.

Figure 2: GLP, GIP, PYY, CCK and Ghrelin levels before eating the pizza; all values expressed relative to water control, i.e. +85% would mean "85% higher than during control trial" (Akhavan. 2013)

As the data in figure 2 tells you the increased insulin release was brought about and accompanied by profound increases in the production of the satiety hormones GLP-1 and CCK, as well as the "insulin trigger" GIP (all these changes occured in the pre-meal = pre-pizza phase, only). Ghrelin and PYY, which play an even more important role in the regulatory process that's supposed to control our energy intake, did not show significant treatment dependent differences, though.

What's the practical relevance of these findings? Honestly, I am not sure how relevant the findings from the study at hand actually are. I mean, from a "do this" or "don't do this" point of view - not from a "understanding how things work" perspective.

SuppVersity Suggested Read: "The Satiating Truth About Proteins and Why High Protein and Low Amounts of Low GI Carbs May Not Mix As Well As Most People Think" | read more

For those who would benefit most from reductions in postprandial glycemia, i.e. the obese type II diabetic, it is questionable whether (a) the mean 7% decrease is actually making a difference and whether it would (b) even occur in someone who is having a hard time producing enough insulin to have his / her body react to it.

For the lean individual, on the other hand, the 7% reduction in gylcemia probably doesn't matter at all and the insulin spike before the onslaught of a the "perfect storm" of carbs and fats from a greasy frozen pizza could (worst case scenario) increase the chance of fat storage - I mean the glucose can go to the muscle (learn more), the fat, on the other hand must end up in your adipose organ.

I would thus strongly advice everyone to stick to my "get 30g of quality protein with every meal" recommendation, instead of turning it into a "get 30g of protein before every meal". Aside from the questionable benefits of having the protein before your meal, having it with / as part of your mwal will also direct you away from pizza and towards healthier food choices. After all, you will be hard pressed to find a pizza with 30g+ of protein in it... and I bet the novel "pizza on a stick" I told you about on Facebook, recently, probably doesn't qualify either ;-)

References:

• Akhavan T et al. Mechanism Of Action Of Pre-Meal Consumption Of Whey Protein On
  Glycemic Control In Young Adults. The Journal of Nutritional Biochemistry. October 2013 [accepted manuscript]

The Satiating Truth About Proteins and Why High Protein and Low Amounts of Low GI Carbs Don't Mix Well

So can you? I mean, can you really get rid of hunger pangs by upping the protein content of your meals? Yes, you can, but as usual, there is a string attached, here. One of the infamous "on the other hands", as Carl Lanore likes to call them.

Despite the fact that I actually have to stop some of you from eating too much protein [I am not talking about ill health effects, but a saturation effect for the benefits with 2-3x the RDA, here; cf. "1.6-2.4g/kg Protein Turn Short Term Weight Loss Intervention into a Fat Loss Diet" | read more ], the obese majority of the inhabitants of the Western Obesity belt would certainly benefit from a couple of extra grams of protein in their diets.

One of the reasons protein can help you get and stay lean relates to its profound satiety effects; effects, which have recently been reviewed by a group of researchers from the State Key Laboratory of Cardiovascular Disease at the Fuwai Hospital in Beijing, China (Yang. 2013)

Higher satiety, lower glucose and ghrelin spikes...

... these are the most significant observations the scientists made, when the surveyed the PubMed, Cochrane library, EMBASE, and HighWire Press data bases to identify randomized, crossover trials that investigated the acute effects of isocalorically prescribed high versus normal protein test meals on satiety and ghrelin. Starting out with a total of 1,858 potentially relevant articles the scientists narrowed their selection down to 123 by removing duplicates and studies that did look like they would qualify, but turned out to be off-topic upon closer scrutiny. Of those 123 they eventually dropped another 103 articles based on detailed evaluation, including inadequate data, lack of NP groups, ghrelin administration related study, long-term HP diets and others. That left Yang et al. with 20 studies in total and a couple of interesting results.

Figure 1: Satiety effects (left) and corresponding decreases in the ghrelin AUC in the subjects of the studies under scrutiny in response to high vs. normal protein meals (Yang. 2013)

As you can see in figure 1 the effect size may differ, but with the exception of the 2011 study by Makris et al. the effects were highly beneficial. So what was it about the Makris study that could explain the difference? Well let's see... what are we talking about here? Was there something "wrong" with the breakfast (= test meal)? It consisted of a small scrambled egg and oatmeal prepared with butter and water, sweetened with sugar, and topped with slices of fruit. In order to achieve a lower GI, ...

"[o]ld Wessex instant oatmeal, dextrose, and slices of a semi-ripe banana were used for the high GI meals. McCann’s steel cut oatmeal, fructose, and slices of a Granny Smith apple were used for the low GI breakfasts." (Markris. 2011)

And to get the protein up in the HP conditions, casein powder was added to the scrambled eggs and oatmeal in the high protein condition to increase the protein content from ~14% to 28% of total energy. I see nothing wrong, here, and the same goes for the macronutrient profiles (see table 1).

Table 1: Nutrient content of breakfast meals and amount of water served with the meal (Makris. 2011)

Basically, we have a ~1/2 ratio of protein in the normal vs. high protein arm of a study comparing LGI/normal, HGI/normal to LGI/high and HGI/high protein meals and if we take a close look at the individual results it turns out that no high protein per se, but rather the glorified combination of high protein + low GI carbohydrates appears to be the underlying problem here.

The combination of low GI foods and high protein can make you ravenous

I know it sounds impossible, but in the end, it's logic. Spiking insulin (>50% more insulin in the high protein + low GI vs. the normal protein + low GI arm of the study) in the absence of glucose will make you freakin' hungry (and yes, casein is almost as insulinogenic as whey, learn more). For the subjects in the Makris study this effect was so pronounced that the subjects in the low GI + high protein arm of the study ate ~1800kcal while those in the low GI + normal protein arm consumed only ~430kcal on the subsequent lunch...

Figure 2: Energy intake during lunch after breakfast with high/low GI carbs & high/low amounts of protein (Makris. 2011)

...by the way, did I mention that the high GI + high protein arm displayed the greatest practically relevant satiety effect with a caloric intake of only ~1,300kcal during lunch? I did not? Well it would have been in figure 2, anyway.

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High or low GI, carbs in the morning or in the evening, cookies and dingdongs or all bran. Many questions and too many questionable answers from studies on rodents or diabetics and questionable nutrition experts all around the web .. So what are Mr. and Mrs. Healthy-And-Athletic-Average-Joe supposed to do low GI, low carb, low [...] ? (learn more)

Bottom line: The synergy of high protein, high GI carbs in terms of practically relevant increases in satiety that was observed of all things in the study by Makris et al. the only one with an "on average" negative effect of high protein intakes on satiety in the meta-analysis by Yang et al., may in fact be the reason why simply upping your protein intake has proven time and again to help sugar addicted overweight individuals to shed weight and body fat. After all, they are the ones who live on high GI carbs, anyways.

That being said, the 30g/per meal strategy still is an appropriate and simple nutritional strategy both lean and overweight people can benefit from. Larger amounts of low GI carbs, a non-insulingenic protein source, like steak, or a simple mixture of fast and slow carbs all may solve or at least ameliorate the "hunger problem" and help you to lose body fat, stay lean, build muscle and maintaining muscle mass on a diet (see "Protein Timing Reloaded" | learn more).

References:

• Makris AP, Borradaile KE, Oliver TL, Cassim NG, Rosenbaum DL, Boden GH, Homko CJ, Foster GD. The individual and combined effects of glycemic index and protein on glycemic response, hunger, and energy intake. Obesity (Silver Spring). 2011 Dec;19(12):2365-73. 
• Yang D, Liu Z, Yang H, Jue Y. Acute effects of high-protein versus normal-protein isocaloric meals on satiety and ghrelin. Eur J Nutr. 2013 Jul 4.

Low Vitamin D & Insulin Resistance; Ghrelin Response to Overfeeding; Glutamine for the Elderly; 5g/Day Creatine for Women; MSM for GH Activity in Bone; Curcumin for Burns

Vitamin D research hyper-inflation - unfortunately few of the papers will ever be printed, otherwise we could at least use them to heat our homes, in case the price for oil gas and other fossil energy keep rising ;-)

The SuppVersity Figure of the Week is "1614"! That's the number of studies with the exact phrase "vitamin D" in their title that have been published in the past 9 months and 14 days of the year 2012 (more than five papers per day!). Compared to 1,453 papers in the year 2011 and 1,169 papers in 2010. Projected onto the rest of the year that's going to be a +40% increase in mostly redundant papers! I mean, let's be honest, we have not made any significant scientific progress in the area of vitamin D research over the past months: We have still no idea where the associations end and the causations begin and are more or less clueless as to why vitamin D supplementation simply does not yield any of the beneficial results it is supposed to.

And as if that was not already bad enough, due to the advent of an infinite number of second-class online journals that made the vitamin D paper hyperinflation only possible, most of these papers will never be printed. Otherwise I'd suggest we put them to some good use and burn them like the woman in the image on the right was burning paper money during the days of monetary hyperinflation, over here in Germany in the years 1922 - 1923 ;-)

Vitamin D and insulin resistance 

Having low levels does only make a difference, if you are obese. That's the result of the most recent analysis of data from the MONICA10 cohort consisting of 2656 participants (men and women aged 41–71 years) who participated in a 10-year follow-up examination during 1993–1994 as part of a population-wide survey in Denmark (cf. figure 1; data adjusted for sex, season of blood collection, history of CVD, family history of diabetes, physical activity during leisure time, healthy food index, fish intake, supplement use, smoking status, alcohol intake and educational level):

Figure 1: Risk of incident diabetes associated with serum 25(OH)D and waist circumference categorized as normal, overweight and obese (data based on Husmemoen. 2012).

"Low serum 25(OH)D was associated independently with incident diabetes. The inverse association was only found in overweight-obese and not in normal weight individuals, suggesting that obesity may modify the effect of vitamin D status on the risk of diabetes." (Husmemoen. 2012)

These results stand in line with previous research you've read about here at the SuppVersity suggesting that rather than the absolute 25-OHD levels, which are indicative of your "vitamin D reserves", an obesity induced disruption in the management / metabolism of the "sunshine vitamin" appears to be the real culprit that's behind the associations (not causations!) between low vitamin D levels and the metabolic syndrome.

That this problem can't be solved by simply adding more vitamin D to the equation stands to reason and would also explain why the few controlled vitamin D3 supplementation trials in non (morbidly) obese, highly vitamin D deficient individuals that exist did not bring about any of the metabolic benefits the researchers had expected.

Supplemental glutamine prevents non-sarcopenic age-induced weight loss 

We usually think of being overweight, when we talk of "weight problems". For older people it is yet often rather the opposite. Many are losing weight and start to literally wither away. And while glutamine does not help with the muscular aspect (strength training and at least 20g of EAA-rich proteins with every meal), it could at least help with making the most of the food you eat and the supps you take.

While the mechanism is not yet fully elucidated, the results of a recent study by Meynial-Denis et al. clearly suggest that the provision of supplemental glutamine effectively prevents the loss of body weight. A possible mechanism my be related to its concomitant (or upstream?) effects on the integrity and function of the enterocytes in the gut lining of the very old rats the researchers used as a model (Meynial-Denis. 2012).

Therefore I am not convinced that the researchers hypothesis that these effects are brought about by

1. the ameliorative effects of glutamine on the age-induced CO(2)/glutamate ratio, and
2. the role of glutamate as a precursor for glutathione, arginine and proline biosynthesis,

fully explain the observed effects. And even if they are, the additional (maybe in that case downstream) improvement of nutrient absorption subsequent to the conservation or restoration of a healthy/-ier gut lining can hardly be underestimated. After all, it is becoming increasingly clear that much of the age-induced loss of body weight is at least promoted, if not causally related to the decreased absorption of various essential nutrients.

Unexpected ghrelin response during 7-day overfeeding experiment in obese subjects

"Confusing" would in fact be a better term to describe the surprising finding that 7-days on a diet containing 70% more energy than the 68 healthy young, normalweight, overweight and obese men usually consumed did not reduce, but increase the amount of the acylated form of ghrelin (often touted as the "active" = hunger promoting form of ghrelin), in the blood of the study participants (Wadden. 2012). Moreover, ...

• there was no significant difference in fasting acylated ghrelin between normal weight, overweight, and obese men at baseline and
• the amount of acylated ghrelin was negatively correlated with weight and BMI for normal weight and with BMI in overweight men.

Yet while ghrelin also correlated with the changes in body weight and BMI the study participants experienced in the course of the one-week intervention. It was negative (which is obviously what you should expect) only in he normal- and overweight subjects. In the obses study participants, on the other hand, the correlation was positive, i.e. more weight gain = more ghrelin.

Illustration of the global obesity epidemic (WHO. 2005). The study at hand makes it pretty clear that a pathological dysregulation of energy intake is at least part of the problem.

In other words: While there were no differences at baseline an increase in acetylated ghrelin was associated with lower body weights and weight loss in normal- and overweight subjects, while the obese (=pathologically overweight subjects) showed increases in acetylated ghrelin, when they gained weight.

If we stick to the fundamental hyptothesis that ghrelin is in fact a "hunger hormone" and the acylation, i.e. the addition of an acyl functional group to the basic molecule, works like an "on switch" that activates the appetite increasing effects of ghrelin, this means nothing else than overeating and gaining weight makes obese men hungrier. This finding provides further evidence for the hypothesis that the natural regulation of food intake is not simply impaired, but totally out of whack in obese individuals.

MSM turns out to be a local GH booster and bone builder 

MSM? That's the stuff in the joint supplements, right? Correct! Methylsulfonylmethane (MSM) is a naturally occurring sulfur compound with well-known anti-oxidant properties and anti-inflammatory activities that is a longstanding standard ingredient in joint supplements (next to glucosamine sulfate and chondroitin sulfate - you notice the sulf... ah, pattern here, right?).

I guess you knew all that already, but I would be surprised if you had also been aware of the fact that MSM exerts direct anabolic effects on the bone by increasing the expression of GH-related proteins including IGF-1R, p-IGF-1R, STAT5b, p-STAT5b, and Jak2 in osteoblastic cells and mesenchymal stem cells.

"MSM increased IGF-1R and GHR mRNA expression in osteoblastic cells. The expression of MSM-induced IGF-1R and GHR was inhibited by AG490, a Jak2 kinase inhibitor. MSM induced binding of STAT5 to the IGF-1R and increased IGF-1 and IGF-1R promoter activities. Analysis of cell extracts by immunoprecipitation and Western blot showed that MSM enhanced GH-induced activation of Jak2/STAT5b. [...] Furthermore, MSM increased ALP activity and the mineralization of MSCs." (Joung. 2012)

Unfortunately, in vitro studies like these don't provide any information on appropriate dosages, but a study that was published in August 2012 reports that dosages up to 10-fold higher than the dose equivalent of the 300-400mg/day, which are at the upper end of the spectrum of the dosage recommendations of currently available MSM supplements, lead to "dose dependent" decrease in the degeneration of the cartilage in the knee joints in a mouse model of osteoarthritis (Ezaki. 2012). The hilariously high dose of 30-40g (100x the recommended amount), on the other hand, led to significant losses of body, liver, and spleen weight.

So, even with an acute fracture you better keep your MSM intake within reasonable limits - specifically, because we do not even know if oral methylsulfonylmethane will help with either bone-healing or bone strength in humans, at all.

If muscle is metabolic currency, creatine is the cash machine

"Ehhh! This will make me hold water? No thanks I already got enough of that! And muscle, not thanks..." Shut up! Muscle is metabolic currency and gaining muscle and strength is equally beneficial for the health of men and women, alike.

Against that background you may want to print the results from a recently published paper by Andreo Fernando Aguiar from the North University of Paranay and his colleagues and put the print out somewhere where all, not just the older ladies at your gym will see that taking 5g of creatine /day helped eighteen healthy ladies in their best years (64.9±5.0 years) to

If looking gorgeous and being strong & healthy is your goal, creatine is your supplement of choice, ladies...and gents! Changes in body fat percentage and muscle mass in response to 12-week strength training expressed relative pre value in control group (calculated based on Aguiar. 2012)

• train at a more than 2-fold higher volume,
• make 5.1, 3.9, and 8.8% greater progresss in bench press, leg extension, and biceps curl performance
• gain 3.2% more fat-free mass and 2.8% more muscle mass, and
• be more efficient in performing submaximal-strength

...than the nine women in the placebo group (Aguiar. 2012). With a somewhat higher overall training volume and maybe three instead of just 2 sets of 10-15 reps of

• vertical bench press, lat pulldown, 
• biceps curl, triceps pushdown, 
• knee extension, leg curls, 
• seated calf raises, and abdominal crunches

three times per week and a reduced carbohydrate intake (carbs down by 20% to 45% and protein up by 20% to 40% of the total energy intake) I am pretty sure the ladies in the creatine group would also have been able to turn the hitherto non-significant 2% reduction in total body fat into a significant one.

"Strong is the new sexy" and creatine can help you to get there!

About time to pull the emergency break strength train eat and take creatine?!

In a way it's unfortunate that the ability to promote weight loss is an almost necessary prerequisite for an ergogenic to  be attractive to women. If you can't answer the question "Will it make me lose weight... ah, I mean fat?" with a definitive "Yes, ma'am!", they won't buy it. That said, even with the current training and dietary regimen, the women in the creatine group dropped 1.6% total body fat and, due to the increase in lean mass, decreased their body fat percentage by -2.8%, while the ladies in the control group gained 1.2% body fat (total), so that their body fat percentage effectively did not change at all (+0.4%). Stronger, leaner and healthier! What more can you ask for in a dietary supplement?

Topical curcumin improves wound healing (plus tips how to prepare it)

In view of its profound anti-inflammatory effects it is actually not straight forward that curcumin would improve wound healing - at least not in the early, inflammatory phase of the process. Accordingly the researcher from the Department of Dermatology at the Faculty of Medicine of the Namik Kemal University in Tekirdag, Turkey, divided their burned rodents into 3x2 groups who were scheduled to be anesthetized on day 4 (A), day 6 (B) or day 8 (C) after after they had been burned with an aluminum branding iron that had been placed without pressure for 30s on the back of the rats (Kulac. 2012).

Histopathological scores for inflammatory cells, collagen, deposition, angiogenesis, granulation tissue formation, and epithelialization in each group (based on Kulac. 2012); group A (4th day post burn), group B (8th day post burn), group C (12th day post burn)

The rats in the three treatment groups who had received 200 µl of curcumin at a concentration of 100 mg/kg body weight, topically, once daily, showed increased wound healing during all the critical steps of tissue regeneration, i.e. inflammation, collagen deposition, angiogenesis, development of granulation tissue, and the repair of epithelium.

Interestingly, the inflammatory cell infiltration was significantly increased in curcumin groups and that regardless of when the tissue samples were analyzed. Collagen deposition, angiogenesis and granulation tissue formation were likewise higher in curcumin compared to the placebo group, with the earliest squamous epithelial re-epithelialization being observed on the 4th in treatment subgroup (figure 2, Group A).

Self-made curcumin band-aids / pastes

And in case you don't want to waste money or support Johnson and Johnson by buying the tumeric laced bandages they apparently sell in India, here are two ways to prepare a bandage and a tumeric paste that will probably help with sorts of inflammatory skin conditions (Hinkle. 2012):

In India people use tumeric + honey facial masks; also to treat acne, by the way.

• tumeric wrap / band-aid: Combine one teaspoon of dried turmeric powder with two teaspoons of either dried or fresh ginger. Spread the mixture over a cloth, then wrap around the affected area and seal it with a plastic bandage.
• tumeric paste for burns: Combine one teaspoon of turmeric powder with one teaspoon of aloe vera gel and apply it directly to the burned / inflamed part of your skin (make sure not to apply it directly onto open wounds, though!)

Be careful, though! Tumeric is also a powerful dye that's not easy to wash off again. So whatever towel you may be using as a wrap may therefore be ruined and in case the paste gets in contact with your shiny new white shirt, hot pants or whatever those are likely to be ruined, as well.

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That's it for today, folks. I am not sure whether you feel this is sad or good, but I hope for you, and in a way me and the SuppVersity, that it is the latter, because it may well be that I will increase the frequency of these On Short Notice. In that I will be trying to get even further away from the lengthy items from last week and make them actually short, again ;-)

A pros pos short, those who like these news updates, may also enjoy the weekly SuppVersity Science Round Up that airs live every Thursday at 12.30 or 1.00PM EST, And if you can't tune in live, you can simply have google show you the links to the podcasts of the latest shows.


References:

• Aguiar AF, Januário RS, Junior RP, Gerage AM, Pina FL, do Nascimento MA, Padovani CR, Cyrino ES. Long-term creatine supplementation improves muscular performance during resistance training in older women. Eur J Appl Physiol. 2012 Oct 7.
• Ezaki J, Hashimoto M, Hosokawa Y, Ishimi Y. Assessment of safety and efficacy of methylsulfonylmethane on bone and knee joints in osteoarthritis animal model. J Bone Miner Metab. 2012 Aug 10.
• Hinkle, Lynette. Homemade Remedies With Turmeric. eHow.com - Herbs & Botanicals for Health J-Z. < http://www.ehow.com/way_5402326_homemade-remedies-turmeric.html > retrieved on Oct 13, 2012.
• Husemoen LL, Skaaby T, Thuesen BH, Jørgensen T, Fenger RV, Linneberg A. Serum 25(OH)D and incident type 2 diabetes: a cohort study. Eur J Clin Nutr. 2012 Oct 3. doi: 10.1038/ejcn.2012.134. 
• Joung YH, Lim EJ, Darvin P, Chung SC, Jang JW, et al. MSM Enhances GH Signaling via the Jak2/STAT5b Pathway in Osteoblast-Like Cells and Osteoblast Differentiation through the Activation of STAT5b in MSCs. PLoS ONE. 2012; 7(10): e47477.
• Kulac M, Aktas C, Tulubas F, Uygur R, Kanter M, Erboga M, Ceber M, Topcu B, Ozen OA. The effects of topical treatment with curcumin on burn wound healing in rats. J Mol Histol. 2012 Oct 2.
• Meynial-Denis D, Bielicki G, Beaufrère AM, Mignon M, Patureau Mirand P, Renou JP. Glutamate and CO(2) production from glutamine in incubated enterocytes of adult and very old rats. J Nutr Biochem. 2012 Aug 13.
• Wadden D, Cahill F, Amini P, Randell E, Vasdev S, Yi Y, Zhang W, Sun G. Serum acylated ghrelin concentrations in response to short-term overfeeding in normal weight, overweight, and obese men. PLoS One. 2012;7(9):e45748.

The Female(?) Athlete Triad - Part II/III: LH, GH, IGF1, Insulin, Ghrelin, Leptin & Co Form a Self-Perpetuating Vicious Cycle

I usually rant against pizza and beer, but once the athlete triad has struck, they can be an occasional part of the "healing protocol".

In last Sunday's first installment of this series we have taken a look at the prevalence, etiology and fundamental cause of an entity that is, and I am repeating myself here, profoundly mislabeled as the "female athlete triad". In fact, it is, as we have learned in the last installment, neither an exclusively female thing, nor a triad. If anything, it is a quintet or sextet. To make that clear, and give you guys, who make the same mistakes, but usually with less detrimental consequences, I will once more refer to it as "athlete triad" = AT,  in this second part of the Female(?) Athlete Triad Series in which we will take a look at the endocrine underpinnings of the previously described consequences of the temporary and long-term energy deficiency we have identified as the single most important causative factor of the onset of the "triad" last Sunday.

Which endocrine factors are figuring, here?

Instead of overwhelming you with the details right from the start, I decided to compile a list based on a cross-section of the dozens of articles I have read in the course of my eventually futile quest for a single definitive answer to the question, "Which hormonal or metabolic consequence of restrictive eating and excessive training is to blame for the fatigue, the low sex hormones concentration,the  bone resorption, the anemia, the absence of menses / lack of libido, the performance decreases and the whole string of pathological features, we have explored in the last installment?"

"Refeeding is not an option, because you will only become fat!" FALSE! Yet another myth without substantial scientific foundation that probably arises from the disturbed self-perception of those affected by AT and AN. In fact, the fat stores are the last thing that will be restored (Golden. 2004). This is probably also one of the reasons why "refeeding" often does not appear to work, because the basal energy requirements will increase with every pound of lean tissue you add back to your frame, so that athletes suffering from the "triad" will have to continuously increase their energy consumption. Unfortunately, most athletes will fail to do the former (also because exercise & stress can blunt hunger) and instead react with an increase in workout intensity, now that they are finally able to work out, again. This, in turn, will restore or even exacerbate the energy deficit and thus worsen not improve their physiological problems, even if their scale shows that they have already gained 5-10kg. If you take a look at figure 1 you will also realize that, at least in women, a baseline level of total (not relative!) body fat appears to be necessary to maintain regular menses (in men to maintain normal total testosterone & SHBG, but not so much free testosterone levels or reproductive function).

• low luteinizing levels are unquestionably among the elemental features and causally responsible for the occurance of menstrual disorders / lack of libido and the correspondingly low estrogen and testosterone levels in women and men
• TSH levels are not a valid / reliable indicator for the presence of absence of AT, because they can be both slightly increased or normal in the presence of low T4 and low T3 levels, as  - and this is far more often the case - TSH can be low despite low free thyroid hormone levels (usually in the presence of a low T3/rt3 ratio; if anything this would be a good indicator of beginning or full-blown AT)
• the circadian cortisol rhythm is whacked in men and women, alike; characteristic are the absence of an appropriate cortisol spike in the morning as well as the normal decline in cortisol levels  in the course of the day; metaphorically speaking, as the athletes triad progresses, the "mountain range" turns into mesa and eventually into a plane lowland
• the quartet of (mostly) sub-clinical hypogylcemia, low insulin, extreme high / or totally blunted insulin sensitivity, low IGF-1 and high catecholamine levels cannot be seen in isolation, most detrimental are yet probably the first and last of these four glucose-related players in the AT concert, as the former entails the constant risk to run out of "brain fuel" (in the absence of alternative fuel sources) and can - in the absence of adequate corticosteroid expression - become potentially life-threatening and the latter, i.e. low IGF-1 levels and very low IGF-1 to IGF1 binding protein 4 being one of the, if not the central factor involved in the the long-term physical decline of muscle, bone, organ and even brain mass.

As I have repeatedly emphasized in the last installment, the underlying cause, the trigger, maintaining factor and thus most important setscrew of the athlete triad (female or male) is an over-exaggerated and / or  long-lasting (weeks to months, in the worst case years; see Sundgot-Borgen. 2000) discrepancy between energy intake and expenditure, your body will initially try, but eventually fail to compensate by

• tapping into its energy stores in form of body fat, muscle and organ mass, the insulating fat around nerves and organs, etc.,
• continuously decreasing its metabolic activity (esp. thyroid metabolism),
• shutting down non-vital, but energy-intensive (e.g. immune and reproductive system) bodily functions, to prioritize short term survival of the individual over long-term survival and the conservation of the species

Therefore it is an indispensable and in many cases even sufficient prerequisite to restore an adequate supply of nutrients, and abolish temporarily better reverse the discrepancy between "energy in" and  "energy out" (please read the information in the red box next to the list of the previous paragraph, as well).

And what about leptin, ghrelin, adiponectin ... ?

Figure 1: In female athletes, only total fat mass, not body fat % or BMI are associated w/ AT (here identified by amenorrhea; top, left); the correspondingly low pulsatile (not baseline, see lower left) of LH correlate negatively with ghrelin and positively with leptin (top, right); while LH and leptin show a lack of pulsality, the ghrelin levels are not simply elevated, they also have a higher pulse size, amplitude and total polsatile secretion compared to control and eumenorrhetic athletes (bottom; LH, ghrelin, leptin expressed relative to non-athletic control; based on Ackerman. 2012)

Similar to the facilitative effects of the "hunger high", the "evolutionary advantage" that's turning its ugly face on everyone, who's willing to dig a deep enough whole (see Part I), the endocrine imbalances, as well as the reduced leptin) or over-pronounced (adiponectin) release of adipokines and the disturbances of the glucose, fatty acid and cholesterol metabolism start to take on a life of their own.

And as if that alone would not already make it difficult enough to separate cause and effect, it does actually appear likely that the order may even be reversed over time - not unlike the chicken that will hatch and eventually lay an egg. 

As discussed in the last installment, the combination of over-exercising and fasting, which may at time-point T0 actually have been the root cause of the problem will often turn into a strategy to stave off the impeding total breakdown. It becomes sort of a conditioned response to the constant starvation, which  will then no longer manifest itself in the form of hunger, but as anxiety and an almost compulsive urge to exercise (this is particularly well-established for anorexics; Teufel. 2008). And while the latter can be motivated by the desire to increase athletic performance and/or lose even more body fat, it does have a very real, often under-appreciated, physiological underpinning.

If you like, you could argue that the urge of the starved athlete to exercise is yet another "evolutionary conserved" automatism that mirrors the well-known food-seeking behavior rodents display  in periods of food deprivation and in response to the stimulatory effects of ghrelin on the orexin neurons in the brain (Yamanaka. 2003).

From ghrelin to growth hormone to IGF-1 and back

At the same time, the combination of exercise, low triglyceride, low free fatty acid and exuberant levels of the "hunger hormone" ghrelin leads to an overexpression of growth hormone (Scacci. 2003), subsequent increases in adiponectin (Wölfing. 2008), which will in turn decrease progesterone and androstenedione production and LH receptor expression in ovarian cells (Lagaly. 2008) and GnRH and LH release in the pituitary (Rodriguez-Pacheco. 2007; Lu. 2008). The surprisingly high adiponectin levels (surprisingly in view of the often dangerously low levels of adipokine producing body fat) will further increase the borderline pathological insulin sensitivity and thus lower the already rock bottom blood glucose and basal, as well as (post-)prandial insulin levels even further.

Figure 2: Illustration of the self-perpetuating vicious cycle of the athlete's triad (AT)

With their suppressive effect on leptin (Böni-Schnetzler. 1999), the high growth hormone levels and low body fat reserves are probably the most important contributers to the pathologically low, in fact quasi non-existent basal leptin secretion (see figure 1). And the low insulin levels don't just compromise the normal food-induced prandial suppression of ghrelin (Murdolo. 2003), they also hamper the production of IGF-1 (especially in the liver), so that athletes who suffer from the "triad" cannot derive any anabolic benefits from their high growth hormone levels, since the latter are largely mediated by the stimulatory effect of growth hormone on the production of IGF-1... what you are seeing here is thus a self-perpetuating vicious circle, you can extricate yourself from only by a multi-faceted approach the pillars of which are an..

* in view of the insulinogenic effects of whey and the pro-IGF-1 effects of casein (Hoppe. 2009), and the anti-catabolic effects of CLA & omega-3 you should - if by any means possible - incorporate dairy products from preferably grass fed dairy (butter, milk, cheese, yoghurt, quark / curd cheese, fermented dairy and if you want protein powders) in your diet regularly, better daily.

1. adequate and continuous energy supply to control ghrelin levels and help stabilize blood sugar (and thus glucocorticoid) levels and restore normal leptin and adiponectin expression,
2. increased low GI (to avoid reactive hypoglycemia) carbohydrate and protein intakes to normalize glucose levels, suppress ghrelin, increase insulin and IGF-1 levels* (Foster-Schubert. 2008; suggested read: "Carbohydrate Shortage in Paleo Land"),
3. balanced intakes of all types of natural fats, with an emphasis on long-chain PUFAs from food including a reasonable amount of "bad" omega-6 fatty acids and w/out fish oil or other omega-3 supplements, which would further blunt the already compromised glucocorticoid response and the leptin secretion (Kratz. 2002; suggested read "Omega-3 and Low Cortisol"), and
4. profound reductions in training volume to lower GH, cortisol, catecholamin and energy requirements and a (temporary) reorientation towards low volume strength training that will help increase bone density and IGF-1 expression (Davee. 1990)

Now, this may sound hilarious, but for the time being, laziness, pizza and beer - in moderation - are actually your friends. In that, I am not suggesting that you have to copy the patient, Chris Kresser mentioned several times on the old "Healthy Skeptic" podcasts (now RHR) about a client, who "cured" his longstanding physiological, and as I suspect psychological problems with pizza and beer, but the third pillar of this guy's regimen is actually a must: Go out with friends and start to enjoy your life again! Without thinking about food and exercise and sticking to whatever form of restrictive "diet" all the time.

Figure 3: Development of BMI (blue), leptin (red), adiponectin (green) levels in 8 female adolescent malnourished AN patients (based on Modan-Moses. 2007)

Apropos, third pillar. I have already had my short intense workout for the day, I have eaten well, but I have not hung out with friends. In other words, I will postpone the in-depth discussion of the energy and nutrient requirements, useful and detrimental supplements and medications, as well as necessary and facilitative tweaks to your workout routine to the next week, add another Roman "I" to the second "II" in "Part II/II" in the preliminary headline of this post and leave you (hopefully not too frustrated) with the graphical illustration of the effects re-feeding, alone, and a normalization of the body weight from a BMI of 16kg/m² to ~19kg/m² can have on the skewed basal leptin and adiponectin in figure 3.

In view of the fact that other studies have shown that this increase in weight, which must not be confused with a mere increase in adiposity, i.e. body fat percentage (go back to figure 1 if you already forgot that the absolute not the relative fat mass counts and please remember that the latter includes the fat in the myelin sheaths of your nerves, the protective fat around the organs, the fat in your brain etc.), does help with the normalization of both insulin and ghrelin (Otto. 2001), growth hormone and IGF-1 (Argente. 1997) and is in some cases even sufficient to restore most of the endocrine abnormalities (Scheid. 2010), many of the lessons we will learn in the next (and according to my current plans last ;-) installment can also be applied to a lean bulk - and that goes irrespective of your gender and your whether or not you have already fallen victim to the athlete triad!

References

• Ackerman KE, Slusarz K, Guereca G, Pierce L, Slattery M, Mendes N, Herzog DB, Misra M. Higher ghrelin and lower leptin secretion are associated with lower LH secretion in young amenorrheic athletes compared with eumenorrheic athletes and controls. Am J Physiol Endocrinol Metab. 2012 Apr 1;302(7):E800-6.
• Argente J, Caballo N, Barrios V, Muñoz MT, Pozo J, Chowen JA, Morandé G, Hernández M. Multiple endocrine abnormalities of the growth hormone and insulin-like growth factor axis in patients with anorexia nervosa: effect of short- and long-term weight recuperation. J Clin Endocrinol Metab. 1997 Jul;82(7):2084-92.
• Beals KA, Manore MM. Disorders of the female athlete triad among collegiate athletes. Int J Sport Nutr Exerc Metab. 2002 Sep;12(3):281-93. 
• Boag F, Weerakoon J, Ginsburg J, Havard CW, Dandona P. Diminished creatinine clearance in anorexia nervosa: reversal with weight gain. J Clin Pathol. 1985 Jan;38(1):60-3. 
• Böni-Schnetzler M, Hauri C, Zapf J. Leptin is suppressed during infusion of recombinant human insulin-like growth factor I (rhIGF I) in normal rats. Diabetologia. 1999 Feb;42(2):160-6.
• Caspar-Bauguil S, Montastier E, Galinon F, Frisch-Benarous D, Salvayre R, Ritz P. Anorexia nervosa patients display a deficit in membrane long chain poly-unsaturated fatty acids. Clin Nutr. 2012 Jun;31(3):386-90.
• Davee AM, Rosen CJ, Adler RA. Exercise patterns and trabecular bone density in college women. J Bone Miner Res. 1990 Mar;5(3):245-50.
• Di Carlo C, Palomba S, De Fazio M, Gianturco M, Armellino M, Nappi C. Hypogonadotropic hypogonadism in obese women after biliopancreatic diversion. Fertil Steril. 1999 Nov;72(5):905-9.
• Di Luigi L. Does the high performance athlete need hormone replacement? Endocrine Abstracts. 2012; 29: 35.1 
• Foster-Schubert KE, Overduin J, Prudom CE, Liu J, Callahan HS, Gaylinn BD, Thorner MO, Cummings DE. Acyl and total ghrelin are suppressed strongly by ingested proteins, weakly by lipids, and biphasically by carbohydrates. J Clin Endocrinol Metab. 2008 May;93(5):1971-9.
• Figueiro MG, Plitnick B, Rea MS. Light Modulates Leptin and Ghrelin in Sleep-Restricted Adults. International Journal of Endocrinology. 2012, Article ID 530726.
• Golden NH, Meyer W. Nutritional rehabilitation of anorexia nervosa. Goals and dangers. Int J Adolesc Med Health. 2004 Apr-Jun;16(2):131-44.
• Hernández M, Argente J, Navarro A, Caballo N, Barrios V, Hervás F, Polanco I. Growth in malnutrition related to gastrointestinal diseases: coeliac disease. Horm Res. 1992;38 Suppl 1:79-84.
• Hobart J, Smucker D. The Female Athlete Triad. Fam Physician 2000; 61:3357-64,3367. 
• Hoppe C, Mølgaard C, Dalum C, Vaag A, Michaelsen KF. Differential effects of casein versus whey on fasting plasma levels of insulin, IGF-1 and IGF-1/IGFBP-3: results from a randomized 7-day supplementation study in prepubertal boys. Eur J Clin Nutr. 2009 Sep;63(9):1076-83.
• Khan KM, Liu-Ambrose T, Sran MM, Ashe MC, Donaldson MG, Wark JD. New criteria for female athlete triad syndrome? As osteoporosis is rare, should osteopenia be among the criteria for defining the female athlete triad syndrome? Br J Sports Med. 2002 Feb;36(1):10-3. 
• Klok MD, Jakobsdottir S, Drent ML. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev. 2007 Jan;8(1):21-34.
• Kratz M, von Eckardstein A, Fobker M, Buyken A, Posny N, Schulte H, Assmann G, Wahrburg U. The impact of dietary fat composition on serum leptin concentrations in healthy nonobese men and women. J Clin Endocrinol Metab. 2002 Nov;87(11):5008-14.
• Lagaly DV, Aad PY, Grado-Ahuir JA, Hulsey LB, Spicer LJ. Role of adiponectin in regulating ovarian theca and granulosa cell function. Mol Cell Endocrinol. 2008 Mar 12;284(1-2):38-45.
• Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med. 1995 Mar 9;332(10):621-8. Erratum in: N Engl J Med 1995 Aug 10;333(6):399.
• Loucks AB, Verdun M, Heath EM. Low energy availability, not stress of exercise, alters LH pulsatility in exercising women. J Appl Physiol. 1998 Jan;84(1):37-46.
• Loucks AB. Energy availability, not body fatness, regulates reproductive function in women. Exerc Sport Sci Rev. 2003 Jul;31(3):144-8.
• Lu M, Tang Q, Olefsky JM, Mellon PL, Webster NJ. Adiponectin activates adenosine monophosphate-activated protein kinase and decreases luteinizing hormone secretion in LbetaT2 gonadotropes. Mol Endocrinol. 2008 Mar;22(3):760-71. Epub 2007 Nov 15.
• Manore MM. Dietary recommendations and athletic menstrual dysfunction. Sports Med. 2002;32(14):887-901. 
• Mikos AE, McDowell BD, Moser DJ, Bayless JD, Bowers WA, Andersen AE, Paulsen JS. Stability of neuropsychological performance in anorexia nervosa. Ann Clin Psychiatry. 2008 Jan-Mar;20(1):9-13.
• Miller SM, Kukuljan S, Turner AI, van der Pligt P, Ducher G. Energy deficiency, menstrual disturbances, and low bone mass: what do exercising Australian women know about the female athlete triad? Int J Sport Nutr Exerc Metab. 2012 Apr;22(2):131-8.  
• Modan-Moses D, Stein D, Pariente C, Yaroslavsky A, Ram A, Faigin M, Loewenthal R, Yissachar E, Hemi R, Kanety H. Modulation of adiponectin and leptin during refeeding of female anorexia nervosa patients. J Clin Endocrinol Metab. 2007 May;92(5):1843-7. Epub 2007 Feb 27.
• Mont L, Castro J, Herreros B, Paré C, Azqueta M, Magriña J, Puig J, Toro J, Brugada J. Reversibility of cardiac abnormalities in adolescents with anorexia nervosa after weight recovery. J Am Acad Child Adolesc Psychiatry. 2003 Jul;42(7):808-13.
• Murdolo G, Lucidi P, Di Loreto C, Parlanti N, De Cicco A, Fatone C, Fanelli CG, Bolli GB, Santeusanio F, De Feo P. Insulin is required for prandial ghrelin suppression in humans. Diabetes. 2003 Dec;52(12):2923-7.
• NCAA® Sports Sponsorship and Participation Rates Report • 1981-82 – 2010-11.  
• Orlandi E, Boselli P, Covezzi R, Bonaccorsi G, Guaraldi GP. Reversal of bone marrow hypoplasia in anorexia nervosa: case report. Int J Eat Disord. 2000 May;27(4):480-2.
• Ott V, Fasshauer M, Dalski A, Meier B, Perwitz N, Klein HH, Tschöp M, Klein J. Direct peripheral effects of ghrelin include suppression of adiponectin expression. Horm Metab Res. 2002 Nov-Dec;34(11-12):640-5.
• Otto B, Cuntz U, Fruehauf E, Wawarta R, Folwaczny C, Riepl RL, Heiman ML, Lehnert P, Fichter M, Tschöp M. Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa. Eur J Endocrinol. 2001 Nov;145(5):669-73.
• Rguibi M, Belahsen R. Body size preferences and sociocultural influences on attitudes towards obesity among Moroccan Sahraoui women. Body Image. 2006 Dec;3(4):395-400. Epub 2006 Sep 7.
• Rodriguez-Pacheco F, Martinez-Fuentes AJ, Tovar S, Pinilla L, Tena-Sempere M, Dieguez C, Castaño JP, Malagon MM. Regulation of pituitary cell function by adiponectin. Endocrinology. 2007 Jan;148(1):401-10.
• Scacchi M, Ida Pincelli A, Cavagnini F. Nutritional status in the neuroendocrine control of growth hormone secretion: the model of anorexia nervosa. Front Neuroendocrinol. 2003 Jul;24(3):200-24.
• Scheid JL, De Souza MJ. Menstrual irregularities and energy deficiency in physically active women: the role of ghrelin, PYY and adipocytokines. Med Sport Sci. 2010;55:82-102.
• Schtscherbyna A, Barreto T, de Oliveira FP; Luiz RR, de Abreu Soares RR, Gonçalves Ribeiro B. Age of onset training but not body composition is crucial in menstrual dysfunction in adolescent competitive swimmers. Rev Bras Med Esport. May/June 2012; 18(3).
• Steinberg SE, Nasraway S, Peterson L. Reversal of severe serous atrophy of the bone marrow in anorexia nervosa. JPEN J Parenter Enteral Nutr. 1987 Jul-Aug;11(4):422-3.
• Skarda ST, Burge MR. Prospective evaluation of risk factors for exercise-induced hypogonadism in male runners. West J Med. 1998 Jul;169(1):9-12.
• Sundgot-Borgen J. [Physical activity and reproductive health]. Tidsskr Nor Laegeforen. 2000 Nov 20;120(28):3447-51.
• Teufel M, Zipfel S, Herpertz S, Zwaan M. (ed.). Handbuch Essstörungen und Adipositas. Springer Berlin Heidelberg. 2008. 
• Williams NI, Helmreich DL, Parfitt DB, Caston-Balderrama A, Cameron JL. Evidence for a causal role of low energy availability in the induction of menstrual cycle disturbances during strenuous exercise training. J Clin Endocrinol Metab. 2001 Nov;86(11):5184-93.
• Wölfing B, Neumeier M, Buechler C, Aslanidis C, Schölmerich J, Schäffler A. Interfering effects of insulin, growth hormone and glucose on adipokine secretion. Exp Clin Endocrinol Diabetes. 2008 Jan;116(1):47-52.
• Yamanaka A, Beuckmann CT, Willie JT, Hara J, Tsujino N, Mieda M, Tominaga M, Yagami K, Sugiyama F, Goto K, Yanagisawa M, Sakurai T. Hypothalamic orexin neurons regulate arousal according to energy balance in mice. Neuron. 2003 Jun 5;38(5):701-13.

Carbs Past 6PM Reloaded: Circadian Shifts in Leptin and Ghrelin + Rising Adiponectin During the "Carb-Fast" Could Explain the Efficacy of Eating All Carbohydrates at Night

Image 1: Paul Bart (Kevin James) in Mall Cop (Columbia) probably would be better off weight- and health- wise without his Segway, which is by the way among the "50 Worst Gadgets of the Decade" in the Business Insider hall of shame from 2009 (Barret, Brian. 2009)

The SuppVersity was the first place you read about the how "Carbs past 6pm Will Make You Lean" (at least about the non-anecdotal scientific evidence) and for 99% of you, this will probably be the first time you read about the "follow up paper" on the original study, which was originally intended to induce a shift in the circadian pattern of leptin secretion in order to make use of its fat burning effects over night. Exactly this is the focus of a follow up paper that's soon going to be published in Nutrition, Metabolism & Cardiovascular Diseases (Sofer. 2012).

Israeli Police Diet Acadamy Reloaded!

Now the bad news is that the news are only partly new. In other words, the Israeli scientists only reevaluated the original data which was based on 63 overweight police officers who finished the original "don't eat carbs before dinner study."

And if that was not already enough, the complete hormonal profiles which had been collected on days 0, 7, 90 and 180 of the study period were only available for 39 of them.

Figure 1: 24h leptin profile before and after the intervention in the control (left) and experimental (right) group
(graph adapted from Sofer. 2012)

Still, the data in figure 1 does support the original hypothesis that the mechanism due to which the participant on the experimental diets (composition see figure 3 in "Carbohydrates Past 6PM Will Make You ... Lean!") lost ~2% more weight, and ~4% more body fat was in fact a shift in the circadian expression of leptin:

I suggest you go back to the original "Carbs past 6pm Will Make You Lean" post to read up on the details; unless you're a longstanding reader and this reminder is enough for you.

"On day 0 both groups demonstrated typical concave diurnal leptin curves, including a fall throughout the hours of 08:00-16:00, reaching a nadir at the afternoon and a rise from 16:00. On day 180, leptin curves were lower compared to day 0 in both groups. In the experimental group, the curve became more convex with a nadir only in the evening and not in the afternoon (figure 1, right). A significant difference was observed within the experimental group between day 0 and day 180 in the morning and in the evening (p = 0.023 and p = 0.021, respectively). For subjects in the experimental group that had complete data, the change in evening measurements from day 0 to day 180 was significant (p = 0.024). Using these data, the change in evening measurements was significantly greater than the afternoon and the noon change (p = 0.009 and p = 0.014, respectively). In the control group, a significant difference was observed between day 0 and day 180 at noon (p = 0.042). This result was also found for subjects with complete data (p = 0.045)." (Sofer. 2012)

What's also noteworthy is that the sparse information the scientists had on the ghrelin levels of their participants (believe it or not, but the nurse or whoever took the blood samples must have messed up, so that much of the data was lost) would suggests that the "post 6pm group" (=experimental group) were freaking hungry in the evening (see figure 1, right), but this was not the case, contrary to the subjects in the control group which had carbs from AM to PM, they did rather expose an "enhanced daytime satiety" an observation based on which Sofer et al. rigthly state that

"[...] the alteration in ghrelin’s peak from daylight hours to the evening just before dinner was another cause for the elevated daylight hour satiety, improved persistence in the weight loss process and better anthropometric outcomes that were reported [16]." (Sofer. 2012)

Next to with the circadian shifts in leptin and ghrelin levels, the pronounced increase in adiponectin (see figure 2), a reliable marker for an improved glucose tolerance, the "carb binges" which as you will probably remember included desserts such as ice-cream and co (see figure 3 in "Carbohydrates Past 6PM Will Make You ... Lean!"), probably is the third pillar of the superiority of the past-6PM carb regimen over the conventional "eat small amounts of carbs all day" approach  the control group was following.

Figure 1: 24h Adiponectin profile before and after the intervention in the control (left) and experimental (right) group
(graph adapted from Sofer. 2012)

In conjunction those three made the "impossible possible": Eat all instead of no carbs past 6PM and lose weight! Now the unfortunate truth is that this works well for people with compromised insulin sensitivity and anywhere between 15-20% body fat to shed before they approach the level of leanness (<20%) most of you probably started out with, whether it will work similarly well for significantly leaner, physically active individuals, on the other hand, remains to be seen.

Video 1: I don't want to be a spoil, but the weight loss program of the Stadtwerke Cologne which works by simply skipping dinner (!) and without any caloric restriction got some series attention here in Germany. Why? Well, it simply works... so what does this tell you? Maybe it's more about helping AMPK come to it's own, instead of stuffing yourself with readily available energy 24/7, than about exact timing or meticulously calculating macro compositions?
(click here to watch Quarks & Co.)

Bottom line: Irrespective of my all doubts about the applicability of the very same diet principle in a context, where the goal is to get really ripped and not simply non-obese, the study at hand (and I am referring to the whole experiment, here not just the last paper) does confirm that there is more to dietary success than calories in vs. calories out that having breakfast like a king is not a necessity (nuts + coffee, which was the standard breakfast in the experimental group, or nothing, which is Adelfo Cerame's standard breakfast, work just as well) and that the influence of circadian rhythms goes far beyond our sleep-cycles... which reminds me that I'll do my very best to get into more details on that in the coming episode III of the SuppVersity Circadian Rhythm Series on Sunday. Until then, try not to lose the beat ;-)

References:

• Barret, Brian. The 50 Worst Gadgets Of The Decade. Business Insider. Dec 31, 2009. < http://www.businessinsider.com/the-50-worst-gadgets-of-the-decade-2009-12?op=1 > retrieved on Aug 24, 2012.
• Sofer S, Eliraz A, Kaplan S, Voet H, Fink G, Kima T, Madar Z. Changes in daily leptin, ghrelin and adiponectin profiles following a diet with carbohydrates eaten at dinner in obese subjects. Nutr Metab Cardiovasc Dis. 2012 Aug 14.

On Short Notice: Ghrelin & GH Boosting Fats for Intermittent Fasting, 4-AD, 5-AA, Testosterone & Co in "Pod", Too Much Vitamin D for Your Prostate, Estrogens in Milk & More

Image 1 (fidged-group.co.uk): Being average may not be sexy, but one thing I did not mention in the summary of what you are going to learn today is that an average amount of body fat (not the new average American though ;-) could hold the key for a longer life - ah, I almost forgot: This is only valid if it comes with an appropriate amount of lean mass, which is still the best predictor of a long and healthy life!

Somehow these On Short Notice posts become increasingly longer... I had to "outsource" a couple of items, to reduce today's installment to a manageable length, but don't worry a couple of them will turn up in the next installment or make it into the regular news in the days to come. For now you will have to settle for valuable and at least in part surprising insights into the broad range of effects different types and loads of dietary fat can have on your appetite, metabolism and your, or rather your bacterial subtenants' methane production. You will also learn what TAC means and why you want more than 1,080 units of it in every 100g of whatever you are stuffing down your pie-hole. You will be surprised to hear that SuppVersity student FatFree instinctively chose the low estrogen variety of dairy, when he "downed 1l of raw goat's milk" from his local farmer earlier today (see respective comment) and you will attend another lesson of the "what's good for your obese neighbor, is not necessarily good for you" class. All that will be topped of with some testosterone laden, WADA prohibited "pod", too much vitamin D for your prostate to handle and a glass of bone-conserving wine for the habitual drinkers among the ladies ;-)

Fat Interactions - MUFA, PUFA, SUFA and How They Influence Your Metabolism

The idea that "not all fats" are created equal is meanwhile broadly accepted. What is still a matter of constant debate, though, is which of the three main classes, i.e. saturated, mono- and polyunsaturated fatty acids exert beneficial and which of them detrimental effects on our health. A recently published on the differential effects of butter (saturated fat), olive oil (mono-unsaturated; oleic acid + a relative high amount of omega-6), fish oil (polyunsaturated; high omega-3) and soybean oil (polyunsaturated; mainly omega-6 + some omega 3) on the expression of the purported "hunger hormone" ghrelin (note: acetylghrelin, which was measured in this study, is the "active" variety of ghrelin) may yet help to get a better grasp of what exactly we should be looking for (Saidpour. 2012), when it comes to the downstream metabolic effects of high amounts of certain fatty acids - and no, it is not for maximal ghrelin suppression.

Figure 1: Food intake (in g, left), body weight (relative to control group on regular diet, middle) and acetylghrelin levels in the fasting and fed state during the 8-week experimental period (data based on Saidpour. 2012)

As the data data in figure 1 shows, the 5-week old male Wistar rats who had been randomly assigned to either standard rodent chow or calorically identical (3.98kcal/g of food) high fat diets who were fed ad libitum every other day only to maximize the ghrelin response) for 8 weeks did not, as common sense would suggest, eat the least and gain the least on the saturated fat (butter) diet with its long lasting satiety effect (as evidenced by the lowest fasting ghrelin levels).

In fact, the exact opposite was the case: The acute satiety effect of the fish oil and olive oil diets (as evidenced by the plummeting acetylghrelin levels in the fed state) turned out to be the main determinant of the amount of food the rodents, who were effectively intermittently fasted (though with a pretty long fasting window of 24h), consumed.  And while the low ghrelin levels in the fed state reduced the food intake, the fasting induced rise of acetylghrelin to 23% higher levels than in the butter fed animals has probably given them the metabolic advantage of elevated growth hormone levels. At least this is what we must expect based on the ability of ghrelin to directly bind to the GHS receptor and induce the release of the fat annihilating 191-amino acid, single-chain polypeptide from the lateral wings of the anterior pituitary gland (Kojima. 1999).

Bottom line: While this is certainly only another small piece to the oftentimes puzzling effects of fatty acids (check the "On Very Short Notice" items in this installment for more "puzzling" effects ;-), it does not only provide another mechanism by which the original "Mediterranean diet", which is rich in both fish and olive oil and by no means as fat free as its latest mainstream interpretation would suggest, could in fact provide a metabolic edge. And though the "intermittent fasting" feeding pattern may reduce the significance of the results for the "average" inhabitant of the Western hemisphere, who can hardly go 2h without a Snickers bar or at least a sugar-laden coffee, it does suggest that all the "lean gainers" and "intermittent fasters" out there could derive great benefits from a huge piece of salmon and couple of tablespoons of high MUFA olive, macadamia or artichoke oil in their "feeding windows".

A Diet High in Dietary Antioxidant Keeps you Lean & Healthy

Image 2: Clover is among the most potent antioxidant foods.

You know that I am very critical when it comes to the supply of exogenous antioxidants (cf. "Multivitamins, a question of Faith?!"; more on multivatmins), but would never even remotely consider limiting the supply of whole foods that are rich in antioxidants. I was thus not very surprised, when I read that the consumption of high amounts of dietary antioxidants was associated with statistically significant lower body weight and abdominal fat gain in a 3-year longitudinal (this is where scientists analyze data from the same persons on different time-points) study from the University of Medical Sciences in Teheran (Bahadoran. 2012).

Foods	TAC
Cloves (see image), Cinnamon, Oregano, Tumeric, Acai (all dried or grounded)	300,000 -100,000
Cacao, Parsley, Basil, Currry, Sage, Peppercorns, Mustard, Ginger, Marjoram	100,000 -25,000
Rice bran, Chili, Pecans, Paprika, Choke berries, Elderberries, Kidney Beans (dried), Oregano, Walnuts	25,000 -10,000
Hazelnuts, Cranberries, Artichoke hearts, Blueberries, Prunes, Pistachios, Blackcurrant, Artichokes, Plums, Blueberries (cult.) Lemon balm (fresh) Blackberries, Garlic, Coriander,	10,000 -5,000
Raspberries, Basil (fresh), Almonds, Apples, Dates, Strawberries, Figs, Peanuts, Raisins, Cherries, Asparagus, Spinach	5,000 -2,500
Cornflakes, Red Cabbage, Gooseberries, Cashews Avocado, Pears, Peaches, Oranges, Oats, Macadamia, Tangerines, Broccoli, Potatoes, Grapefruit, Red grapes	2,500 -1,500
Carrots, Olive oil, Green grapes, Mango, Lettuce, Radish Eggplant, Kiwi, Banana, Red pepper, Pineapple, Artichoke, Nectarines, Pine nuts, Cauliflower, celery	1,250 -500
Leeks, Lettuce, Baby carrots, Tomatoes, White wine, cantaloupe, Honeydew, Watermelon, Cucumber	500 -100

In particular, Zarah Bahadoran and her colleagues found that the consumption of foods with an average total antioxidant capacity equal to 1,080µmol TAC essay units per 100g - something your would get from oats + blueberries or a handful of pecans and an apple - was associated with a -38 % decrease in the risk of central obesity (note: The TAC essay is an experimental measure of the total antioxidant capacity of food and is independent of whether it's phenols, vitamins, thiols or whatever that contribute to the antioxidant effects of a food; the clear disadvantage of this method is that it does not really tell you what exactly the compounds will do outside of a petri dish, but, but this is the topic for another blogpost ;-)

And while some of the confounding factors have been eliminated from the above hazard risk calculations, it is still worth to take note of the fact that...

• people with the highest antioxidant intake consumed food with the lowest energy density (so they cannot be eating nuts and chocolate only ;-)
• women consumed significantly more antioxidants than men, with +10% more women in Q3 (959-1080µmolTE/100g) and +15% more women in the critical Q4 (>1,080µmol/kg) quartiles
• the more leisure time the subjects had, or I should say allowed themselves, the higher was their antioxidant intake
• high antioxidant consumers were also dairy lovers with 81% more dairy consumption in the highest quartile, exactly those people, thus, who consumed the >1,082 µmolTE/100mg diets
• needless to say that people who are reckless enough to smoke also consumed the least antioxidants

Aside from these significant differences, the non-existence of other differences people often take for granted, such as the notion that education and job activity, or different macronutrient compositions would have an impact on the total amount of antioxidants you consume, is certainly worth mentioning.

  On Very Short Notice

• 

  Figure 2: "Pod" contains a hell lot of steroids. Unfortunately, most of them will be dumped by right into the urine specimen for the WADA agents (data based on Thevis. 2012)

  "Pod" doping could get you banned, but probably won't increase your performance - While I cannot tell you what the swimmers at the Olympics have been taking to break world record after world record (some even in consecutive races on the same day), I can tell you that it were not the reddish-brown musk grains from the dried secretion from the preputial follicles of the male musk deer , which are located in the "pod", a small sac in close proximity to the preputial orifice (see figure XYZ, upper right), because none of these athletes would have passed the WADA doping controls had he or she taken a couple of grams of those steroid-containing staples of Traditional Chinese Medicine.
  Now, despite the fact that we do see "classics" such as 4-AD, Androsterone, Epiandrosterone, DHEA and even minuscule amounts of the "Big T" (1-6µg/g with the highest level in the pod from the zoo animals from Leipzig, Germany - read more about testosterone's ability to build muscle in the "Intermittent Thoughts on Building Muscle") testosterone , the total amount of those compounds which could actually induce noticeable performance increases may be high enough to show up during doping controls as the five cases during the last FIFA Women World Cup show(cf. Thevis. 2012), it does not appear reasonable to assume that the rumored performance enhancing effects of musk (pod) extracts would stand the test in a placebo controlled supplementation trial.

• 

  Figure 3: When administered at a HED of ~750mg/day sodium salicates reduce the glucose (left axis) and insulin (right axis) levels in response to a standardized intraperitoneal glucose injection in obese mice, they do the opposite in lean mice (based on Nixon. 2012).

  Salicates block cortisol expression in fat cells and increase insulin sensitivity in obese mice, but... as we have seen for alpha lipoic acid (see "ALA? You are Better of Without the Purported Nutrient Repartitioner") and tons of other "wonder-supplements", things that are good for your obese neighbor will rarely work out for lean folks like, yourself; and thus it should not come as a surprise that the blockade of adipose tissue 11-beta-HSD, the enzyme that converts cortisone, the inactive form of cortisol into it's active twin, exerts no, if not the exact opposite effect (see figure 3; adapted from Nixon. 2012).
  So, if you are lean and want to stay lean, leave the aspirin, the 7-ketos and other overpriced 11-beta-HSD inhibitors or "cortisol blockers" to those who need them - inflamed, overweight (pre-)diabetics.
• Purportedly anti-carcinogenic high vitamin D levels increase risk of prostate cancer - Swedish scientists found a statistically significant trend towards an increased risk of developing prostate cancer with rising vitamin D levels. In the 7th and 8th decile which corresponds to plasma vitamin D levels of 91-97 nmol/L the calculated risk of developing prostate cancer was 67% higher than in the lowest decile (Brändstedt. 2012). Other than previous studies which reported associations between high calcium intake and prostate cancer risk, Brändstedt et al. observed an association between high serum calcium levels and prostate cancer levels only among men aged 55-65 who had a BMI < 25. It is thus very unlikely that the underlying reason of the pro-carcinogenic effects was an increase in calcium absorption... hmm, I don't have to remind you of (a) the antagonism between vitamin D and vitamin A and (b) last weeks news on the anti-carcinogenic effects of the latter, do I?

• 

  Image 3: Although the scientists controlled the compliance by measuring the serum concentration of fatty acids instead of using unreliable food logs, there are still  a lot of uncontrolled confounding variable, here. Hower, the same can be said of those studies on which the concept of the pro-inflammatory omega-6s is based. Anyway, I will still eat butter, not margarine and if olive oil is one of staple sources of dietary fat, you will be getting plenty of omega-6 from this purported GH booster (see previous new item)

  High omega-6 diet reduces insulin, total/HDL-cholesterol ratio, LDL cholesterol, and triglycerides - Helena Bjermo and her colleagues from the Uppsala University in Sweden report that feeding 67 abdominally obese patients (15% were diabetic) either a butter-based high saturated fat diet or a diet that was particularly rich in linoleic acid (omega-6 mainly from sunflower oil; 15% of the total energy intake) for 10 weeks had very differnt effects on the hepatic fat content an other highly relevant markers of metabolic health. Despite the fact that both diets were isocaloric, the butter-based high saturated fat diet increased the hepatic fat content of the study participants (measured by MRS) by 10% while the subjects in the high PUFA group were able to reduce the fat content of their livers by -35%. Similarly, the basal insulin level, triglycerides, as well as total and LDL cholesterol increased in the butter eaters and decrease or remained the same in the 15% linoleic acid group.
  The results are honestly not what I had expected, but in essence only further evidence there is still a lot to learn about the shades of grey that exist between the dichotomous black and white that is still so characteristic of the way we think about fats.
• Goat's milk is the better choice for people concerned with limiting their intake of exogenous estrogens - According to analyses that were conducted at the Laboratory of Proteomics and Analytical Technologies in Frederick (Farlow. 2012), cow's milk contains significantly more estrogens (estrone and 17beta-estradiol) than goat's milk and that irrespective of whether it was organically produced or not. Bad news for the reproductive health of the North Americans and Europeans, where the consumption of cow's milk exceed that of goats milk by several magnitudes and good news for the fertility of the rest of the world, where goat's milk still is the "milk of choice".

• 

  Image 4: Looks like this was not the only potential side effect of methane producing bacteria in your gut.

  High fat diets increase the ratio of methane producing to other bacteria and thus increase obesity risk - Most of you will probably remember the finding that mice without gut microbiome are more or less resistant to dietary induced obesity. A recent study does now suggest that (as it was to be expected) not all bacteria are created evil.. ah, pardon... equal ;-) In the lab mice of Ruchi Mathur and his colleagues, the tendency to develop obesity correlated with the amount of gastrointestinal (GI) methanogens, including Methanobrevibacter smithii, and was independent of the presence of other bacteria (Mathur. 2012).
  With the pro-methanogenic (=allows those little bastards to grow) effects of high fat diets Mathur et al. may in fact have found another potential co-founder in the development of the metabolic syndrome. Interestingly enough Methanobrevibacter smithii is also the predominant methanogen in patients with constipation-dominant IBS and methane breath (Kim. 2012) - so if that is you, this could be one of the few cases where the use of a broadband antibiotic could save you from a lot of ailments, because you would thus not have to care about contradictory results from Million et al., as well as dozens of other studies, each of which identifies another type of bacteria as 'the root cause' of the obesity epidemic - in Million's case the name of the scapegoat is Lactobacillus reuteri, by the way (Million. 2012).
• Mediocrity guarantees a long life - At least when it comes to body fatness being too lean and being too fat are equally detrimental to the life expectancy of male 65+ agers (Toss. 2012). If you are women, though, the results Fredrik Toss and his colleagues published in the latest issue of Age and Ageing suggest that being on the chubbier side of things can actually be life-saving, as long as you carry the fat in the gynoid and not the abdominal area. Most importantly, however, lean mass, or as my buddy Carl Lanore calls it, "metabolic currency" is yet still the most significant predictor of survival in older subjects - in other words: Don't even think of emulating the skinny fat celebrities with their starvation diets and endless cardio sessions if you intend to live your grand- and grand-grand-children, better check out yesterday's news on the "Iranian HIIT Solution for Improved Insulin and Leptin Sensitivity".

• 

  Image 5: If you are concerned about bone health, menopause is not the best time to stop drinking... unless you start weight lifting, of course ;-)

  Don't stop drinking alcohol in menopause! At least if you don't want to increase bone-resorption, i.e. the leeching of calcium from your bones. This is the surprising result of a recently published study by Jill A. Marrone and colleagues, who had  investigated the effects of total abstinence from alcohol in 40 healthy postmenopausal women (mean ± SE age, 56.3 ± 0.5 y) who consumed the alcohol equivalent of ~1 glass of wine per day (Marrone. 2012). Interestingly, the bone formation marker osteocalcin and the resorption marker C-terminal telopeptide (CTx) returned to their normal values, once the women resumed their former drinking habits.
  In view of the fact that there was also a significant correlation between baseline bone-density, as measured dual-energy x-ray absorptiometry, and the extent of mild to moderate alcohol consumption, these results raise the question whether "bone health" would be another factor to add to the list of the "minimalist approach" to alcohol consumption.

References:

• Bjermo H, Iggman D, Kullberg J, Dahlman I, Johansson L, Persson L, Berglund J, Pulkki K, Basu S, Uusitupa M, Rudling M, Arner P, Cederholm T, Ahlström H, Risérus U. Effects of n-6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial. Am J Clin Nutr. 2012 May;95(5):1003-12. 
• Brändstedt J, Almquist M, Manjer J, Malm J. Vitamin D, PTH, and calcium and the risk of prostate cancer: a prospective nested case-control study. Cancer Causes Control. 2012 Aug;23(8):1377-85.
• Farlow DW, Xu X, Veenstra TD. Comparison of estrone and 17β-estradiol levels in commercial goat and cow milk. J Dairy Sci. 2012 Apr;95(4):1699-708.
• Kojima, M., Hosoda, H., Date, Y., Nakazato, M., Matsuo, H., Kangawa, K. Ghrelin is a growth hormone releasing acylated peptide from stomach. Nature. 1999; 402, 656-660.
• Mathur R, Kim G, Morales W, Sung J, Rooks E, Pokkunuri V, Weitsman S, Barlow GM, Chang C, Pimentel M. Intestinal Methanobrevibacter smithii but Not Total Bacteria Is Related to Diet-Induced Weight Gain in Rats. Obesity (Silver Spring). 2012 Jun 7. 
• Marrone JA, Maddalozzo GF, Branscum AJ, Hardin K, Cialdella-Kam L, Philbrick KA, Breggia AC, Rosen CJ, Turner RT, Iwaniec UT. Moderate alcohol intake lowers biochemical markers of bone turnover in postmenopausal women. Menopause. 2012 Jul 9.
• Million M, Maraninchi M, Henry M, Armougom F, Richet H, Carrieri P, Valero R, Raccah D, Vialettes B, Raoult D. Obesity-associated gut microbiota is enriched in Lactobacillus reuteri and depleted in Bifidobacterium animalis and Methanobrevibacter smithii. Int J Obes (Lond). 2012 Jun;36(6):817-25.
• Nixon M, Wake DJ, Livingstone DE, Stimson RH, Esteves CL, Seckl JR, Chapman KE, Andrew R, Walker BR. Salicylate downregulates 11β-HSD1 expression in adipose tissue in obese mice and in humans, mediating insulin sensitization. Diabetes. 2012 Apr;61(4):790-6.
• Saidpour A, Kimiagar M, Zahediasl S, Ghasemi A, Vafa M, Abadi A, Daneshpour M, Zarkesh M. The modifying effects of fish oil on fasting ghrelin mRNA expression in weaned rats. Gene. 2012 Jul 25.
• Thevis M, Schänzer W, Geyer H, Thieme D, Grosse J, Rautenberg C, Flenker U, Beuck S, Thomas A, Holland R, Dvorak J. Traditional Chinese medicine and sports drug testing: identification of natural steroid administration in doping control urine samples resulting from musk (pod) extracts. Br J Sports Med. 2012 May 6.
• Toss F, Wiklund P, Nordström P, Nordström A. Body composition and mortality risk in later life. Age Ageing. 2012 Jul 20.