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.

---

Have you ever listened to the to the SuppVersity Science Round Up on Super Human Radio? If not, check out the podcasts

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.