Weight Loss Program for Health: healthy aging

Showing posts with label healthy aging. Show all posts

Physical & Cognitive Exercise Are Similarly Effective DNA Protectors & Antioxidant Boosters in Elderly Men & Women

Brain builders and muscle builders are similarly effective DNA protectors in the elderly.

As a SuppVersity reader you won't be surprised to hear that Bernhard Franzke and his colleagues from the University of Vienna were able to confirm that resistance training can improve the resistance of human DNA to H2O2 damage in institutionalised elderly. What may be news to you, though, is that very similar effects can be achieved by cognitive training in form of coordinative or cognitive tasks that were performed only two times per week by the 105 institutionalised elderly women and men (aged 65–98 years) the scientists recruited from five different senior residences in the area of Vienna (Franzke. 2014).

DNA damage is obviously important, maintaining optimal lean mass levels is important, too

Tri- or Multi-Set Training for Body Recomp.?

Alternating Squat & Blood Pressure - Productive?

Pre-Exhaustion Exhausts Your Growth Potential

Full ROM ➯ Full Gains - Form Counts!

Battle the Rope to Get Ripped & Strong

Study Indicates Cut the Volume Make the Gains!

In the recent Austrian study, the subjects had been randomized to three groups. The previously described cognitive training group, which also served as a "control", as well as two resistance training groups.

"The RT groups (RT and RTS) performed two sessions of RT per week, supervised by a sport scientist, conducted on two non-consecutive days. Training attendance was recorded every session. The only equipment used was exercise bands and a chair. [...] The main part consisted of 10 exercises for the main muscle groups (legs, back, abdomen, chest, shoulder and arms). One training session started with 10 min of warm-up, continued with 30–40 min of strength training and ended with a 10-min cool-down. To keep the training stimulus high enough, the exercise program was adjusted to the participants’ individual needs, by either adapting the resistance of the elastic band (shorter or stronger band) or by modifying the exercise, by means of performing a more diffiult version. In the initial phase (4 weeks) one set of 15 repetitions was performed in order to learn the correct form of each exercise. From the fifth week on, the intensity and volume were progressively increased from two sets of light exercises to two sets of heavy resistance. If the participants could easily perform two sets of 15 repetitions they were told either to take more resistance or to perform a more difficult version of the exercise" (Franzke. 2014).

In contrast to the RT group, which did "nothing", but the previously described resistance training regimen, the subjects in the RTS group consumed a multi-ingredient supplement every morning, as well as directly after each training session. Said supplement consisted of 20.7g protein [56 energy (En) %, 19.7g whey protein, 3 g leucine, >10 g essential amino acids], 9.3 g carbohydrates (25 En%, 0.8 BE); 3.0 g fat (18 En%), 1.2 g roughage (2 En%), 800 IU (20 μg) of vitamin D, 250 mg calcium, vitamins C, E, B6 and B12, folic acid and magnesium (one portion FortiFit, Nutricia with a total energy content per drink of only 150 kcal).

Figure 1: Changes in parameters of DNA damage and antioxidant enzyme expression (Franzke. 2014).

In spite of the fact that the intake of the nutritional supplement was controlled at breakfast as well as after the training sessions, it did not provide significant additional benefits on top of the regular resistance training protocol.

We should keep in mind, though, that (a) non-significant benefits were visible for the formamidopyrimidine DNA glycosylase (FPG) and the expression of superoxide dismutase and that (b) the actual benefits of protein supplements would have become visible only if the scientists had accessed the changes in body composition, as well.

Maximal protein synthesis - How much protein do the elderly need? Find out in a previous SV article.

Bottom line: If you don't have a present for your grandpa or grandma, yet, I suggest you craft a voucher for 2 weekly resistance training and cognitive training sessions with yourself as a trainer and buy a tub of protein to round your present off...

All Christmas jokes aside, the study at hand simply confirms what the proverb "a rolling stone gathers no moss" implies. Exercise, no matter whether it's cognitive or physical exercise, protects aging men and women from pro-cancerous DNA damage and ensures that can maintain "a sound mind in a sane body" | Comment on Facebook!

References:

Franzke, B. et al. "The impact of six months strength training, nutritional supplementation or cognitive training on DNA damage in institutionalised elderly." Mutagenesis (2015):147–153.

Stretch-Shortening Cycle Exercise Superior to Eccentric Exercises in the Elderly - Identical Size & Strength Gains, With a Functional Advantage for Stretch Shortening Ex.

A stretch-shortening cycle (SSC) is an active stretch (eccentric contraction) of a muscle followed by an immediate shortening (concentric contraction) of that same muscle - e.g. jump squats.

Sacropenia, i.e. the age-related loss of muscle mass is a huge problem in our society. A problem the consequences of which start to surface way before older men and women suffer from serious limitations in their mobility and their ability to master (no longer) ordinary everyday-life tasks.

The loss of muscle mass is after all associated with an ever-increasing risk of metabolic syndrome, i.e. obesity, diabetes, high blood lipids, etc. (Baumgartner. 2004; Kim. 2011) - in both, young and old individuals, as well.

In contrast to many pharma-funded which spends millions of dollar on "promising new drugs" (that's what they say) to solve the problem.

Learn more about building muscle at www.suppversity.com

Tri- or Multi-Set Training for Body Recomp.?

Alternating Squat & Blood Pressure - Productive?

Pre-Exhaustion Exhausts Your Growth Potential

Exercise not Intensity Variation for Max. Gains

Battle the Rope to Get Ripped & Strong

Study Indicates Cut the Volume Make the Gains!

Researchers like Márk Váczi and his colleagues from the University of Pécs have long recognized that the development "promising new drugs" holds much less promise that the optimization of exercise regimen that are targeted to prevent sacropenia. In their latest paper in Experimental Gerontology the researchers describe the results of an experiment that was conducted to compare the effects of exercise training using stretch-shortening (SSC) and eccentric contractions (ECC) on the mechanical function and size of the quadriceps muscle and hormonal adaptations in healthy old males (N=16; age: 60-70 year old).

Figure 1: The torque–time curves of a stretch-shortening cycle and an eccentric exercise training contraction highlight the main difference between SSC (short, ultra-intense) and ECC (long, medium intensity) knee extensions (Váczi. 2014)

In that, Vávzi et al used an experimental approach in which the total mechanical work was identical in the two training groups and hypothesized that mechanical, hormonal, and muscular adaptations would differ in response to SSC vs. ECC exercise (note: plyometric training harnesses the beneficial effects of SSC | learn more).

The exercise of choice was, as so often, the single-lateral knee extension. The subjects trained 2-3 times per week with 48h rest between two sessions (each between 9-11 am in the morning).

Benefit from SSC irrespective of your age after you've read the following SuppVersity Classic: "Building the Jack-of-All-Traits Legs Workout With Squats, Jump Squats and Body Weight Plyometrics? At Least for Physical Education Students that Seems to Work." | read more
"Subjects performed 4 sets of 8 to 14 repetitions of unilateral knee extensions with both legs, with 2 min of rest between sets. The exercising legs were alternated across sets. The training contractions in SSC and ECC groups were similar to the SSC and ECC test contractions. [...A] unique element of the training program was that the average mechanical work for a session was still similar in the two groups. This was achieved by manipulating the stretch-load in the SSC group. For example, if a subject in the ECC group improved mechanical work production due to adaptation to the training, the stretch-load was adjusted to match subject-pair's mechanical work in the SSC group." (Váczi. 2014)

If we take a look at the outcome of the work and volume matched training with stretch-shortening and eccentric leg extensions, we see the following differences and similarities, when comparing the two exercise regimen:

Figure 2: The hormonal response to the exercise regimen was more or less identical (Váczi. 2014)
There was a significant group by period interaction for RTD30 [rate of torque development after 30ms] and RTD50 (p < 0.05), suggesting that the two groups responded differently to the training.
There was no group by period by time interaction in any of the hormonal variables, suggesting similar re sponses to the two training regimens. There was a significant time main effect in testosterone (p = 0.010), suggesting that the two exercise bouts (before and after 10 weeks training) uniformly increased testosterone 15% from pre to IP, and then decreased 10% from IP to 5 min post-exercise.
There was a time main effect for cortisol (p = 0.018), suggesting that the two exercise bouts uniformly increased cortisol 21% from pre to IP, and then further increased 6% to 5 min post-exercise.
There was a time main effect for testosterone/cortisol ratio (p = 0.002), suggesting that the two exercise bouts uniformly decreased the ratio 17% from pre to 5 min post-exercise.

Now, in view of the fact that the overall strength (MCV) and size gains (CSA) were identical, as well. It would seem as if both types of exercise were equally beneficial.

Figure 3: Changes in maximum voluntary contraction (MVC), rate of torque development after 30ms and 50ms and cross sectional area of the quadriceps muscle (CSA) after 10 weeks of training (Váczi. 2014)

If we look at the most important functional deficits in aging muscle, however, it becomes obvious that the ostensibly negligible increase in the rate of torque development at the beginning of the exercise could determine whether an older individual falls and breaks a bone or whether he or she manages to "catch him-/herself" in time.

Bottom line: Overall the study at hand underlines there is more than just one way to skin the cat. In that, small allegedly practically non-significant differences like the increased rate of torque development in the study at hand can - from time to time - have important real-world relevance.

Figure 4: Strength & size gains in young men in response to 8 wk of SSC exercise training

And even if you are not 60 years and older, you can benefits. In 2005, Malisoux et al. evaluated the contractile properties of chemically skinned single muscle fibers from the leg muscle of eight young men before and after 8 wk of maximal effort stretch-shortening cycle (SSC) exercise training and found that their maximal leg extensor muscle force, vertical jump performance and peak force were improved 12%, 13% and 15-19% (depending on muscle fiber type), respectively; and the single-fiber crosssectional area increased 23% in type I, 22% in type IIa, and 30% in the most growth prone type IIa/IIx fibers. Needless to say that this makes SSC exercises "an effective training approach to improve fiber force, contraction velocity, and therefore power." (Malisoux. 2005) | Comment on Facebook!

References:

Baumgartner, Richard N., et al. "Sarcopenic obesity predicts instrumental activities of daily living disability in the elderly." Obesity research 12.12 (2004): 1995-2004.
Kim, Tae Nyun, et al. "Skeletal muscle mass to visceral fat area ratio is associated with metabolic syndrome and arterial stiffness: the Korean Sarcopenic Obesity Study (KSOS)." Diabetes research and clinical practice 93.2 (2011): 285-291.
Malisoux, Laurent, et al. "Stretch-shortening cycle exercises: an effective training paradigm to enhance power output of human single muscle fibers." Journal of Applied Physiology 100.3 (2006): 771-779.

Science Round-Up Seconds: Are Statins Good for Your Brain? Or Have the Scientists Just Forgotten About the Risks?

Brainy question of the day: Will statins revive or criple your brain?

Those of you who made it in time for yesterday's live-show, will already know that I have "postponed" publishing the (by then) commented list of dietary supplements to improve and maintain insulin sensitivity to Sunday.

It was my original plan to publish this list along with three suggested supplement stacks on Sunday and sticking to it has the advantage of a "true" ending to the "Maintain and Improve Your Insulin Sensitivity" series (read previous posts) - there is already enough chaos among the 1351 published SuppVersity posts ;-).

Furthermore, it will unquestionable be good for your brain, if I do not flood it with an informational overload by trying to cram all the information about the insulin sensitizers, as well ;-)
I have to admit that I must have over-read the original article a listener who goes by the name "Rad Fox" referenced in an email he send to onair@superhumanradio.com (feel free to bother us with questions for future episodes). In this email "Rad" referenced an article which turned out to be one of these notorious copy + paste pieces of a press release. The latter came from John Hopkins Medicine and discussed the results of an as of now unpublished paper about the incidence of dementia in patients on statin therapy.

This is not the first review that connects statin use to brain health!

Despite their bad reputation within the health and fitness community, the use of statin drugs has in fact been shown in numerous studies to keep your brain on top of the game. Another very recent meta-analysis of data from studies with 2851 cases and 57020 participants, for example, says that statin use is associatied with a statistically significant -48% reduction in dementia risk (Song. 2013). Similarly, Steenland et al. write in a paper that's been published roughly a month ago:

"Research volunteers with normal cognition at baseline evaluated an average 4.1 times over 3.4 years (1,244 statin users, 2,363 nonusers) and with mild cognitive impairment (MCI) at baseline evaluated an average 3.9 times over 2.8 years (763 users, 917 nonusers)." (Steenland. 2013)

Irrespective of the high number of empirical studies that seem to support the efficacy of statins as "anti-dementia" drug, I did not even have to bother with PubMed or any other medical database to find trials that suggest that the use of statin drugs will have the exact opposite effects. I just had to scroll down to the end of the article, where I found a news report on an study that claims that Pravachol, obviously likewise a statin drug, would be "linked to memory impairment" (read the news story).

Beneficial or detrimental? Which results can you trust?

Your body does in fact produce i's own anti-dementia "drug": Melatonin. With the natural decline of the metlatonion production with age, it is thus only logical that you develop dementia, only in your older age - learn how to protect yourself with melatonin

I know it can be enervating at time, but it's one of the central characteristics of science that it's results are usually ambiguous and far from achieving the status of "undebatable truths". If you've been around the SuppVersity for some time now, you should by now have overcome this naive understanding of the nature of science by now, anyways.

"The promising results obtained in vivo and in epidemiological studies are generally not in accordance with those of placebo-controlled randomized clinical trials." (Silva. 2013)

You should also be aware that the best way to reconcile these discrepancies between epidemiological and experimental evidence is to identify the underlying mechanism behind the effects statins exert on the build-up of neuronal plaque. As soon as we know exactly what's happening we may well be able to decide whether the protective effects we see are "real" or just an "epidemiological Fata Morgana".

The most important question we have to answer is: "HOW?"

Unless we have a rationale explanation for the protective effects statins may have on the brain of (elderly!) individuals, we can file the claim "statins protect elderly brains against cognitive decline" in the "still to be investigated" folder and let it rest there until we have a verifiable theory (= sum of hypothesis) to explain how the use of a drug that was originally designed to block the endogenous production of cholesterol could have such an effect on the brain.

Dietary vs. endogenously produced cholesterol: I know that most of you will be aware that statins reduce your bodies own (=endogenous) production of cholesterol. Most of you will probably also know that it is this endogenously produced cholesterol that is - if any form of cholesterol - to be held responsible for coronary heart disease and (purportedly) the formation of plaque in the brain.

If you are not a narrow-minded text-book physician, you will have to acknowledge that eggs promote an anti-artherogenic cholesterol profile and will thus probably have anti-Alzheimer's and anti-dementia effects (learn more)

For the average human being, his dietary cholesterol intake will have no or only minor influence on the serum levels of cholesterol and cholesterol rich foods such as eggs, have actualle been found to exerd positive effects on the cognitive function of elderly individiuals (Aparicio. 2013); and despite the fact that the results did lose their significance, when they were stratified for total energy intake and education level, the Aparicio study should remind us that the role cholesterol rich foods do not necessarily increase your dementia risk, even if cholesterol was mechanistically involved in the etiology of dementia - even if studies in rodents and rabbits who were fed with synthetic high cholesterol diets suggest otherwise (learn more about the problems with synthetic diets).

And what about saturated fat? In a study from Japan (the Hisayama Study; cf. Ozawa. 2013), the consumption of a diet with a normal amount of saturated fat in it and not the allegedly healthier "almost zero SFA" pattern were associated with reductions in all cause (-34%), Alzheimer's (-35%) and vascular dementia (-55%) - a direct negative effect of saturated fats is thus unlikely. A negative impact of certain foods that happen to have a high amount of saturated foods in them, on the other hand, cannot be excluded.

The most straightforward explanation for the beneficial effects scientists observed in numerous epidemiological studies would obviously be a direct one: "Statins take away a substrate that's necessary for the amyloid plaque to form." This hypothesis would also be supported by significant correlations between elevated serum cholesterol levels and plaque build-up in the brain, as they were observed by (among others) by Matzusaki et al. in who used the same cohort Ozawa et al. analyzed in their study on the influence of certain dietary patterns on the risk of developing dementia (see red box above). In the corresponding paper Matzusaki et al. report:

Table 1: Official "normal" levels for total, LDL & HDL cholesterol, as well as triglycerides (based on AHA recommendations)

23x higher risk for total cholesterol > 5.8mmol/L
13x higher risk for LDL > 4.02 mmol/L
70% higher risk for HDL < 1.04 mmol/L (p > .5)
3.5x higher risk for triglycerides >1.56mmol/L
that's compared to Q1 <0.51mmol/L
7x higher risk for LDL / HDL > 3.48 mmol/L
3.1x higher risk for “non-HDL” > 4.61 mmol/L

What makes Matzusaki et al.'s observation particularly interesting is the fact that they are based on 147 autopsies that were performed between 1998 and 2003. Autopsies? Yes, I know that sounds gross and irrelevant, but it has the advantage of

being able to measure the amount of plaque directly,
having physical and quantitative data, and
not being limited to diagnosed cases of dementia.

In other words: Your data is not going to be skewed by analyzing only those who are already sick enough to be treated, when you are able to look at the brains of a representative sample of the population after they died.

Dead or alive, there is more than one hypothesis

Remember: We are inclined to forget that the only difference between "effects" and "side effects" is our assessment of the latter. The beneficial effects statins have on the expression of AGE receptors, for example would be "side effects" for a classic statin which is obviously supposed to lower cholesterol and nothing else. In the context of dementia prevention, this side effect it is the intended effect and the cholesterol lowering effects of statins are the "side effects".

In view of the myriad of already discovered and hitherto undiscovered "side effects" of statins it is however just as likely that the reduced dementia risk is a result of ...

a reduction in advanced glycation end product receptors in the brain and thus a protection against the negative effects AGEs exert on the brain (Liu. 2012; Deane. 2012).
On a side note: If you want to counter the production of endogenous AGEs you can do so with taurine (Nandhini. 2004). This would obviously render the use of a statin to reduce the receptor density obsolete.
a blockade of the “maturation” from plague precursors to amyloid beta plaque (Hosaka. 2013)

... or a combination of all these effects with the direct and indirect role cholesterol plays in the formation of plaque in the brain (Fantini. 2013; Hung. 2013).

Whether we will ever really know that it is that appears to protect statin users from dementia is thus obviously still anybody's guess. What is not "anybody's guess" is whether it makes sense to take a statin solely to protect yourself from developing dementia. That would - in my humble opinion - rather be a sign of existing cognitive decline than a protection against its development ;-)

Bottom line: Despite the fact that I have never been a statin advocate it is difficult to argue with the current epidemiological evidence: People who take statins have a lower incidence of dementi *fullstop* Whether this is even related to cholesterol is however as questionable as Carl's suggestion that it's an overall reduction in inflammation as it has been observed by Reis et al. (2012) in the context of Malaria infections, where statins appear to be able to sooth the "brainflammation" that's behind the beneficial effects of statin drugs.

Those who take statins can benefit from eating pomegranate | learn more

What is more or less undebatable, though, is that "there is insufficient evidence to recommend statins for the treatment of dementia" (McGuinness. 2013). I will leave you with this conclusion from the latest Cochrane review and a discreet reference to the influence of APO-E phenotypes on both baseline cholesterol levels and the development of Alzheimer's disease. Who knows? If we controlled for the APO-E4 allele, we may well find that carriers of the AA (=2x positive) form of the APO-E4 gene, of which a recent study from the University of Toronto suggests that having this homozygous APO-E4 gene poses a 56.0x higher risk (no typo!) of developing dementia (all forms), benefit from taking a statin while others don't? I will obviously keep you posted on all future developments.

References:

Aparicio Vizuete A, Robles F, Rodríguez-Rodríguez E, López-Sobaler AM, Ortega RM. Association between food and nutrient intakes and cognitive capacity in a group of institutionalized elderly people. Eur J Nutr. 2010 Aug;49(5):293-300.
Barberger-Gateau P, Letenneur L, Deschamps V, Pérès K, Dartigues JF, Renaud S. Fish, meat, and risk of dementia: cohort study. BMJ. 2002 Oct 26;325(7370):932-3.
Deane R, Singh I, Sagare AP, Bell RD, Ross NT, LaRue B, Love R, Perry S, Paquette N, Deane RJ, Thiyagarajan M, Zarcone T, Fritz G, Friedman AE, Miller BL, Zlokovic BV. A multimodal RAGE-specific inhibitor reduces amyloid β-mediated brain disorder in a mouse model of Alzheimer disease. J Clin Invest. 2012 Apr 2;122(4):1377-92.
Fantini J, Yahi N, Garmy N. Cholesterol accelerates the binding of Alzheimer's β-amyloid peptide to ganglioside GM1 through a universal hydrogen-bond-dependent sterol tuning of glycolipid conformation. Front Physiol. 2013;4:120. doi: 10.3389/fphys.2013.00120.
Liu R, Wu CX, Zhou D, Yang F, Tian S, Zhang L, Zhang TT, Du GH. Pinocembrin protects against β-amyloid-induced toxicity in neurons through inhibiting receptor for advanced glycation end products (RAGE)-independent signaling pathways and regulating mitochondrion-mediated apoptosis. BMC Med. 2012 Sep 18;10:105.
Hosaka A, Araki W, Oda A, Tomidokoro Y, Tamaoka A. Statins reduce amyloid β-peptide production by modulating amyloid precursor protein maturation and phosphorylation through a cholesterol-independent mechanism in cultured neurons. Neurochem Res. 2013 Mar;38(3):589-600.
Hung YH, Bush AI, La Fontaine S. Links between copper and cholesterol in Alzheimer's disease. Front Physiol. 2013;4:111.
Matsuzaki T, Sasaki K, Hata J, Hirakawa Y, Fujimi K, Ninomiya T, Suzuki SO, Kanba S, Kiyohara Y, Iwaki T. Association of Alzheimer disease pathology with abnormal lipid metabolism: the Hisayama Study. Neurology. 2011 Sep 13;77(11):1068-75.
Nandhini AT, Thirunavukkarasu V, Anuradha CV. Stimulation of glucose utilization and inhibition of protein glycation and AGE products by taurine. Acta Physiol Scand. 2004 Jul;181(3):297-303.
Ozawa M, Ninomiya T, Ohara T, Doi Y, Uchida K, Shirota T, Yonemoto K, Kitazono T, Kiyohara Y. Dietary patterns and risk of dementia in an elderly Japanese population: the Hisayama Study. Am J Clin Nutr. 2013 May;97(5):1076-82.
Reis PA, Estato V, da Silva TI, d'Avila JC, Siqueira LD, Assis EF, Bozza PT, Bozza FA, Tibiriça EV, Zimmerman GA, Castro-Faria-Neto HC. Statins decrease neuroinflammation and prevent cognitive impairment after cerebral malaria. PLoS Pathog. 2012 Dec;8(12):e1003099.
Silva T, Teixeira J, Remião F, Borges F. Alzheimer's disease, cholesterol, and statins: the junctions of important metabolic pathways. Angew Chem Int Ed Engl. 2013 Jan 21;52(4):1110-21.
Song Y, Nie H, Xu Y, Zhang L, Wu Y. Association of statin use with risk of dementia: A meta-analysis of prospective cohort studies. Geriatr Gerontol Int. 2013 Mar 6.
Steenland K, Zhao L, Goldstein FC, Levey AI. Statins and cognitive decline in older adults with normal cognition or mild cognitive impairment. J Am Geriatr Soc. 2013 Sep;61(9):1449-55.

Coffee - 3 Cups Per Day Keep Insulin at Bay: You Better Start Today if You Want to Retain Your Insulin Sensitivity, and Stay Cancer & CVD Free Beyond Your Own Centennial!

I am not entirely sure how often I have used the sentence "consistency is key", here at the SuppVersity, but there is no way I don't reiterate it in the context of the never-ending debate over the pros and cons of habitual coffee drinking, once again. While much of the experimental evidence would suggest that coffee, or to be precise, caffeine the major methylxanthine in the brown brew is a bad sympathetic nervous system activator that stresses your body and will deteriorate your glucose and fat metabolism, the majority of the epidemiological evidence points into the exact opposite direction.

A paper that's going to be published in the next issue of AGE the Journal of the American Aging Association could however help not just to bridge the widening gap between the ever-increasing number of epidemiological studies showing between moderate caffeine consumption and metabolic, cardiovascular, neurological, and cellular health (see list at the end of this post) and the conflicting evidence from experiments that investigate the acute response to caffeine ingestion in both caffeine-naive individuals and habitual caffeine consumers.

Consistent caffeine consumption is the key to "chronic health" ;-)

I am pretty sure this study won't close the lit on the never-ending debate about the pros and cons of caffeine consumption - mostly because it's a rodent study, but also in view of the fact that there is no definite border between "habitual consumption" and "chronic abuse", when it comes to a substance the stimulating side-effects of which can keep you functioning (and training!), when your body would otherwise long have called a halt.

Against that background it is important to realize that the rodents in the study at hand were leading a happy, more or less stress-free life. They consumed what you would consider a "healthy" diet for a rodent and had free access to a wheel, the average male and female Wistar who has neither television, nor Internet or a PlayStation in his or her cage, will actually make good use of.

Figure 1: Body weight (in g), visceral fat weight (in g/kg body weight) and skeletal muscle glucose transporter 4 expression (GLUT4 activity relative to glucose breakdown) over the course of 24 months with or without the provision of the human equivalent of caffeine of roughly 3 cups of coffee in the drinking water (data based on Guarino. 2012)

Accordingly, you should not wonder, let alone be disappointed that there is no magical "fat destruction" such as the one we've seen about a months ago in the CLA-study (see "CLA Destroys Body Fat: Effect Borders Pathological Lipodystrophy!"). Remember: Consistency is key! And some of the benefits of today's coffee may not show before you are in your late 70s... but let's get back to the results data from figure 1 and their implications for your current and future health:

Additional observations:

the decrease in visceral fat mass was not due exclusively to increased lipolysis
the increase in insulin sensitivity induced by caffeine was not attributable to weight loss, increased NO production, caffeine-mediated antioxidant effects, decreased cortisol levels, or decreased SNS activity
caffeine intake did not modify blood pressure, endogenous NO production, or antioxidant capacity in aged animals
caffeine administration restored Glut4 expression in the elderly group, but it was not able to increase Glut4 expression above amaximal level in the 12Mgroup

the rodents were kept on a normal diet, a healthy body weight is thus only a sign of overall metabolic health (remember: skinnier does not equal healthier!),
the 42% lower visceral fat levels in what would be middle aged rodents (12 months) is one of the most significant predictors of healthy aging (optimal brain and metabolic health + no cancer), and
the maintenance of skeletal muscle GLUT4 expression is of fundamental importance to ward of those increasingly common "age-related" diseases of which we already know that they are at least precipitated by insulin resistance and high glucose levels, such as Alzheimer's and "regular" dementia (e.g. Rönnemaa. 2008; Accardi. 2012; Williamson. 2012)

Against the background of the previously mentioned conflict between experimental (caffeine induces stress and thwarts glucose and fatty acid metabolism) and epidemiological (caffeine correlates with metabolic health) evidence it is also important to mention that these beneficial effects were not negated by the dreaded stress-induced increases in non-esterified fatty acids (NEFA), which is the most commonly heard argument of the opponents of caffeine / coffee consumption. On the contrary, the ...

"[...] increase in insulin sensitivity induced by caffeine was not attributable to weight loss, increased NO production, caffeine-mediated antioxidant effects, decreased cortisol levels, or decreased SNS activity [so that caffeine effectively] restored [otherwise elevated] circulating NEFA in aged animals to values observed in young 3 M control rats." (Guarino. 2012)

In the absence of increased NEFA levels, an increased sympathetic tone (=higher catecholamine and cortisol levels) and in the presence of optimal GLUT-4 expression and low visceral fat levels in the young and middle aged rodents, there is actually no reason why we would see any of the putative negative effects on glucose metabolism of about which you will probably have read and heard numerous times in the laypress.

Figure 2: Glucose clearance during ITT (in % glucose/min), basal plasma and insulin levels (in mM) over the course of 24 months (basically one rodent lifespan) with or without the provision of the human equivalent of caffeine of roughly 3 cups of coffee in the drinking water (data based on Guarino. 2012)

And, as a matter of fact, the data in figure 2 does confirm just that: The chronic administration of caffeine at a dosage of which the researchers state, that it will generate plasma caffeine levels "comparable to those in moderate to low consumers of caffeinated beverages" (Guarino. 2012), i.e. people who drink about 3 cups of the delicious brew per day (300-500mg caffeine; Gasio. 2002), is probably one of the most delicious and convenient ways to ward off age-related declines in glucose tolerance... this does yet not mean that drinking coffee (let alone Coke or energy drinks) could make up for a sedentary lifestyle and (ab-)using caffeine pills and stims to keep functioning will probably even have the opposite effects.

Glucose management figures everywhere and so does coffee!

Did you know that the data from a recently published trial suggests that "14-day caffeine supplementation [at 5mg/kg body weight] can probably decrease exercise-induced inflammatory response (CRP elevation and Leukocytosis) following 30 min downhill running in male non-athletes" (Jafari. 2012)? That's actually pretty intruiging, as it shows that the already mentioned differences between the chronic and acute effects of trimethylxanthie aka caffeine are not restricted to its effect on overall and metabolic health, especially as, caffeine has hitherto not exactly been known as a an ergogenic the effects of which build up over time... in fact, rather the opposite is usually assumed, although the evidence for the decline of the ergogenic (not the stimulant!) effects of caffeine are still inconclusive.

In view of the major role of glucose management in all sorts of the metabolic, endocrine and neurcrine diseases, it is thus no wonder that study after study finds beneficial effects of moderate caffeine consumption on...

risk of heart failure (Mostofsky. 2012)
perceptibility to arrhythmia (Klatsky. 2011)
venous thromboembolism (Enga. 2011)
general cardiovascular disease (Bøhn. 2012)
dementia & Parkison's (Cao. 2012; Campdelacreu. 2012)
diabesity (Hjellvik. 2011; Matsuura. 2012)
pancreatic cancer (Dong. 2011), as well as
bladder, breast, buccal and pharyngeal cancer (Yu. 2011)
colorectal, endometrial, esophageal cancer (Yu. 2011)
hepatocellular, leukemic, and prostate cancers (Yu. 2011)

And though, I could certainly extend this list by a dozen or so references for each item and half a dozen additional items, I guess I'd rather end today's blogpost on the note that coffee (and tea) contain way more than just caffeine. I would therefore suggest you don't rely on caffeine alone, but rather grab yourself an old-fashioned black cup of coffee (ad some creme if you can't stand it black, or coconut oil, if you like that better) and the time it takes to savor the aroma and taste of it... I can guarantee: That will exponentiation its health effects and will allow you to catch up on the 5 minutes you may have lost in no time.

References:

Accardi G, Caruso C, Colonna-Romano G, Camarda C, Monastero R, Candore G. Can Alzheimer disease be a form of type 3 diabetes? Rejuvenation Res. 2012 Apr;15(2):217-21.
Bøhn SK, Ward NC, Hodgson JM, Croft KD. Effects of tea and coffee on cardiovascular disease risk. Food Funct. 2012 Jun;3(6):575-91.
Campdelacreu J. Parkinson disease and Alzheimer disease: environmental risk factors. Neurologia. 2012 Jun 13.
Cao C, Loewenstein DA, Lin X, Zhang C, Wang L, Duara R, Wu Y, Giannini A, Bai G, Cai J, Greig M, Schofield E, Ashok R, Small B, Potter H, Arendash GW. High Blood caffeine levels in MCI linked to lack of progression to dementia. J Alzheimers Dis. 2012;30(3):559-72.
Dong J, Zou J, Yu XF. Coffee drinking and pancreatic cancer risk: a meta-analysis of cohort studies. World J Gastroenterol. 2011 Mar 7;17(9):1204-10.
Enga KF, Braekkan SK, Hansen-Krone IJ, Wilsgaard T, Hansen JB. Coffee consumption and the risk of venous thromboembolism: the Tromsø study. J Thromb Haemost. 2011 Jul;9(7):1334-9.
Gasior M, Jaszyna M,Munzar P,Witkin JM, Goldberg SR. Caffeine potentiates the discriminative-stimulus effects of nicotine in rats. Psychopharmacology (Berl). 2002; 162:385–395
Guarino MP, Ribeiro MJ, Sacramento JF, Conde SV. Chronic caffeine intake reverses age-induced insulin resistance in the rat: effect on skeletal muscle Glut4 transporters and AMPK activity. Age (Dordr). 2012 Sep 14.
Hjellvik V, Tverdal A, Strøm H. Boiled coffee intake and subsequent risk for type 2 diabetes. Epidemiology. 2011 May;22(3):418-21.
Jafari A, Kherad N, Melekirad AA. Effect of short-term caffeine supplementation on downhill running induced inflammatory response in non-athletes. Journal of Cell. Winter 2012; 2(4):377-385
Klatsky AL, Hasan AS, Armstrong MA, Udaltsova N, Morton C. Coffee, caffeine, and risk of hospitalization for arrhythmias. Perm J. 2011 Summer;15(3):19-25.
Matsuura H, Mure K, Nishio N, Kitano N, Nagai N, Takeshita T. Relationship between coffee consumption and prevalence of metabolic syndrome among Japanese civil servants. J Epidemiol. 2012;22(2):160-6.
Mostofsky E, Rice MS, Levitan EB, Mittleman MA. Habitual coffee consumption and risk of heart failure: a dose-response meta-analysis. Circ Heart Fail. 2012 Jul 1;5(4):401-5. Epub 2012 Jun 26.
Nature.com Reviews. Heart failure: Moderate coffee consumption linked with reduced risk of HF. Nat Rev Cardiol. 2012 Jul 17;9(9):492.
Rönnemaa E, Zethelius B, Sundelöf J, Sundström J, Degerman-Gunnarsson M, Berne C, Lannfelt L, Kilander L. Impaired insulin secretion increases the risk of Alzheimer disease. Neurology. 2008 Sep 30;71(14):1065-71.
Williamson R, McNeilly A, Sutherland C. Insulin resistance in the brain: An old-age or new-age problem? Biochem Pharmacol. 2012 Sep 15;84(6):737-45.
Yu X, Bao Z, Zou J, Dong J. Coffee consumption and risk of cancers: a meta-analysis of cohort studies. BMC Cancer. 2011 Mar 15;11:96.

Use HMB to Improve Your "Muscle Quality", Training to Build Muscle and Training + HMB to Cut Body Fat. It Works For the Elderly Will It Also Work for You?

This is Ernestine Shepherd; and while Ernestine is not one of the study subjects she would qualify. After all, she is 74. And she is also something else: An example of the anti-aging effects of life-long exercise and sensible nutrition.

HMB has gotten back to the limelight lately. Many scientists are currently working on advanced preparations with increased or faster absorption rates. A soon-to-be-published study in the Journal of Experimental Gerontology does however suggest that the latter may - at least for some basic and certainly non-negligible effects in the aging muscle and adipose tissue - not even be necessary. For these purposes the good old (and disgustingly tasting) CaHMB powder us Europeans can get for cheap at every street corner appears tow work quite fine.

In a randomized controlled study, the Jeffrey R. Strout and his colleages from the University of Central, the University of North Carolina, the Georgia Southern University, the United States Sports Acadamy, and the University of Tampa, observed that the 3g of "good old" calcium-β-hydroxy-β-methylbutyrate (CaHMB) works just fine to increase leg strength and muscle quality in >65yr old subjects.

To be able to evaluate the effects of HMB alone and in combination with strength training, the scientists divided the study into two main phases:

Phase I consisted of two non-exercise (NE) groups: (a) ad libitum diet plus placebo (NEPLA) and (b) ad libitum diet plus CaHMB (NEHMB).
Phase II consisted of two resistance exercise (RE) groups: (a) ad libitum diet plus placebo and resistance exercise (REPLA) and (b) ad libitum diet plus CaHMB and resistance exercise (REHMB).

The study evaluation period for each participant in Phases I and II was 24 weeks. Testing was performed at week 0 (pre-test), 12 weeks (mid-test), and 24 weeks (post-test), and consisted of body composition (the scientists used reliable DXA scans to assess the lean mass and body fat levels), muscle strength, functional movement, three-day dietary recall, blood markers, and urinalysis for HMB consumption.

2x1.5g + 4g carbs did the trick

Muscle quality (MQ) - what is that? "Muscle quality (MQ) was calculated as muscle strength relative to muscle mass. MQ has been used and described previously as an indicaor of muscle function (Lynch et al., 1999; Tracy et al., 1999)." (Strout. 2013) Being a measure of strength relative to muscle mass, MQ is considered a predictor of health status, mortality and a better indicator of muscle function than strength alone (spec. the hilarious grip strength measures you see in many studies in geriatric journals).

The supplement had to be consumed with a non-alcoholic drink at least 2x per day. In addition to the HMB or placebo powder it contained an additional 4g of carbs (I am mentioning this, because it cannot be excluded that this had a minimal effect on the absorption or metabolism of HMB). The resistance training sessions (RE) in the 2nd phase of the study were performed three times per week. The volume of the training sessions (number of sets per exercise per week) was as follows (quoting directly from Strout. 2013):

week 1 was pre-testing only,
weeks 2 and 3 included one set per exercise,
week 4 was two sets,
weeks 5–10 were three sets,
week 11 was one or two sets,
week 12 was mid-testing only,

weeks 13 and 14 were one set,
week 15 was two sets,
weeks 16–22 were three sets,
week 23 was one or two sets, and week 24 was post-testing, only.

During each training session, all participants completed one to three sets of 8–12 repetitions for each exercise.

Exercises included the bench press, lat pulldown, bilateral leg press, hack squat, and bilateral leg extension. The subjects rested for 2-5min between the exercises and used a classic linear progression (+2-4kg), whenever they felt comfortable performing their exercises with 12 reps at their previous training weight.

Figure 1: Changes in body composition in response to phase 1 (no exercise) and phase 2 (resistance training) of the 2x 12 week intervention study (Strout. 2013)

If you look at the data in figure 1 you will see that the major driving force behind the changes in body composition was not the supplementation regimen. As Strout et al. point out, both HMB alone, as well as its combination with resistance training did however yield statistically significant changes in the muscular architecture of the 72-73 (+/-1) year old subjects (for an explanation of the parameter "muscle quality" see info-box above):

The fat loss certainly reminds me of the recent leucine + B6 study
"Phase I of the current study demonstrated that prolonged supplementation with CaHMB [alone] improved total lean mass (LM), strength, function and MQ without resistance exercise.

In addition, the progressive, high-intensity resistance training protocol used in Phase II resulted in increased LM, strength, and MQ, with or without CaHMB.

Moreover, the CaHMB intervention in Phase II resulted in a significant decreased total fat mass along with the increased total lean mass and arm MQ from the training."

What I consider particularly interesting, here, is the statistically significant increase in fat loss, which is certainly not the first thing you may be thinking about, when it comes to HMB supplementation. In a way this reminds me of the astonishing effects Zemel et al. observed in their recently published Leucine + B6 study (see corresponding SuppVersity article from August 31) and would support the notion that leucine and/or its metabolite HMB increase the oxidative capacity of skeletal muscle - at least in situations of increased cellular stress (obesity in the Zemel study or training in the study at hand; see as well "Leucine + Resveratrol - Synergistic Sirtuin Boosters: +118% Fatty Acid Oxidation, 60% Increase In Muscular Glucose Uptake, -30% Visceral Fat & More - To Good to be True? | read more"). In this context, Strout et al. write:

"One interesting finding regarding the CaHMB treatment in the present study was its effect on fat mass, which was consistent with Vukovich et al. (2001). CaHMB alone did not cause fat loss. However, resistance training with or without CaHMB resulted in a significant loss of fat mass at week 12, whereas only the CaHMB group was able to further the reduction in fat mass at week 24." (Strout. 2013)

They then make a questionable statement about how "resistance exercise is not thought to be a potent stimulus for total body fat loss", but get back on track when they add:

"[...] recent evidence suggested that CaHMB supplementation improved fatty acid oxidation, adenosine monophosphate kinase (AMPK), and Sirt1 and Sirt3 activity in adipocytes and in muscle cells (Bruckbauer. 2012). Collectively, these proteins act to improve mitochondrial biogenesis, fat oxidation, and energy metabolism." (Strout. 2013)

This would support my own hypothesis that the fat loss is mainly a function of mitrochondrial activity / increases in mitochondrial capacity. And while it has to be determined whether similar effects can be observed in non-muscle cells, even he local improvement of mitochondrial biogenesis would have beneficial downstream effects on whole body metabolism - including the brain!

If you want to learn more about the usefulness of HMB, I suggest take (another) look at my article about the results of a 2012 dissertation (read more)! And a previous report in the short news about the difference between leucine & HMB (read more)

Bottom line: Smart best-agers are good advised to make sure to get their daily dose of good ol' Calcium-HMB: I guess, I could actually leave it with that if there were not a couple of questions left to address:

Will these effects occur in individuals on "high" (=2xRDA) protein diets, as well?
Will they add to the beneficial effects a regular whey protein has to offer?
Is age critical to benefit or are we going to see the same, improved or smaller effects in younger individuals, as well?

While it really seems that we have been missing out on a highly useful supplement that has been available for years, there is still some research to be done, before these questions can be answered with the necessary confidence.

A note on protein requirements in the elderly: Did you know that the current recommended protein intake for the elderly is 0.6g/kg body mass and that Campbell et al. were able to show that at least 1.0g/kg is needed simply to maintain a normal nitrogen balance ? No, well now that you know the 1.1g/kg baseline protein intake in the study at hand tell you what kind of scenario we are talking about - one of protein adequacy, at best!

In my humble opinion the latter is specifically true with respect to questions (1) and (2) as corresponding data is hitherto simply non-existent. So we are hard pressed to tell whether you can achieve identical or at least similar body recompositioning effects by simply adding a whey protein shake or protein bar that is not 80% sugar to the diets of our unfortunately protein-underfed "best agers".

On the other hand, previous studies in trained athletes, as well as the user feedback due to which HMB more or less disappeared from the market would suggest that this definitely is the case for younger folks, meaning the usefulness of regular, slow digested calcium HMB in the context of an already highly optimized training and nutritional regimen in people who do not have to fight the age-induced continuant catabolism is more than questionable.

References:

Bruckbauer A, Zemel MB, Thorpe T, Akula MR, Stuckey AC, Osborne D, Martin EB, Kennel S, Wall JS. Synergistic effects of leucine and resveratrol on insulin sensitivity and fat metabolism in adipocytes and mice. Nutr Metab (Lond). 2012 Aug 22;9(1):77.
Stout JR, Smith-Ryan AE, Fukuda DH, Kendall KL, Moon JR, Hoffman JR, Wilson JM, Oliver JS, Mustad VA. Effect of calcium β-hydroxy-β-methylbutyrate (CaHMB) with and without resistance training in men and women 65+yrs: A randomized, double-blind pilot trial. Exp Gerontol. 2013 Aug 24.
Vukovich MD, Stubbs NB, Bohlken RM. Body composition in 70-year-old adults responds to dietary beta-hydroxy-beta-methylbutyrate similarly to that of young adults. J Nutr. 2001 Jul;131(7):2049-52.

DHEA Revives Liver of Aged Rats and Improves Antioxidant Reserves and Akt Signaling in Young and Old Rats.

Image 1: I don't think celebrities realize it, but there is more to anti-aging than an unlined face. New studies show that DHEA could after all help with all sorts of age related diseases (img. antiagingpossible.com)

It's been a while since DHEA was in the news. While I have posted a handfull of mostly beneficial findings related to dehydroepitestosterone (DHEA), the hype that sourrounded its purported anti-aging effect in the late 1990s has completely abated. In view of DHEA's implication (or rather the lack of the latter) in age-related autoimmune disease, sexual disfunction, osteoporisis, deteroiations of lipid metabolism, type 2 diabetes and cardiovascular and liver disease (Basci. 2007- igniﬁcance of dehydroepiandrosterone and dehydroepiandrosterone sulfate in different diseases), it is questionable how people beyond the age of 40, when DHEA production declines by 2% per year(!) could not benefit from a carefully planned and monitored DHEA treatment. A group of scientists from Brazil obviously thought the same and decided to take a fresh look at what happens on a molecular level, when 3 (young rats) and 24 months (old rats) old male Wistar-rats are given 10mg/kg deyhdroepitestosterone [human equivalent: 1.62mg/kg; 80kg human: 130mg/day] subcutaneously per day for 5 weeks (Jacob 2011).

Figure 1: Relative changes in total, reduced and oxidized glutathione in young and old rats after 5 weeks on 10mg/kg DHEA (data adapted from Jacob 2011)

As you can see in figure 1, the treatment induced profound increases in total and reduced glutathione and age-dependendly increased (young) or decreased the absolute level of oxidized glutathione (GSSG). Despite the absolute increase in GSSG, usually a marker of oxidative stress, the more important GSH / GSSG ratio, i.e. the ratio of reduced to oxidized glutathion, a more comprehensive marker of the balance of pro- vs. anti-oxidant metabolic processes, improved even more in the twelve young rats, (+6% GSH/GSSG) than in their older companions (+1% GSH/GSSG).

Figure 2: p-Akt levels in young and old rats with and without DHEA supplementation (data adapted from Jacob 2011)

As a faithful student of the SuppVersity, the serine/threonine kinase Akt should not be a stranger to you, after all, mTOR and p706SK (the "muscle builders", you've read about in the context of BCAAs, leucine and exercise-induced protein synthesis), are among its intracellular substrates. In agreement with previous studies, chronic administration of DHEA increased p-Akt-expression in the study at hand (cf. figure 2). The scientists speculate "that the Akt activation in this organ [the liver] is a protective answer" and could, after all, be the underlying reason for the preservation / restauration of hepatic function in the old rats.

Image 2: Oral DHEA supplements are sold for a few bucks over-the-counter (at least in the USA). Yet,
esp. for people under the age of 35, it probably does not make sense to buy and use those. At least, for
as long as it takes for the results of the study at hand to be confirmed in humans. And the allegedly benign 7-Keto DHEA could wreak havoc on your natural corticosteroid metabolism.

So how much DHEA should I take? Given the fact that the name of this blog is SuppVersity, I should have apprehended DeDeRa's question on which form and how much DHEA I would suggest you take. My answer is quite simple: NONE! Why? Well, this is a rodent study done with injectable DHEA. Not only would it be imprudent to extrapolate any dosing suggestions for oral DHEA supplements in humans, without clinical tests, we cannot even be sure that the effects would be identical, even if we hit the right dosage. Thus, while I am convinced that DHEA is probably more benign than many other OTC "supplements", especially people under the age of 30-35 should think twice or better thrice before popping any DHEA supplement - this includes 7-keto, the cortisol-suppressant effects of which can wreak havoc on your natural corticosteroid balance, make you feel tired and sluggish and deprive your body of an important anti-inflammatory pathway.

Most importantly, however, the study does away with the longstanding prejudice that DHEA (at the given dosage) "represent[s] a toxic potential to [the] liver". The isolated finding that endogenous DHEA lead to increased oxidation in the liver (it still does, but the overall pro- vs. anti-oxidant balance still improves!), as well as insufficient funding by the pharmaceutical industry, who obviously is not interested in naturally occuring and thus non-patentable treatment methods, had been one of the primary reasons many scientists decided not to dig deeper into the ameliorative, preventive and restaurative effects of DHEA in the context of age-related diseases. Personally, I hope that the few new studies that have been published, lately, will encourage other researchers to have another look at a hormone with profound yet complex and complicated effects on numerable aspects of the mammalian metabolism.

Fasting or Caloric Restriction, What Holds Greater Promise as a Means of Life Extension? Plus: Does Exercise "On Empty" Increase Muscle Damage?

"70 Years Between Meals? Indian Mystic Promotes Atmosphere Diet" that's the title of a Times newsfeed, but is it also the secret to longevity? Or is 70 years too much of an intermittent fast ;-)?

It is undeniable that many of the centenarians are known for their rather modest energy intake and is has been long established that there is a direct mechanistic connection between "living on the high energy fast track" and increased aging. The border between calorie restriction on the one hand and malnutrition on the other is however fluid and where one may effectively add a couple of years to your life-span the other is not only going to make it shorter, it will also make it miserable. Within the past years fasting and intermittent fasting have emerged as potential alternatives.

The purpose of today's article is now to take a closer look on whether they are equally or better suited to lead a long, healthy life that is not going to wast you away.

Longevity effect of caloric restriction: More than a long-lived myth?

Scientists were pretty excited, when the first realized that a reduction in caloric intake without malnutrition, will initiate metabolic adaptations that can extend the lifespan of a variety of species.

"Key early studies in rodents revealed that mice fed 55–65% caloric restricted diets through their life exhibited a 35–65% greater mean and maximal lifespan than mice eating a non-purified ad libitum diet (Weindruch. 1996). Although attenuated, these effects remain present even when moderate caloric restriction (20–40%) is implemented in middle-aged mice (Weindruch. 2001)."

At least in rodents (Weinbruch. 2001) and nonhuman primates (Colaman. 2009) these beneficial effects on life expectancy were partly mediated by reductions of exactly those diseases that are currently carrying off increasing parts of the population of the Western Obesity Belt, namely cancer and diabetes.

Insulin surprise: Higher not lower fasting insulin levels are associated with better cognitive performance in Chinese nonagenarians and centenarians. At the same time, the worst cognitive function was found in subjects with hypoglycemic (=low) blood glucose levels (Yan-Ling. 2013).

Evidence that similar beneficial effects can occur in human beings comes mostly from studies on overweight subjects on calorically restricted diets. Unsurprisingly, the latter have been associated with

reductions of several cardiac risk factors (Fontana. 2004 + 2007; Lefevre. 2009),
improved insulin-sensitivity (Larson-Meyer. 2006), and
enhanced mitochondrial function (Civitarese. 2007).

These health improvements went hand in hand with a reduction in oxidative DNA damage (Heilbronn. 2003 + 2006; Hofer. 2008), but support the benefits of general caloric reduction only in those who have been eating well than they needed for years.

But what about the healthy, lean physical culturist?

Those of you who have already tried to live off a calorically reduced diet for months, may however have noticed that this does come with significant downsides for the someone who does not carry a health-deteriorating, but "nourishing" (in times of caloric reduction) amount of body fat around. For those increasingly rare specimen without a pouch, an intermittent, instead of a chronic caloric reduction and / or a fasting regimen appears to be a much more favorable way to slow down the clock that's ticking for all of us.

"Evidence that [fasting for hours and up to days] may have beneficial effects on longevity first appeared several decade ago (Carlson. 1946). Since this time, a growing body of literature suggests that fasting periods and intermittent fasting regimens can trigger similar biological pathways as caloric restriction (i.e., increased autophagy and mitochondrial respiratory efficiency), which can result in a host of beneficial biological effects including increased circulation and cardiovascular disease protection, and modulation of reactive oxygen species and inflammatory cytokines (Lee. 2011)" (Anton. 2013)

Fasting periods have also been shown to have direct antimutagenic, antibacterial and anticarcinogenig effects (Lee. 2011). In a recent special on the effects of fasting on all things longevity & health in the Journal of Experimental Gerontology, there are three different papers with direct relevant to the topic:

Suggested read: "More Muscles For Old Chaps, Less Fat for Baby Boomers W/ HMB" | read more
Waters et al. did a review of the controversies related to current lifestyle recommendations promoting diet-induced weight loss in obese adults 65 years and older (Waters. 2013).

Obesity in those > 65 years of age is prevalent and linked to negative health outcomes. The review found that diet & exercise facilitate weight loss in frail obese older adults.

Muscle quality and physical function improved with weight loss. The weight loss observed in all studies included bone & lean body mass, issues to be addressed in future studies, this as well as the unsatisfying long-term effects argue against the current use of chronically energy-reduced diets in the elderly.
Avena et al. compared the effects of both food restriction and overeating on brain reward systems (Avena. 2013).

The aging population has been shown to exhibit altered reward sensitivity and decreased caloric consumption. Moreover, members of this population appear to be increasingly affected by the current obesity epidemic. Food, like alcohol or drugs, can stimulate its own consumption and produce similar neurochemical changes in the brain. Age-related loss of appetite, decreased eating, and caloric restriction are hypothesized to be associated with changes in the prevalence of substance misuse, abuse, and dependence seen in this cohort.

Overall, the results appear to suggest that the hedonistic effects of eating play an important role with respect to the impact our diets can have on longevity, as well. And in that, malnutrition in response to anorexia is as detrimental to our health as gluttony.
Suggested read: "Sugar Addicted or Just Stressed Out? Study Investigates Modulatory Effects of Different Macronutrient Compositions on Serotonin in the Presence and Absence of Stress" | read more
Shriner et al. revisited the concepts of "detox and abstinence" as they relate to food addition, as well as the effects of abstinence on clinical outcomes in metabolic pro-inflammatory conditions (Shriner. 2013).

The researchers point out that geriatric diabesity is confounded by the obesity paradox (healthy people with high BMI) and sarcopenia (sick people with low BMI and no muscle). Interestingly, neuroimaging results show same pattern in obese and cocaine/opioid addicts - an observation the researchers relate to the combined fat and sugar (especially HFCS) overload which is not just pro-inflammatory, but also highly addictive. For the live-long fast food junkie, fasting (chronic or intermittent) is thus the "new abstinence". To"detox" the body it does therefore require metabolic, addictive and relationship treatment in most of the patients, which is why diabese geriatric patients need careful supervision by physician and dietician.

These reviews are topped of with an intriguing study by Dannecker et al. who investigated the effects of fasting on indicators of skeletal muscle damage in humans.

Figure 1: NO (µmol/L) in 12 young female subjects (22 years) before & after biceps curls in the fasted (8h water fast during the day) and 4-5h after meal with ca. 30g / 100g / 35g fat/carbs/protein (Dannecker. 2013)

Dannecker et al. tested the effects of fasting on exercise-induced muscle damage in humans (Danecker. 2013). Daily 8-hour fasts were compared to a controlled meal within 4–5 h of visit. The indicators of muscle damage were collected before and across five days after exercise. The fasts did not robustly protect against exercise-induced muscle damage, but it did not ameliorate the damage either.

However, both the baseline and post-workout nitric oxide levels [NO] were higher (figure 1) and the TNFa levels, a marker of oxidation damage was lower in the fasting group across time. Therfore, the researchers conclude that fasting may in fact have an ameliorative effect on muscle damage.

All of these studies are relevant to the initially raised question and they appear to confirm that despite the fact that it is "currently unknown if all humans benefit from engaging in caloric restriction", the contemporarily available research supports the notion that "we" are probably all living on the metabolic fast lane.

In other words, lean or not - that's more of a matter of how much more food you consume than you actually need, or put more simply: With the current energy intake we are already at the upper end of the adaptation scale.

Suggested read: "A Low Fat Advantage For Alternate Day Fasting? While the Improvements in Body Composition Are Virtually Identical, Only the 25% Fat Diet Will Improve Arterial Blood Flow" | read more

Intermittent fasts are thus actually only bringing us back to the mid-range and closer to what would be "necessary" for weight maintenance and metabolic flexibility without having the nasty side effect of favoring permanent reductions in caloric expenditure. The latter are actually the result of our body shifting into a new "steady state" that will leave us in a position, where it is becoming increasingly hard to maintain our weight and health in a society that is characterized by 24/7 nutrient abundance and portion sizes that are way beyond good and evil. The consequence is a constant overexpression of the "anabolic", but autophagy and thus recycling / repair impairing IGF-1/p-AKT/m-TOR pathway I talked about during Thursday's installment of the Science Round-Up on SuperHumanRadio.com (download the podcast, here).

Fasting induced ravenous feasts, a potential problem!?

Contrary the controlled "intermittent fast" as it is propagated among others in the infamous "lean gains" regimen, the increasingly popular ever-other-day or two-days-a-week fasting regimen, in the course of which people tend to go totally overboard on the "feasting days", have been implicated as one of the reasons for the undeniable trend that breakfast-skippers tend to consume a low quality diet and display significantly increased obesity rates (cf. Niemeier. 2006; Deshmukh-Taskar. 2012).

The diet quality is in fact so important, that even the often hailed "Eat Breakfast Like a King and Supper Like a Pauper" appears to entail significant negative metabolic downsides for exactly those people who are now jumping on the said "intermittent fasting for dummies" train without making the most important qualitative dietary and lifestyle changes first.

In 2008, for example, Devaraj et al. observed that the ingestion of a high-fat, energy-dense, fast-food-style breakfast results in an increase in oxidative stress in metabolic syndrome people with metabolic syndrome compared to a control breakfast that was formulated according to the suggestions of the American Heart Association (Devaraj. 2008)
Figure 2: The increases in oxidation markers in response to a single large fast-food-style (FFS) breakfast counter all potential benefits of intermittent fasting (Devaraj. 2008)
As the corresponding markers of postprandial inflammation and lipid oxidation go to show you, a single-meal strategy aka "If It Fits Your Macros" that does not take food quality into considerations well, is the best way to ruin the already wrecked health of an obese individual completely.

Of the latter, namely the lifestyle changes, there is little question that the inclusion of intense (=challenging) exercise regimen will probably going to yield the most significant benefits for obese and lean individuals alike. Lee et al., for example, found statistically highly significant risk reductions in all-cause mortality, when they reviewed the data from 17 321 healthy men with a mean age of 46 years. And to achieve the -13% reduction in all-cause mortality it takes nothing, but a weekly exercise induced energy expenditure of 800-900kcal - as long as you are burning them
during exercises that consume at least >6x the amount of your resting energy expenditure.

Suggested read: "Intermittent Thoughts On Intermittent Fasting - AMPK I/III: Zoning in on Its Effects on Body Composition" | read more

Reckless IIFYM Intermittent Fasting for the sluggish obese will probably worsen, not improve the situation: Intermittent, continuous fasting and exercise are, at least from a very fundamental, mechanistic perspective equivalent. They all promote autophagy + cell-recycling over anabolism + cell differentiation.Optimal health does yet reside somewhere on a sine that oszillates between AMPK and mTOR and that is probably better served with an intermittent fasting than with a chronic fasting regimen.

Without exercise and finally getting rid of the illusory dream that you could eat "whatever you want" and "as much as you want", as long as you don't eat it "whenever you want" intermittent fasting can easily backfire - specifically for those whose already compromised health could turn an already not exactly healthy super-size meal into a highly inflammatory, pro-artherogenic binge.

On the other hand, I personally don't see significant evidence why a devoted fitness maniac and "3-meals a day person", like myself, would have to "fast" (I would rather call it not eat) for more than his regular 8-12h a day to help the AMPK pathway come into its own. When you are actually trying to cut weight, on the other hand, there are few better ways to easily "drop" 20% of your daily energy intake without even noticing it than intermittent fasting (=skipping one of these meals / preferably breakfast; learn why).

References:

Anton S, Leeuwenburgh C. Fasting or caloric restriction for Healthy Aging. Exp Gerontol. 2013 Apr 29.
Avena NM, Murray S, Gold MS. Comparing the effects of food restriction and overeating on brain reward systems. Exp Gerontol. 2013 Mar 25.
Carlson AJ, Hoelzel F. Apparent prolongation of the life span of rats by intermittent fasting. J Nutr. 1946 Mar;31:363-75.
Ceriello A. Acute hyperglycaemia: a 'new' risk factor during myocardial infarction. Eur Heart J. 2005 Feb;26(4):328-31. Epub 2004 Nov 30. Review.
Dannecker EA, Liu Y, Rector RS, Thomas TR, Sayers SP, Leeuwenburgh C, Ray BK. The effect of fasting on indicators of muscle damage. Exp Gerontol. 2012 Dec 22.
Devaraj S, Wang-Polagruto J, Polagruto J, Keen CL, Jialal I. High-fat, energy-dense, fast-food-style breakfast results in an increase in oxidative stress in metabolic syndrome. Metabolism. 2008 Jun;57(6):867-70.
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