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:
  1. 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.
  2. 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.
  3. 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 (┬Ámol/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 (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).

  • 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.
  • Deshmukh-Taskar P, Nicklas TA, Radcliffe JD, O'Neil CE, Liu Y. The relationship of breakfast skipping and type of breakfast consumed with overweight/obesity, abdominal obesity, other cardiometabolic risk factors and the metabolic syndrome in young adults. The National Health and Nutrition Examination Survey (NHANES): 1999-2006. Public Health Nutr. 2012 Oct 3:1-10. 
  • Fontana L, Meyer TE, Klein S, Holloszy JO. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6659-63. Epub 2004 Apr 19.
  • Larson-Meyer DE, Heilbronn LK, Redman LM, Newcomer BR, Frisard MI, Anton S, Smith SR, Alfonso A, Ravussin E. Effect of calorie restriction with or without exercise on insulin sensitivity, beta-cell function, fat cell size, and ectopic lipid in overweight subjects. Diabetes Care. 2006 Jun;29(6):1337-44. 
  • Lee C, Longo VD. Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients. Oncogene. 2011 Jul 28;30(30):3305-16.
  • Niemeier HM, Raynor HA, Lloyd-Richardson EE, Rogers ML, Wing RR. Fast food consumption and breakfast skipping: predictors of weight gain from adolescence to adulthood in a nationally representative sample. J Adolesc Health. 2006 Dec;39(6):842-9. Epub 2006 Sep 27
  • Waters DL, Ward AL, Villareal DT. Weight loss in obese adults 65years and older: A review of the controversy. Exp Gerontol. 2013 Feb 10.
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