Saturday, February 20, 2010

Improving Longevity with Calorie Reduction in Humans?

ResearchBlogging.orgLots of studies on rats and a few other mamals have seemed to show the benefit of caloric reduction and longevity - mainly it seems in the way that CR impacts core temperature (a bit lower is better), fasting insulin levels, and oxidative stress - that free radical stuff. Testing CR and humans is going to be trickier. So researchers a few years ago looked at simply the effects of CR on these very markers that have been hypothesised to have an effect on longevity. What their work shows is that yup, CR has these effects.

The resson i mention this piece here is that neither Alan Aaragon's 2007 critique of IF (which i've cited before as a good ref and which Chris over at conditioning resaerch has also detailed); nor have i seen the work referenced in the more recent Eat Stop Eat by Brad Pilon.

So here's the abstract; the full article is also available for free, which is nice.
JAMA. 2006 Apr 5;295(13):1539-48.
Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: a randomized controlled trial.

Heilbronn LK, de Jonge L, Frisard MI, DeLany JP, Larson-Meyer DE, Rood J, Nguyen T, Martin CK, Volaufova J, Most MM, Greenway FL, Smith SR, Deutsch WA, Williamson DA, Ravussin E; Pennington CALERIE Team.

Pennington Biomedical Research Center, Louisiana State University, Baton Rouge 70808, USA.

Erratum in:* JAMA. 2006 Jun 7;295(21):2482.

Comment in: * JAMA. 2006 Apr 5;295(13):1577-8.
CONTEXT: Prolonged calorie restriction increases life span in rodents. Whether prolonged calorie restriction affects biomarkers of longevity or markers of oxidative stress, or reduces metabolic rate beyond that expected from reduced metabolic mass, has not been investigated in humans. OBJECTIVE: To examine the effects of 6 months of calorie restriction, with or without exercise, in overweight, nonobese (body mass index, 25 to <30) men and women. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial of healthy, sedentary men and women (N = 48) conducted between March 2002 and August 2004 at a research center in Baton Rouge, La. INTERVENTION: Participants were randomized to 1 of 4 groups for 6 months: control (weight maintenance diet); calorie restriction (25% calorie restriction of baseline energy requirements); calorie restriction with exercise (12.5% calorie restriction plus 12.5% increase in energy expenditure by structured exercise); very low-calorie diet (890 kcal/d until 15% weight reduction, followed by a weight maintenance diet). MAIN OUTCOME MEASURES: Body composition; dehydroepiandrosterone sulfate (DHEAS), glucose, and insulin levels; protein carbonyls; DNA damage; 24-hour energy expenditure; and core body temperature. RESULTS: Mean (SEM) weight change at 6 months in the 4 groups was as follows: controls, -1.0% (1.1%); calorie restriction, -10.4% (0.9%); calorie restriction with exercise, -10.0% (0.8%); and very low-calorie diet, -13.9% (0.7%). At 6 months, fasting insulin levels were significantly reduced from baseline in the intervention groups (all P<.01), whereas DHEAS and glucose levels were unchanged. Core body temperature was reduced in the calorie restriction and calorie restriction with exercise groups (both P<.05). After adjustment for changes in body composition, sedentary 24-hour energy expenditure was unchanged in controls, but decreased in the calorie restriction (-135 kcal/d [42 kcal/d]), calorie restriction with exercise (-117 kcal/d [52 kcal/d]), and very low-calorie diet (-125 kcal/d [35 kcal/d]) groups (all P<.008). These "metabolic adaptations" (~ 6% more than expected based on loss of metabolic mass) were statistically different from controls (P<.05). Protein carbonyl concentrations were not changed from baseline to month 6 in any group, whereas DNA damage was also reduced from baseline in all intervention groups (P <.005). CONCLUSIONS: Our findings suggest that 2 biomarkers of longevity (fasting insulin level and body temperature) are decreased by prolonged calorie restriction in humans and support the theory that metabolic rate is reduced beyond the level expected from reduced metabolic body mass. Studies of longer duration are required to determine if calorie restriction attenuates the aging process in humans.

Now, i haven't seen a comparison of these same markers considered in a study where folks are JUST exercising and eating right (say a la precision nutrition's principles), but that is what folks like Aragon suggest - that exercise and diet have the same effects. A head to head study or gathering of results would be nice.

There is a nice 2009 follow up study by this group that looks at metabolic adaptation of folks on CR and CR + exercise. Bottom line: the folks who keep exercising while on the CR do not experience a metabolic adaptation like the *just * CR's (in other words the CR's metabolism really drops, and so does their activity). IS that maintenance good for longevity markers? not clear. But in terms of weight loss maintenance, surprise surprise:
Interestingly, despite similar body mass and composition changes, CR in conjunction with exercise (CR+EX) did not result in a metabolic adaptation. If weight relapse does occur in part as a result of a reduced metabolic rate in the weight reduced state, then perhaps the combination of CR and exercise may be the best choice of intervention to prevent weight regain in overweight and obese individuals. Certainly, more than 20 years ago, Pavlou observed that exercise during a CR-induced weight loss program was essential for success of weight loss maintenance [34]. Since then others have shown with doubly labeled water studies that weight stability following weight loss is sustained by higher levels of activity related energy expenditure and free-living physical activity [35], [36]. To our knowledge no studies have prospectively studied the energetic adjustments of CR only versus CR in conjunction with exercise during weight loss and weight loss maintenance.

SO diet, combined with exercise is still a good thing for maintaining ongoing body comp goals. Great.

Oh and to put icing on the cake of why exercise with diet (spliting the total CR between diet and exercise) is a good thing, the gang just published a study showing that while fat loss is the same no matter how you get you mojo on and calories off, with exercise is better:

Med Sci Sports Exerc. 2010 Jan;42(1):152-9.
Caloric restriction with or without exercise: the fitness versus fatness debate.

Larson-Meyer DE, Redman L, Heilbronn LK, Martin CK, Ravussin E.

Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA.

There is a debate over the independent effects of aerobic fitness and body fatness on mortality and disease risks. PURPOSE: To determine whether a 25% energy deficit that produces equal change in body fatness leads to greater cardiometabolic benefits when aerobic exercise is included. METHODS: Thirty-six overweight participants (16 males/20 females) (39 +/- 1 yr; 82 +/- 2 kg; body mass index = 27.8 +/- 0.3 kg x m2, mean +/- SEM) were randomized to one of three groups (n = 12 for each) for a 6-month intervention: control (CO, weight-maintenance diet), caloric restriction (CR, 25% reduction in energy intake), or caloric restriction plus aerobic exercise (CR + EX, 12.5% reduction in energy intake plus 12.5% increase in exercise energy expenditure). Food was provided during weeks 1-12 and 22-24. Changes in fat mass, visceral fat, VO2peak (graded treadmill test), muscular strength (isokinetic knee extension/flexion), blood lipids, blood pressure, and insulin sensitivity/secretion were compared. RESULTS: As expected, VO2peak was significantly improved after 6 months of intervention in CR + EX only (22 +/- 5% vs 7 +/- 5% in CR and -5 +/- 3% in CO), whereas isokinetic muscular strength did not change. There was no difference in the losses of weight, fat mass, or visceral fat and changes in systolic blood pressure (BP) between the intervention groups. However, only CR + EX had a significant decrease in diastolic BP (-5 +/- 3% vs -2 +/- 2% in CR and -1 +/- 2% in CO), in low-density lipoprotein (LDL) cholesterol (-13 +/- 4% vs -6 +/- 3% in CR and 2 +/- 4% in CO), and a significant increase in insulin sensitivity (66 +/- 22% vs 40 +/- 20% in CR and 1 +/- 11% in CO). CONCLUSIONS: Despite similar effect on fat losses, combining CR with exercise increased aerobic fitness in parallel with improved insulin sensitivity, LDL cholesterol, and diastolic BP. The results lend support for inclusion of an exercise component in weight loss programs to improve metabolic fitness.
In the meantime of waiting for the longevity marker comparison where the condition would be normal healthy eating (like PN) and exercise, there seems to be at least a few of us who are using say precision nutrition approaches to eating/health on most days (and getting questions on nutrition addressed) and ESE fasting once or twice a week - for me this protocol is an exploration; nothing definitive, but intriguing. Just FYI

Related Posts

Heilbronn, L. (2006). Effect of 6-Month Calorie Restriction on Biomarkers of Longevity, Metabolic Adaptation, and Oxidative Stress in Overweight Individuals: A Randomized Controlled Trial JAMA: The Journal of the American Medical Association, 295 (13), 1539-1548 DOI: 10.1001/jama.295.13.1539

Redman, L., Heilbronn, L., Martin, C., de Jonge, L., Williamson, D., Delany, J., Ravussin, E., & , . (2009). Metabolic and Behavioral Compensations in Response to Caloric Restriction: Implications for the Maintenance of Weight Loss PLoS ONE, 4 (2) DOI: 10.1371/journal.pone.0004377

LARSON-MEYER, D., REDMAN, L., HEILBRONN, L., MARTIN, C., & RAVUSSIN, E. (2010). Caloric Restriction with or without Exercise Medicine & Science in Sports & Exercise, 42 (1), 152-159 DOI: 10.1249/MSS.0b013e3181ad7f17

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