Calorie restriction (CR) is an effective method of extending the lifespan of experimental organisms from across the evolutionary spectrum. The method has shown promise in delaying the onset of age-related diseases in humans (specifically atherosclerosis), but human-subject studies are still few and far between.

A recent study addresses the effect of CR on bone loss, and finds that limiting caloric intake can result in decreased bone mineral density (BMD) at clinically relevant sites in the body, i.e., places where fractures often occur in the elderly. Villareal et al.:

Background Bone loss often accompanies weight loss induced by caloric restriction (CR), but whether bone loss accompanies similar weight loss induced by exercise (EX) is unknown. We tested the hypothesis that EX-induced weight loss is associated with less bone loss compared with CR-induced weight loss.

Methods Forty-eight adults (30 women; 18 men; mean ± SD age, 57 ± 3 years; and mean ± SD body mass index, 27 ± 2 kg/m2) were randomized to 1 of 3 groups for 1 year: CR group (n = 19), regular EX group (n = 19), or a healthy lifestyle (HL) control group (n = 10). Primary outcome measure was change in hip and spine bone mineral density (BMD). Secondary outcomes were bone markers and hormones.

Results Body weight decreased similarly in the CR and EX groups (10.7% ± 6.3% [–8.2 ± 4.8 kg] vs 8.4% ± 6.3% [–6.7 ± 5.6 kg]; P = .21), whereas weight did not change in the HL group (–1.2% ± 2.5% [–0.9 ± 2.0 kg]). Compared with the HL group, the CR group had decreases in BMD at the total hip (–2.2% ± 3.1% vs 1.2% ± 2.1%; P = .02) and intertrochanter (–2.1% ± 3.4% vs 1.7 ± 2.8%; P = .03). The CR group had a decrease in spine BMD (–2.2% ± 3.3%; P = .009). Despite weight loss, the EX group did not demonstrate a decrease in BMD at any site. Body weight changes correlated with BMD changes in the CR (R = 0.61; P = .007) but not in the EX group. Bone turnover increased in both CR and EX groups.

Conclusions CR-induced weight loss, but not EX-induced weight loss, is associated with reductions in BMD at clinically important sites of fracture. These data suggest that EX should be an important component of a weight loss program to offset adverse effects of CR on bone.

Inasmuch as BMD loss is a problem even in normal/healthy aging, even when it falls well short of osteoporosis, this is a cause for concern for those considering CR — especially if they begin (like these subjects) in mid-to-late life.

One potential criticism of the research might be that simple calorie restriction without taking special care to maintain optimal nutrition is likely to result in nutritional deficiency. Sifting through the references, however, I found that each subject was in direct and frequent individual consultation with a dietitian, so I don’t think that the BMD loss can be attributed simply to a calcium and protein deficiency syndrome. Still, one wonders whether vitamin supplementation and a very careful eye toward maintaining minimum levels of each micronutrient might have yielded different results.

This is good information to have, of course: As I’ve pointed out before, sometimes very promising anti-aging/pro-longevity regimens can have unforeseen negative consequences, and those considering changing their lifestyle to reap potential benefits should also be aware of potential harms.