Slimming down in old age

See corresponding article on page 279. Obesity in older adults (as in the younger population) has become a major public health problem and presents a serious clinical challenge. It affects ∼30–35% of 65- to 85-y-old US adults and is a major risk factor for cardiometabolic disease (including insulin resistance, nonalcoholic fatty liver disease, low-grade inflammation, dyslipidemia, elevated blood pressure, diabetes, ischemic heart disease, and heart failure) and is associated with frailty and reduced quality of life. Dietary calorie restriction–induced weight loss can improve quality of life and improve or even normalize many of the metabolic abnormalities associated with obesity. Nevertheless, the therapeutic value of weight-loss therapy in obese older adults is controversial and has even been referred to as dangerous by some (1–3) because weight loss decreases both fat mass and lean body (including muscle) mass (4) and could therefore increase the risk of sarcopenia. Weight cycling (due to repeated attempts of losing weight coupled with the inability to keep weight off successfully in the long run), in particular, is considered problematic because it is difficult for older adults to recover muscle mass once lost (5, 6). Moreover, obesity in older adults is not (or is only marginally) associated (7, 8), whereas weight loss is associated (9, 10) with increased mortality risk. However, these results are potentially confounded by “survivors’ bias” and unintentional (illness-related) weight loss. In fact, studies that took into account body composition when evaluating the association between body weight status and mortality reported that all-cause and cardiovascular disease mortality risk is greater in sarcopenic (defined as low muscle mass) and obese individuals than in nonsarcopenic and nonobese persons (11). In addition, both sarcopenia and obesity are associated with an increased risk of falls and mobility disability (12, 13). Therefore, it seems prudent to aim for a reduction in fat mass while preserving muscle mass in obese older adults. The 2 key strategies for maintaining adequate muscle mass and physical functioning in older adults are regular physical activity, particularly resistance exercise, and sufficient dietary protein intake. The PROT-AGE Study Group (14) and the European Society for Parenteral and Enteral Nutrition Expert Group (15) recommend 1.0–1.2 g protein/kg body weight per day and a high dietary leucine content (2.0–2.5 g leucine/d) for older adults. However, the efficacy of this approach is uncertain, and it is unclear if it can prevent the loss of muscle mass during calorie restriction. The results from prospective randomized intervention trials demonstrated that increasing protein intake during exercise training in weight-stable older adults does not result in increased muscle mass or strength (16) and exercise training during calorie restriction in older adults reduces but does not abolish the weight-loss–induced loss of lean body and muscle mass when consuming a “standard” weight-loss diet [i.e., despite participating in a vigorous exercise program, obese older adults lost ∼2–3% of their muscle mass, which is 4 times that of the weight-maintenance control group during the same period and ∼20% of total weight lost (4)]. In this issue of the Journal, Verreijen et al. (17) report the results from a double-blind randomized controlled study designed to evaluate the efficacy of a dietary protein supplement to preserve muscle mass in older adults during intentional weight loss achieved by dietary calorie restriction in combination with resistance exercise training (3 times/wk) for 13 wk. They found that consuming the supplement, which contained 20.7 g leucine-rich whey protein (2.8 g leucine), daily as well as 3 times/wk immediately after the exercise bout resulted in ∼30% greater protein intake in the intervention/supplementation group compared with the control group (1.11 vs. 0.85 g/kg body weight per day, respectively, averaged over 1 wk) and completely abolished the weight-loss–induced loss of muscle mass. These results are remarkable and hold promise, although it needs to be noted that the beneficial effects of protein supplementation on muscle mass were not accompanied by differences in strength and physical functioning, which improved to the same extent in both (standard diet and protein supplement) groups. The intervention was short, and the amount of weight lost was small (only ∼3%); therefore, it remains to be seen whether differences emerge during more marked weight loss and whether the beneficial effect of protein supplementation can be sustained long term. Other intriguing questions are whether the beneficial effect of the dietary supplement in the study by Verreijen et al. (17) was due to its high leucine content, the total amount of protein consumed, or the timing of the supplement immediately after the exercise bout. In weight-stable older adults, leucine-rich whey protein acutely stimulates muscle protein synthesis to a greater extent than do other proteins (18), and Esmarck et al. (19) showed that consuming a 10-g protein supplement immediately after a bout of resistance exercise 3 times/wk led to muscle hypertrophy, whereas consuming the supplement later after exercise did not. The results of the reported study by Verreijen et al. (17) almost certainly are not a consequence of the 1.3 g of fiber and 20 μg of vitamin D3 that were added to the supplement (20). A limitation of the study by Verreijen et al. (17) is the absence of a more comprehensive and balanced assessment of benefits vs. potential risks. Although weight loss and high protein intake within the range achieved in the study by Verreijen et al. (17) are considered safe and do not have clinically significant adverse effects on bone and kidneys (1, 14), it is possible that increased protein intake will have adverse effects on insulin sensitivity of glucose metabolism (21, 22) and increase the risk of diabetes. Carefully designed, long-term weight-loss studies are still needed to define optimal protein/amino acid intake to preserve muscle mass and to achieve metabolic health in obese older adults.