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One of the most consistent benefits of calorie restriction is blood pressure improvements in as short as one or two weeks. Blood pressures can sometimes even be normalized in a matter of weeks, and blood pressure pills discontinued. Unfortunately, this can work a little too well, and cause something called orthostatic intolerance, which can manifest as lightheadedness or dizziness upon standing—which in severe cases can cause fainting. Staying hydrated can help.

What about loss of muscle mass? In the CALERIE trial, 70 percent of the lost body weight was fat, and 30 percent lean body mass. So, they ended up with an improved body composition: 72 percent lean mass, compared to 66 percent in the control group. Though leg muscle mass and strength declined in absolute terms, relative to their new body size, they generally got stronger. Is there any way to preserve even more lean mass, though, particularly among older individuals who naturally tend to lose muscle mass with age?

Increased protein intakes are commonly suggested, but most studies fail to find a beneficial effect on preserving muscle strength or function whether you’re young or old, active or sedentary. For example, researchers randomized overweight older men and women to a normal-protein diet—4 grams for every 10 pounds of body weight, or a high-protein diet—about 8 grams per 10 pounds, during a 25-percent calorie restriction. That doubling of protein intake had no discernible effect on lean body mass, muscle strength, or physical performance. Most such studies found the same lack of benefit. But, put them all together, and one can tease out a small advantage, about a pound or two difference over an average of six months. Unfortunately, high-protein intake during weight loss has been found to have profoundly negative metabolic effects; for example, undermining the benefits of weight loss on insulin sensitivity. Lose 20 pounds, and you can dramatically improve your body’s ability to handle blood sugars, compared to a control group that maintained their weight. Lose the exact same amount of weight, but on a high-protein diet, getting about an extra 30 grams a day, and it’s like you never lost any weight at all.

Though you can always bulk back up after weight loss, the best way to preserve muscle mass during weight loss is exercise. The CALERIE study had no structured exercise component and, like after bariatric surgery, about 30 percent of the weight loss was lean mass. In contrast, that proportion was only about 16 percent in The Biggest Loser contestants, chalked up to their vigorous exercise program. Resistance training even just three times a week can prevent more than 90 percent of lean body mass loss during calorie restriction.

The same may be true of bone loss. Lose weight through calorie restriction alone, and you experience a decline in bone mineral density in fracture risk sites, such as the hip and spine. In the same study, though, those randomized to lose weight with exercise didn’t suffer any bone loss. The researchers conclude: “Our results suggest that regular [exercise] should be included as part of a comprehensive weight loss program to offset the adverse effects of [caloric restriction] on [the] bone.“ You can never argue with calls for increased physical activity, but even without an exercise regimen, the “very small” drop in bone mineral density in the CALERIE trial might only increase a 10-year risk of osteoporotic fracture by only about 0.2 percent. The benefits of calorie restriction revealed by the study—improved blood pressure, improved cholesterol, improved mood, improved libido, improved sleep—would seem to far outweigh any potential risks. The fact that a reduction in calories seemed to have such wide-ranging benefits on quality of life led commentators in the AMA’s Internal Medicine journal to write: “The findings of this well-designed study suggest that intake of excess calories is not only a burden to our physical equilibrium, but also [to] our psychological well-being” as well.

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