M, Male; F, female; ns, not significant; hsCRP, high-sensitivity CRP. Participants recorded all food and beverage intake for 7 consecutive days. Food records were analyzed by using the Nutrition Data System from the Nutrition Coordinating Center of the University of Minnesota version 4.

Serum T 4 concentrations were determined by using fluorescence polarization immunoassay. Serum T 3 , TSH, free T 3 , and free T 4 FT4 concentrations were determined by using microparticle enzyme immunoassay Abbott Laboratories, North Chicago, IL. Serum rT 3 concentrations were determined by using RIA Quest Diagnostics Nichols Institute, San Juan Capistrano, CA.

One-way ANOVA was used to compare group variables, followed by Tukey post hoc testing when indicated. One-way ANOVA with Games-Howell was performed for distributions in which equal variances could not be assumed. All data were analyzed by using SPSS software version All values are expressed as means ± sd.

Mean body mass index BMI values were different among the three groups Table 1. Total body fat and truncal fat were similar in the CR and EX groups and lower than in the WD group Table 2. Foods with a high nutrient to energy ratio such as vegetables, fruits, nuts, dairy products, egg whites, wheat and soy proteins, and meat were consumed, whereas processed foods, rich in refined carbohydrates, free sugars, and partially hydrogenated oils, were avoided.

Mean serum T 3 concentration was significantly lower in the CR group than the EX or WD groups, whereas serum T 4 and FT4, and TSH concentrations were not significantly different among groups Table 1.

Mean serum free T 3 concentration normal range 1. Mean serum TNFα concentration was lower in the CR group than in the EX and WD groups, and mean serum CRP concentration was lower in the CR group than in the WD group Table 1.

Mean serum albumin concentration was similar in the CR 4. Mean serum prealbumin concentration in 10 CR subjects who had the lowest serum total T 3 concentrations was not significantly different from 10 age- and sex-matched sedentary WD subjects The effect of long-term CR with adequate protein and micronutrient intake on thyroid function has not been carefully evaluated in healthy lean, weight-stable subjects.

We found that serum T 3 concentrations were lower in the CR group than sedentary or exercising subjects eating a WD. In contrast, no significant differences in serum TSH, T 4 , FT4, or rT 3 were detected between groups.

Our data suggest that the mechanism responsible for the decrease in serum T 3 concentrations induced by CR is likely related to CR itself, rather than changes in body composition. It has been hypothesized that energy deprivation can modulate serum T 3 concentration by reducing the activity or concentrations of iodothyronine deiodinases, which convert T 4 to T 3 6.

Data from a series of studies have shown that short-term 2 wk to 6 months fasting or severe CR decreases serum T 3 and transiently increases serum rT 3 concentrations in obese subjects who are actively losing weight 9.

Therefore, our findings provide evidence that long-term CR in sedentary lean, weight-stable subjects causes similar but persistent changes in thyroid hormones as previously reported during short-term fasting or CR in obese subjects who were continuing to experience active diet-induced weight loss.

Patients who have the sick euthyroid syndrome also have low serum T 3 concentrations However, these patients have systemic nonthyroidal illnesses, such as cancer, myocardial infarction, severe infections, and major injuries 6 , Therefore, it is likely that inflammation, rather than decreased calorie intake, is responsible for the reduction in serum T 3 concentrations in patients with sick euthyroid syndrome In fact, infusion of proinflammatory cytokines in human subjects decreases serum T 3 concentration 14 , Moreover, the decline in serum T 3 concentration induced by illness is blunted in IL-6 knockout mice, which supports the notion that cytokines are involved in the pathogenesis of the sick euthyroid syndrome In contrast, low serum T 3 concentration was not associated with an increase in inflammatory cytokines in our CR subjects.

In fact, markers of systemic inflammation, serum CRP and TNFα concentrations, were low in our CR subjects. These findings are consistent with data from CR studies conducted in rodents and monkeys, which showed that CR caused a marked decrease in markers of inflammation and a reduction in serum T 3 concentration 7 , 8 , 17 , The combination of decreased serum T 3 and reduced systemic inflammation could alter the aging process by reducing metabolic rate, oxidative stress, and systemic inflammation 1 , 19 , In conclusion, the results of this study demonstrate that long-term CR, with adequate intake of protein and micronutrients, in healthy lean and weight-stable subjects is associated with sustained low serum T 3 concentration, similar to that found in calorie-restricted rodents and monkeys.

This effect is likely due to CR itself, rather than a decrease in body fat mass, and could be involved in slowing the rate of aging. participated in the concept, design, and implementation of the study, undertook plausibility testing, and drafted the report.

participated in the design and drafting of the report. participated in the concept, design, and implementation of the study and drafting of the report. participated in the design and implementation of the study and drafting of the report.

All the authors declared that they participated in the study as mentioned above and that they reviewed and approved the manuscript in its final version. This research was supported by General Clinical Research Center Grant MO1 RR, Diabetes Research and Training Center Grant DK, Clinical Nutrition Research Unit Grant DK, and National Institutes of Health Grant RO1 DK The authors declare that they have no conflict of interest in connection with this paper.

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Download references. We hereby acknowledge the PhD grant provided by the University of the Balearic Islands. Sport Nutrition and Physiology Dept, Olympic Training Center, CAR — GIRSANE, Sant Cugat del Vallés, Spain. Research Group on Community Nutrition and Oxidative Stress, Science Laboratory of Physical Activity, Department of Fundamental Biology and Health Sciences, University of Balearic Islands, , Palma de Mallorca, Spain.

Xavier Capó, Miquel Martorell, Antoni Sureda, Josep A. Xavier Capó, Antoni Sureda, Josep A. Departamento de Nutrición y Dietética, Facultad de Farmacia, Universidad de Concepción, , Concepción, Chile.

You can also search for this author in PubMed Google Scholar. VP, JR, XC, MM, AS, JAT, FD and AP conception and design of research; VP, JR, XC, and MM, performed experiments; VP, JR, XC, MM, AS and FD analysed data; VP and MM interpreted results of experiments; VP, JR, MM drafted manuscript; JR, AS, MM, JAT, FD and AP edited and revised manuscript; JR, XC, MM, AS, FD, JAT, and AP approved final version of manuscript.

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Open Access This article is distributed under the terms of the Creative Commons Attribution 4. Reprints and permissions. Pons, V. et al. Calorie restriction regime enhances physical performance of trained athletes.

J Int Soc Sports Nutr 15 , 12 If the resting metabolic rate is higher on average, more energy is used to perform any cellular functions, including during physical activity, digestion, and storage of energy substrates i.

A chronically high resting metabolic rate is a sign of mitochondrial inefficiency [4] , which typically lends itself to problematic energy production and utilization in the long run.

Oxidative Stress, Aging, and Metabolic Efficiency. The rate of living theory is connected to many other theories of aging pertaining to mitochondrial oxidative stress. The resting metabolic rate can increase the level of oxidation that occurs as well as the degree of free radicals produced as a result.

Over time and with aging, more energy is expended, more damage to cells can accumulate, and regulatory antioxidant mechanisms become less functional. Healthy, aged individuals are known to have a lower resting metabolic rate, which is a possible compensation for diminished cellular functions after a lifetime of oxidative stress accumulation.

Disease and Metabolic Rate. Secondary aging as a result of disease or life stressors impacts cellular function in a similar way to that of ordinary aging. Initially, they serve to increase resting metabolic rate, oxidative stress levels, and free radical production. In the later terminal stages of the disease, the resting metabolic rate slows down and is comparable to that of advanced aging.

Factors Influencing RMR. Resting metabolic rate can be increased by many factors, including:. Balanced Caloric Restriction Promotes Efficient Energy Production.

Restricting calories lowers the supply of substrates for energy production, which eventually reduces the rate at which energy is produced and used at rest. A lower RMR in this context eventually promotes more efficient cellular energy production, which facilitates a better regulation of oxidative stress, lower free radical damage, and potentially, a slower aging process.

Reduced Calorie Intake Positively Redistributes Energy Expenditure. Caloric restriction promotes both a reduction in and a redistribution of energy expenditure. While overall energy requirements eventually reduce, less energy is also spent on digestion due to a lower intake of calories, which frees up more energy for physical activity.

Caloric restriction has been studied in the context of historical food restriction, long-term trials, and animal studies, all of which have shown promising effects with respect to aging and metabolic health. There does not seem to be a caloric restriction method that poses more benefit over another method.

Thus, the best method depends on the needs of the individual. The Difference Appears Minimal Between Time-Restricted Eating and Caloric Restriction. In a small-scale trial on participants, the differences between caloric restriction achieved either through dietary calorie control or time-restricted eating were minimal.

Participants who limited consumption between 8 am and 4 pm lost 8kg on average over the course of a year, whereas those who limited their calorie intake lost 6. All other health outcomes were similarly beneficial. When the timing of food is accounted for, the differences in the above results are negligible.

Short-Term Fasting and Caloric Restriction Benefits Proved Similar. Fasting on alternate days zero calories for days; normal consumption every other day proved to promote the same benefit as a continuous caloric restriction in young to middle-aged adults.

Despite this difference, there was no compensation in eating habits once normal consumption resumed in alternate day fasting. Intermittent Fasting or Time-Restricted Eating Can Be Easier to Implement. Despite these findings, precise caloric restriction is often more difficult to implement safely than time-restricted eating or intermittent fasting.

Most people are not prepared to measure their nutrient intake or count their calories, and the process is prone to miscalculation. Long-Term Consistency Promotes Better Metabolic Stability. While the results are comparable across studies for different types of caloric restriction diets, consistency is vital for reaping the long-term benefits.

In trials that lowered metabolic rate, it has been observed that participants often compensated behaviorally by engaging in less physical activity. After years, the metabolism eventually stabilized, and participants were engaging in their usual activity levels while consuming fewer calories.