Effect of Long-Term Calorie Restriction With Adequate Protein and Micronutrients on Thyroid Hormones
Abstract
CONTEXT: Caloric restriction (CR) retards aging in mammals. It has been hypothesized that a reduction in T(3) hormone may increase life span by conserving energy and reducing free-radical production. OBJECTIVE: The objective of the study was to assess the relationship between long-term CR with adequate protein and micronutrient intake on thyroid function in healthy lean weight-stable adult men and women. DESIGN, SETTING, AND PARTICIPANTS: In this study, serum thyroid hormones were evaluated in 28 men and women (mean age, 52 +/- 12 yr) consuming a CR diet for 3-15 yr (6 +/- 3 yr), 28 age- and sex-matched sedentary (WD), and 28 body fat-matched exercising (EX) subjects who were eating Western diets. MAIN OUTCOME MEASURES: Serum total and free T(4), total and free T(3), reverse T(3), and TSH concentrations were the main outcome measures. RESULTS: Energy intake was lower in the CR group (1779 +/- 355 kcal/d) than the WD (2433 +/- 502 kcal/d) and EX (2811 +/- 711 kcal/d) groups (P < 0.001). Serum T(3) concentration was lower in the CR group than the WD and EX groups (73.6 +/- 22 vs. 91.0 +/- 13 vs. 94.3 +/- 17 ng/dl, respectively) (P < or = 0.001), whereas serum total and free T(4), reverse T(3), and TSH concentrations were similar among groups. CONCLUSIONS: Long-term CR with adequate protein and micronutrient intake in lean and weight-stable healthy humans is associated with a sustained reduction in serum T(3) concentration, similar to that found in CR rodents and monkeys. This effect is likely due to CR itself, rather than to a decrease in body fat mass, and could be involved in slowing the rate of aging.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Apart from lifespan extension, caloric restriction reduces risk factors for major diseases including diabetes and cardiovascular disease in rodents.
“Apart from lifespan extension, caloric restriction also reduces the risk factors for major diseases including diabetes and cardiovascular disease in rodents (209, 210).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [210]
In the Calorie Restriction Society study, those on the calorie-restricted diet demonstrated metabolic improvements including body fat, lower blood pressure, improved insulin sensitivity, and lipid profile.
“Those on the calorie-restricted diet demonstrated a number of metabolic improvements including body fat, lower blood pressure, and improved insulin sensitivity, and lipid profile (210–212).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [210]
Cites
Werner & Ingbar's the thyroid : a fundamental and clinical text
Werner, S. C., Ingbar, S. H., Braverman, L. E., & Utiger, R. D. (2012) · Lippincott-Raven eBooks · Cited by 1,016 · see citing works
Long-Term Calorie Restriction Is Highly Effective in Reducing the Risk for Atherosclerosis in Humans
Fontana, L., Meyer, T. E., Klein, S., & Holloszy, J. O. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308291101 · Cited by 902 · see citing works
Self-citationWeindruch, R. H., & Sohal, R. S. (1997) · New England Journal of Medicine · doi:10.1056/nejm199710023371407 · Cited by 743 · see citing works
Long-term caloric restriction ameliorates the decline in diastolic function in humans
Meyer, T. E., Kovács, S. J., Ehsani, A. A., Klein, S., Holloszy, J. O., & Fontana, L. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.08.069 · Cited by 383 · see citing works
Self-citationEuthyroid Sick Syndrome: Is It a Misnomer?
Chopra, I. J. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.2.3745 · Cited by 374 · see citing works
The Inflammation Hypothesis of Aging: Molecular Modulation by Calorie Restriction
Chung, H. Y., Kim, H. J., Kim, J. W., & Yu, B. P. (2001) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2001.tb05662.x · Cited by 305 · see citing works
Walford, R. L., Mock, D., Verdery, R. B., & MacCallum, T. (2002) · The Journals of Gerontology Series A · doi:10.1093/gerona/57.6.b211 · Cited by 302 · see citing works
EFFECT OF CALORIC RESTRICTION AND DIETARY COMPOSITION ON SERUM T3AND REVERSE T3IN MAN
Spaulding, S. W., CHOPRA, I. J., Sherwin, R. S., & Lyall, S. S. (1976) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-42-1-197 · Cited by 278 · see citing works
Tumor Necrosis Factor: A Putative Mediator of the Sick Euthyroid Syndrome in Man*
POLL, T. V. D., ROMIJN, J. A., WIERSINGA, W. M., & SAUERWEIN, H. P. (1990) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-71-6-1567 · Cited by 270 · see citing works
Kaptein, E. M., Hays, M. T., & Ferguson, D. C. (1994) · Veterinary Clinics of North America Small Animal Practice · doi:10.1016/s0195-5616(94)50051-2 · Cited by 267 · see citing works
Calorie restriction in rhesus monkeys
Mattison, J. A. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(02)00146-8 · Cited by 255 · see citing works
Spaulding, C. C., Walford, R. L., & Effros, R. B. (1997) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(96)01824-6 · Cited by 224 · see citing works
The Nuclear Receptor CAR Is a Regulator of Thyroid Hormone Metabolism during Caloric Restriction
Maglich, J. M., Watson, J. A., McMillen, P. J., Goodwin, B. J., Willson, T. M., & Moore, J. T. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313601200 · Cited by 223 · see citing works
Effects of acute and chronic interleukin-6 administration on thyroid hormone metabolism in humans.
Stouthard, J. M., van der Poll, T., Endert, E., Bakker, P. J., Veenhof, C. H., Sauerwein, H. P., & Romijn, J. A. (1994) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.79.5.7962327 · Cited by 139 · see citing works
Boelen, A., Maas, M. A., Lowik, C. W., Platvoet, M. C., & Wiersinga, W. M. (1996) · Endocrinology · doi:10.1210/endo.137.12.8940342 · Cited by 108 · see citing works
Long-term food restriction depresses serum thyroid hormone concentrations in the rat
Herlihy, J. T., Stacy, C., & Bertrand, H. A. (1990) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(90)90030-j · Cited by 85 · see citing works
Euthyroid Sick Syndrome and the Role of Cytokines
Papanicolaou, D. A. (2000) · Reviews in Endocrine and Metabolic Disorders · doi:10.1023/a:1010060303031 · Cited by 72 · see citing works
Tapia, G., Fernández, V., Varela, P., Cornejo, P., Guerrero, J., & Videla, L. A. (2003) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(03)00209-0 · Cited by 63 · see citing works
Effects of Dietary Caloric Restriction and Aging on Thyroid Hormones of Rhesus Monkeys
Roth, G. S., Handy, A. M., Mattison, J. A., Tilmont, E. M., Ingram, D. K., & Lane, M. A. (2002) · Hormone and Metabolic Research · doi:10.1055/s-2002-33469 · Cited by 58 · see citing works
Pasquali, R., PARENTI, M. A., Mattioli, L., et al. (1982) · Journal of Endocrinological Investigation · doi:10.1007/bf03350482 · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Aging, adiposity, and calorie restriction
Fontana, L. (2007) · JAMA · doi:10.1001/jama.297.9.986 · Cited by 526 · see citing works
Self-citationCalorie restriction in humans: An update
Most, J., Tosti, V., Redman, L. M., & Fontana, L. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.08.005 · Cited by 530 · see citing works
Self-citationRedman, L. M., Smith, S. R., Burton, J. H., Martin, C. K., Il'yasova, D., & Ravussin, E. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.02.019 · Cited by 472 · see citing works
Stekovic, S., Hofer, S. J., Tripolt, N., Aon, M. A., Royer, P., Pein, L., Stadler, J. T., Pendl, T., Prietl, B., Url, J., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.07.016 · Cited by 412 · see citing works
Calorie restriction and cancer prevention: metabolic and molecular mechanisms
Longo, V. D., & Fontana, L. (2010) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2009.11.004 · Cited by 378 · see citing works
Self-citationOf mice and men: the benefits of caloric restriction, exercise, and mimetics
Mercken, E. M., Carboneau, B. A., Krzysik-Walker, S. M., & de Cabo, R. (2012) · Ageing Research Reviews · doi:10.1016/j.arr.2011.11.005 · Cited by 318 · see citing works
Calorie restriction and prevention of age‐associated chronic disease
Omodei, D., & Fontana, L. (2011) · FEBS Letters · doi:10.1016/j.febslet.2011.03.015 · Cited by 293 · see citing works
Self-citationMohammed, I., Hollenberg, M. D., Ding, H., & Triggle, C. R. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.718942 · Cited by 278 · see citing works
Calorie Restriction and Aging in Humans
Flanagan, E. W., Most, J., Mey, J. T., & Redman, L. M. (2020) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-122319-034601 · Cited by 239 · see citing works
Caloric Restriction with or without Exercise: The Fitness versus Fatness Debate
LARSON-MEYER, D. E., REDMAN, L., HEILBRONN, L. K., MARTIN, C. K., & RAVUSSIN, E. (2010) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e3181ad7f17 · Cited by 96 · see citing works
Agnihothri, R. V., Courville, A. B., Linderman, J. D., Smith, S., Brychta, R., Remaley, A., Chen, K. Y., Simchowitz, L., & Celi, F. S. (2014) · Thyroid · doi:10.1089/thy.2013.0055 · Cited by 94 · see citing works
Fontana, L. (2009) · Experimental Gerontology · doi:10.1016/j.exger.2008.04.005 · Cited by 81 · see citing works
Self-citationEndocrine alterations in response to calorie restriction in humans
Redman, L. M., & Ravussin, E. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2008.10.014 · Cited by 54 · see citing works
Nutrition modulation of human aging: The calorie restriction paradigm
Das, S. K., Balasubramanian, P., & Weerasekara, Y. K. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.04.011 · Cited by 51 · see citing works
Influence of calorie reduction on DNA repair capacity of human peripheral blood mononuclear cells
Matt, K., Burger, K., Gebhard, D., & Bergemann, J. (2016) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2016.02.008 · Cited by 17 · see citing works
- Authors
- Fontana, L., Klein, S., Holloszy, J. O., & Premachandra, B. N.
- Affiliations
- Washington University in St. Louis (US)
- Thyroid Specialty Laboratory (B.N.P.), St. Louis, Missouri 63125
- Corresponding author
- Fontana, Luigi
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2006-08-01
- Volume
- 91
- Issue
- 8
- Pages
- 3232-3235
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2071480387
- Cited by
- 149
- References
- 20
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 5 · 2022: 4 · 2021: 6 · 2020: 6 · 2019: 7 · 2018: 7 · 2017: 7 · 2016: 5 · 2015: 5 · 2014: 8 · 2013: 12 · 2012: 6
- FWCI
- 7.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 56351, DK20579, R01DK037948, P30DK056341)
- National Center for Research Resources (M01RR000036)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Keywords
- caloric restriction, thyroid hormones, triiodothyronine, free thyroxine, reverse T3, thyroid-stimulating hormone, protein intake, micronutrient intake, aging, energy intake, fat mass, Western diet, physical activity
- MeSH terms
- Adult, Body Composition, Dietary Proteins, Female, Humans, Male, Middle Aged, Nutritional Physiological Phenomena, Thyroid Hormones, Thyrotropin, Thyroxine, Triiodothyronine, Triiodothyronine, Reverse, Tumor Necrosis Factor-alpha, Exercise, Body Mass Index, Micronutrients, Caloric Restriction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
