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Caloric restriction alone and with exercise improves CVD risk in healthy non-obese individuals
Open accessAbstract
Unlabelled Calorie restriction (CR) delays the development of age-associated disease and increases lifespan in rodents, but the effects in humans remain uncertain.Purpose Determine the effect of 6 months of CR with or without exercise on cardiovascular disease (CVD) risk factors and estimated 10-year CVD risk in healthy non-obese men and women.Methods Thirty-six individuals were randomized to one of three groups for 6 months: Control, 100% of energy requirements; CR, 25% calorie restriction; CR+EX, 12.5% CR+12.5% increase in energy expenditure via aerobic exercise. CVD risk factors were assessed at baseline, 3 and 6 months.Results After 6 months, CR and CR+EX lost approximately 10% of body weight. CR significantly reduced triacylglycerol (-31+/-15mg/dL) and factor VIIc (-10.7+/-2.3%). Similarly CR+EX reduced triacylglycerol (-22+/-8mg/dL) and additionally reduced LDL-C (-16.0+/-5.1mg/dL) and DBP (-4.0+/-2.1mmHg). In contrast, both triacylglycerol (24+/-14mg/dL) and factor VIIc (7.9+/-2.3%) were increased in the Control group. HDL-cholesterol was increased in all groups while hsCRP was lower in the Controls versus CR+EX. Estimated 10-year CVD risk significantly declined from baseline by 29% in CR (P<0.001) and 38% in the CR+EX (P<0.001) while remaining unchanged in the Control group.Conclusions Based on combined favorable changes in lipid and blood pressure, caloric restriction with or without exercise that induces weight loss favorably reduces risk for CVD even in already healthy non-obese individuals.
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“Similarly, healthy non-obese individuals also improved their cardiovascular risk after six months of calorie restriction as evidenced by a reduction in blood pressure (Lefevre et al., 2009).”
From Calorie Restriction-like Effects of 30 Days of Resveratrol Supplementation on Energy Metabolism and Metabolic Profile in Obese Humans (2011) · cites this paper as Lefevre et al., 2009
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“…support the theory that CR improves markers of disease risk (a decrease in fat mass, and increase in insulin sensitivity) and is consistent with anti-aging effects (Civitarese et al., 2007; Larson-Meyer et al., 2006, 2008; Lefevre et al., 2009; Redman et al., 2008a, 2008b, 2010; Tam et al., 2012).”
BackgroundResultEpigenetic Regulation of Metabolism and Inflammation by Calorie Restriction
Hernández‐Saavedra, D., Moody, L., Xu, G. B., Chen, H., & Pan, Y. (2018) · Advances in Nutrition · doi:10.1093/advances/nmy129 · Cited by 52
Zou, H., Wang, D., Ren, H., Chen, P., Fang, C., Shi, Z., Zhang, P., Wang, J., Wang, J., Cai, K., et al. (2020) · Nutrients · doi:10.3390/nu12030631 · Cited by 51
Huffman, K. M., Redman, L. M., Landerman, L. R., Pieper, C. F., Stevens, R. D., Muehlbauer, M. J., Wenner, B. R., Bain, J. R., Kraus, V. B., Newgard, C. B., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0028190 · Cited by 49
Self-citationAutophagy—A key pathway for cardiac health and longevity
Woodall, B. P., & Gustafsson, Å. B. (2018) · Acta Physiologica · doi:10.1111/apha.13074 · Cited by 50
“In human trials, a relatively modest 25% reduction in calorie intake significantly improved cardiovascular disease risk, as well as mitochondrial function and health.(90,91) While increased autophagy is believed to play a role in these TABLE 1 Summary of autophagy targets and effects”
BackgroundKim, Y., Hwang, J. H., Noh, J., Gang, G., Kim, D. H., Son, H., Kwak, T. H., Shong, M., Lee, I., & Lee, C. (2011) · Cardiovascular Research · doi:10.1093/cvr/cvr110 · Cited by 49
The effects of lifestyle interventions in dynapenic-obese postmenopausal women
Sénéchal, M., Bouchard, D. R., Dionne, I. J., & Brochu, M. (2012) · Menopause · doi:10.1097/gme.0b013e318248f50f · Cited by 48
“Previous data have shown that HDL cholesterol tends to decrease during the active phase of weight loss and increase after body weight stabilization.(66) To our knowledge, only one other study has investigated the impact of a lifestyle intervention on the metabolic profile of dynapenic postmenopausal women.”
ResultNutrimiRAging: Micromanaging Nutrient Sensing Pathways through Nutrition to Promote Healthy Aging
Micó, V., Berninches, L., Tapia, J., & Daimiel, L. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18050915 · Cited by 50
“Further studies of the Pennington CALERIE Team have shown that CR reduces liver lipid content [34] and improves CVD risk [35].”
BackgroundSherwood, N. E., Crain, A. L., Martinson, B. C., Anderson, C. P., Hayes, M. G., Anderson, J. D., Senso, M. M., & Jeffery, R. W. (2012) · Preventive Medicine · doi:10.1016/j.ypmed.2012.12.014 · Cited by 50
“(Lefevre et al., 2009; Wing et al., 2011) Moreover, Self-Directed participants received similar intervention content (i.e., Keep It Off workbook) and participated in two phone coaching calls.”
Backgroundvan Ginhoven, T. V., Mitchell, J., Verweij, M., Hoeijmakers, J., Ijzermans, J. N., & de Bruin, R. W. D. (2009) · Liver transplantation · doi:10.1002/lt.21871 · Cited by 38
What is the best diet for cardiovascular wellness? A comparison of different nutritional models
Migliaccio, S., Brasacchio, C., Pivari, F., Salzano, C., Barrea, L., Muscogiuri, G., Savastano, S., Colao, A., & on behalf of Obesity Programs of nutrition, E. (2020) · International Journal of Obesity Supplements · doi:10.1038/s41367-020-0018-0 · Cited by 39
Role of dietary modifications in the management of type 2 diabetic complications
Oza, M. J., Laddha, A. P., Gaikwad, A. B., Mulay, S. R., & Kulkarni, Y. A. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105602 · Cited by 42
Koschei the immortal and anti-aging drugs
Blagosklonny, M. V. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.520 · Cited by 41
Caloric restriction mimetics for the treatment of cardiovascular diseases
Sciarretta, S., Forte, M., Castoldi, F., Frati, G., Versaci, F., Sadoshima, J., Kroemer, G., & Maiuri, M. C. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvaa297 · Cited by 39
Patterns of Compensatory Behaviors and Disordered Eating in College Students
Schaumberg, K., Anderson, L. M., Reilly, E. E., & Anderson, D. A. (2014) · Journal of American College Health · doi:10.1080/07448481.2014.930468 · Cited by 38
“Exercise differs from other compensatory behaviors, such as vomiting and laxative use, as moderate amounts of exercise are generally considered part of a healthy lifestyle.(18) Exercise is recommended to maintain physical health,(19) and is associated with positive mental health outcomes.”
BackgroundYu, W., Qin, J., Chen, C., Fu, Y., & Wang, W. (2018) · Molecular Medicine Reports · doi:10.3892/mmr.2018.9390 · Cited by 37
Histone Deacetylase SIRT1, Smooth Muscle Cell Function, and Vascular Diseases
Wang, F., & Chen, H. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.537519 · Cited by 40
Khalafi, M., Sakhaei, M. H., Kazeminasab, F., Rosenkranz, S. K., & Symonds, M. E. (2023) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2023.05.024 · Cited by 45
Age-related cardiovascular disease and the beneficial effects of calorie restriction
Sung, M. M. Y., & Dyck, J. R. B. (2011) · Heart Failure Reviews · doi:10.1007/s10741-011-9293-8 · Cited by 38
Dietary restriction: could it be considered as speed bump on tumor progression road?
Cangemi, A. G., Fanale, D., Rinaldi, G., Bazan, V., Galvano, A., Perez, A., Barraco, N., Massihnia, D., Castiglia, M., Vieni, S., et al. (2016) · Tumor Biology · doi:10.1007/s13277-016-5044-8 · Cited by 37
Nutrition, metabolism, and targeting aging in nonhuman primates
Balasubramanian, P., Mattison, J. A., & Anderson, R. M. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.02.002 · Cited by 36
Marlatt, K. L., Redman, L. M., Burton, J. H., Martin, C. K., & Ravussin, É. (2017) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.116.146837 · Cited by 37
Self-citationMa, L., Wang, R., Wang, H., Zhang, Y., & Zhao, Z. (2020) · Food & Nutrition Research · doi:10.29219/fnr.v64.3668 · Cited by 37
“Studies have established that CR can improve insulin sensitivity, and reduce cardiovascular risk by controlling cardiovascular risk factors (12); however, its specific biological basis remains uncertain.”
BackgroundInnovations in Geroscience to enhance mobility in older adults
Anton, S. D., Cruz‐Almeida, Y., Singh, A., Alpert, J. M., Bensadon, B. A., Cabrera, M., Clark, D. J., Ebner, N. C., Esser, K. A., Fillingim, R. B., et al. (2020) · Experimental Gerontology · doi:10.1016/j.exger.2020.111123 · Cited by 40
Kebbe, M., Sparks, J. R., Flanagan, E. W., & Redman, L. M. (2021) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2021.1922077 · Cited by 39
Self-citationEndothelial Regenerative Capacity and Aging: Influence of Diet, Exercise and Obesity
Ross, M. (2018) · Current Cardiology Reviews · doi:10.2174/1573403x14666180726112303 · Cited by 33
“Such diets have been proven to be beneficial for weight loss in overweight and obese individuals [155, 156] due to the stark effects on reducing oxidative stress [157] and improving the metabolic profile of obese and older humans [156, 158-160].”
BackgroundStroeve, J. H. M., Saccenti, E., Bouwman, J., Dane, A. D., Strassburg, K., Vervoort, J. J. M., Hankemeier, T., Astrup, A. V., Smilde, A. K., van Ommen, B., et al. (2016) · Obesity · doi:10.1002/oby.21361 · Cited by 33
“In addition, the plasma lipid profile improves; plasma triacylglycerols and low-density cholesterol particles reduce while the level of circulating high-density cholesterol particles increases (5,7,8).”
BackgroundAging, neurogenesis, and caloric restriction in different model organisms.
Arslan-Ergül, A., Ozdemir, A. T., & Adams, M. M. (2013) · Europe PMC (PubMed Central) · Cited by 32
Eriau, E., Paillet, J., Kroemer, G., & Pol, J. G. (2021) · Cancers · doi:10.3390/cancers13061260 · Cited by 31
“These effects translated to a 30% reduction of the 10-year risk of cardiovascular disease [54], confirming earlier projections [60].”
BackgroundThe Panacea of Human Aging: Calorie Restriction Versus Exercise
Broskey, N. T., Marlatt, K. L., Most, J., Erickson, M. L., Irving, B. A., & Redman, L. M. (2019) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000193 · Cited by 35
“Collectively, these improvements lower the 10-yr risk for cardiovascular mortality (24,25) and risk for developing type 2 diabetes.”
BackgroundMethodSelf-citation
Metadata
- Authors
- Lefevre, M., Redman, L. M., Heilbronn, L. K., Smith, J. V., Martin, C. K., Rood, J. C., Greenway, F. L., Williamson, D. A., Smith, S. R., & Ravussin, E.
- Affiliations
- Utah State University (US)
- Pennington Biomedical Research Center (US)
- Garvan Institute of Medical Research (AU)
- William Carey University (US)
- ORCID
- Venue
- Atherosclerosis
- Publisher
- Elsevier BV
- Published
- 2009-03
- Volume
- 203
- Issue
- 1
- Pages
- 206-213
- ISSN
- 0021-9150 (ISSN-L)
- PMC
- PMC2692631
- OpenAlex
- W2067805867
- Cited by
- 217
- References
- 39
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 10 · 2023: 7 · 2022: 12 · 2021: 11 · 2020: 19 · 2019: 12 · 2018: 12 · 2017: 11 · 2016: 12 · 2015: 8 · 2014: 16 · 2013: 15 · 2012: 15
- FWCI
- 11.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Atherosclerosis (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- National Institutes of Health (5k23dk068052-04)
- National Institute on Aging (U01AG020478, U01-AG20478)
- National Institute of Diabetes and Digestive and Kidney Diseases (1K23 DK 068052-01A2, P30DK072476)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Dietary Effects on Health
- Health Sciences › Medicine › Physiology (medical) › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Physical Activity and Health
- Keywords
- caloric restriction, aerobic exercise, cardiovascular risk, non-obese adults, weight loss, triglycerides, LDL cholesterol, HDL cholesterol, C-reactive protein, blood pressure, lipid profile
- MeSH terms
- Adult, Age Factors, Aging, Body Weight, Cardiovascular Diseases, Female, Humans, Male, Middle Aged, Obesity, Risk Factors, Exercise, Caloric Restriction, Overweight, Nutritional Sciences
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