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      Low-carbohydrate, high-protein diet score and risk of incident cancer; a prospective cohort study

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          Abstract

          Background

          Although carbohydrate reduction of varying degrees is a popular and controversial dietary trend, potential long-term effects for health, and cancer in specific, are largely unknown.

          Methods

          We studied a previously established low-carbohydrate, high-protein (LCHP) score in relation to the incidence of cancer and specific cancer types in a population-based cohort in northern Sweden. Participants were 62,582 men and women with up to 17.8 years of follow-up (median 9.7), including 3,059 prospective cancer cases. Cox regression analyses were performed for a LCHP score based on the sum of energy-adjusted deciles of carbohydrate (descending) and protein (ascending) intake labeled 1 to 10, with higher scores representing a diet lower in carbohydrates and higher in protein. Important potential confounders were accounted for, and the role of metabolic risk profile, macronutrient quality including saturated fat intake, and adequacy of energy intake reporting was explored.

          Results

          For the lowest to highest LCHP scores, 2 to 20, carbohydrate intakes ranged from median 60.9 to 38.9% of total energy intake. Both protein (primarily animal sources) and particularly fat (both saturated and unsaturated) intakes increased with increasing LCHP scores. LCHP score was not related to cancer risk, except for a non-dose-dependent, positive association for respiratory tract cancer that was statistically significant in men. The multivariate hazard ratio for medium (9–13) versus low (2–8) LCHP scores was 1.84 (95% confidence interval: 1.05-3.23; p-trend = 0.38). Other analyses were largely consistent with the main results, although LCHP score was associated with colorectal cancer risk inversely in women with high saturated fat intakes, and positively in men with higher LCHP scores based on vegetable protein.

          Conclusion

          These largely null results provide important information concerning the long-term safety of moderate carbohydrate reduction and consequent increases in protein and, in this cohort, especially fat intakes. In order to determine the effects of stricter carbohydrate restriction, further studies encompassing a wider range of macronutrient intakes are warranted.

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          Most cited references32

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          Effects of dietary composition on energy expenditure during weight-loss maintenance.

          Reduced energy expenditure following weight loss is thought to contribute to weight gain. However, the effect of dietary composition on energy expenditure during weight-loss maintenance has not been studied. To examine the effects of 3 diets differing widely in macronutrient composition and glycemic load on energy expenditure following weight loss. A controlled 3-way crossover design involving 21 overweight and obese young adults conducted at Children's Hospital Boston and Brigham and Women's Hospital, Boston, Massachusetts, between June 16, 2006, and June 21, 2010, with recruitment by newspaper advertisements and postings. After achieving 10% to 15% weight loss while consuming a run-in diet, participants consumed an isocaloric low-fat diet (60% of energy from carbohydrate, 20% from fat, 20% from protein; high glycemic load), low-glycemic index diet (40% from carbohydrate, 40% from fat, and 20% from protein; moderate glycemic load), and very low-carbohydrate diet (10% from carbohydrate, 60% from fat, and 30% from protein; low glycemic load) in random order, each for 4 weeks. Primary outcome was resting energy expenditure (REE), with secondary outcomes of total energy expenditure (TEE), hormone levels, and metabolic syndrome components. Compared with the pre-weight-loss baseline, the decrease in REE was greatest with the low-fat diet (mean [95% CI], -205 [-265 to -144] kcal/d), intermediate with the low-glycemic index diet (-166 [-227 to -106] kcal/d), and least with the very low-carbohydrate diet (-138 [-198 to -77] kcal/d; overall P = .03; P for trend by glycemic load = .009). The decrease in TEE showed a similar pattern (mean [95% CI], -423 [-606 to -239] kcal/d; -297 [-479 to -115] kcal/d; and -97 [-281 to 86] kcal/d, respectively; overall P = .003; P for trend by glycemic load < .001). Hormone levels and metabolic syndrome components also varied during weight maintenance by diet (leptin, P < .001; 24-hour urinary cortisol, P = .005; indexes of peripheral [P = .02] and hepatic [P = .03] insulin sensitivity; high-density lipoprotein [HDL] cholesterol, P < .001; non-HDL cholesterol, P < .001; triglycerides, P < .001; plasminogen activator inhibitor 1, P for trend = .04; and C-reactive protein, P for trend = .05), but no consistent favorable pattern emerged. Among overweight and obese young adults compared with pre-weight-loss energy expenditure, isocaloric feeding following 10% to 15% weight loss resulted in decreases in REE and TEE that were greatest with the low-fat diet, intermediate with the low-glycemic index diet, and least with the very low-carbohydrate diet. clinicaltrials.gov Identifier: NCT00315354.
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            Low-carbohydrate-diet score and the risk of coronary heart disease in women.

            Low-carbohydrate diets have been advocated for weight loss and to prevent obesity, but the long-term safety of these diets has not been determined. We evaluated data on 82,802 women in the Nurses' Health Study who had completed a validated food-frequency questionnaire. Data from the questionnaire were used to calculate a low-carbohydrate-diet score, which was based on the percentage of energy as carbohydrate, fat, and protein (a higher score reflects a higher intake of fat and protein and a lower intake of carbohydrate). The association between the low-carbohydrate-diet score and the risk of coronary heart disease was examined. During 20 years of follow-up, we documented 1994 new cases of coronary heart disease. After multivariate adjustment, the relative risk of coronary heart disease comparing highest and lowest deciles of the low-carbohydrate-diet score was 0.94 (95% confidence interval [CI], 0.76 to 1.18; P for trend=0.19). The relative risk comparing highest and lowest deciles of a low-carbohydrate-diet score on the basis of the percentage of energy from carbohydrate, animal protein, and animal fat was 0.94 (95% CI, 0.74 to 1.19; P for trend=0.52), whereas the relative risk on the basis of the percentage of energy from intake of carbohydrates, vegetable protein, and vegetable fat was 0.70 (95% CI, 0.56 to 0.88; P for trend=0.002). A higher glycemic load was strongly associated with an increased risk of coronary heart disease (relative risk comparing highest and lowest deciles, 1.90; 95% CI, 1.15 to 3.15; P for trend=0.003). Our findings suggest that diets lower in carbohydrate and higher in protein and fat are not associated with increased risk of coronary heart disease in women. When vegetable sources of fat and protein are chosen, these diets may moderately reduce the risk of coronary heart disease. Copyright 2006 Massachusetts Medical Society.
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              The metabolic syndrome: A high-risk state for cancer?

              The metabolic syndrome is composed of cardiovascular risk factors including increased body mass index/waist circumference, blood pressure, plasma glucose, and triglycerides, as well as decreased high-density lipoprotein cholesterol. The essence of the metabolic syndrome lies in the clustering of these risk factors, which are associated with cardiovascular disease. Interestingly, most of the components of the metabolic syndrome have individually been linked in some way to the development of cancer. However, epidemiological studies linking the metabolic syndrome to cancer are scarce. Nevertheless, two such studies indicate that the clustering of metabolic syndrome components significantly increases the risk of colon cancer mortality compared with the individual components. The purpose of this review is to further explore the potential relationship between the metabolic syndrome and cancer risk. Specifically, we examine the hypothesis that individual components of the metabolic syndrome contribute to the development of several processes, including insulin resistance, aromatase activity, adipokine production, angiogenesis, glucose utilization, and oxidative stress/DNA damage, which can work together to increase cancer risk beyond that of the individual components alone. We propose that the metabolic syndrome be considered as a high-risk state for certain types of cancer and that this relationship should be systematically explored across cancer types.
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                Author and article information

                Contributors
                Journal
                Nutr J
                Nutr J
                Nutrition Journal
                BioMed Central
                1475-2891
                2013
                7 May 2013
                : 12
                : 58
                Affiliations
                [1 ]Department of Public Health and Clinical Medicine,Nutritional Research, Umeå University, Umeå SE-90185, Sweden
                [2 ]Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Göteborg SE-40530, Sweden
                [3 ]Department of Odontology, Umeå University, Umeå SE-90185, Sweden
                [4 ]Department of Public Health and Clinical Medicine, Umeå University, Umeå SE-90185, Sweden
                [5 ]Department of Oncology and Radiation Sciences, Oncological Center, Umeå University, Umeå SE-90185, Sweden
                [6 ]Department of Medical Biosciences, Pathology, Umeå University, Umeå SE-90185, Sweden
                Article
                1475-2891-12-58
                10.1186/1475-2891-12-58
                3654894
                23651548
                d9b4ee00-8ad5-407f-af40-fd722f2d58c4
                Copyright © 2013 Nilsson et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 February 2013
                : 2 May 2013
                Categories
                Research

                Nutrition & Dietetics
                diet,cancer,macronutrients,carbohydrate intake,protein intake,fat intake,cohort study

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