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The Influence of n-3PUFA Supplementation on Muscle Strength, Mass, and Function: A Systematic Review and Meta-Analysis.
Santo André, HC, Esteves, GP, Barreto, GHC, Longhini, F, Dolan, E, Benatti, FB
Advances in nutrition (Bethesda, Md.). 2023;14(1):115-127
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Omega 3 polyunsaturated fatty acids (n-3PUFA) are long-chain polyunsaturated fatty acids essential to human health. They play a role in cell membrane integrity, immune and inflammation regulation, cognition and neuromuscular function. As the human body cannot make these fatty acids, they need to be obtained through diet or supplementation. Regarding skeletal muscle, recent research showed that n-3PUFAs may increase the uptake of amino acids by increasing the membrane fluidity in the muscle, and by activating pathways that inhibit protein breakdown. This led to the hypothesis that n-3PUFAs may enhance muscle mass gain and strength. This systematic review sought to gather all available evidence about the impact of n-3PUFA supplementation on muscle mass, strength, and function in healthy young and older adults. The review included 14 studies with a total of 1443 participants. The authors found that n-3PUFA supplementation had no significant effect on muscle mass or muscle function in healthy young and older adults, however, a very small but significant positive effect was noted regarding muscle strength. In the discussion section, the authors explain the challenges of their review and how these findings integrate with the current understanding and other research findings. They concluded more research is needed to get a better insight into the effects of n-3PUFA on muscle function and the variants.
Abstract
The effects of omega 3 polyunsaturated fatty acids (n-3PUFA) supplementation on skeletal muscle are currently unclear. The purpose of this systematic review was to synthesize all available evidence regarding the influence of n-3PUFA supplementation on muscle mass, strength, and function in healthy young and older adults. Four databases were searched (Medline, Embase, Cochrane CENTRAL, and SportDiscus). Predefined eligibility criteria were determined according to Population, Intervention, Comparator, Outcomes, and Study Design. Only peer-reviewed studies were included. The Cochrane RoB2 Tool and the NutriGrade approach were used to access risk of bias and certainty in evidence. Effect sizes were calculated using pre-post scores and analyzed using a three-level, random-effects meta-analysis. When sufficient studies were available, subanalyses were performed in the muscle mass, strength, and function outcomes according to participant's age (<60 or ≥60 years), supplementation dosage (<2 or ≥2 g/day), and training intervention ("resistance training" vs. "none or other"). Overall, 14 individual studies were included, total 1443 participants (913 females; 520 males) and 52 outcomes measures. Studies had high overall risk of bias and consideration of all NutriGrade elements resulted in a certainty assessment of moderate meta-evidence for all outcomes. n-3PUFA supplementation had no significant effect on muscle mass (standard mean difference [SMD] = 0.07 [95% CI: -0.02, 0.17], P = 0.11) and muscle function (SMD = 0.03 [95% CI: -0.09, 0.15], P = 0.58), but it showed a very small albeit significant positive effect on muscle strength (SMD = 0.12 [95% CI: 0.006, 0.24], P = 0.04) in participants when compared with placebo. Subgroup analyses showed that age, supplementation dose, or cosupplementation alongside resistance training did not influence these responses. In conclusion, our analyses indicated that n-3PUFA supplementation may lead to very small increases in muscle strength but did not impact muscle mass and function in healthy young and older adults. To our knowledge, this is the first review and meta-analysis investigating whether n-3PUFA supplementation can lead to increases in muscle strength, mass, and function in healthy adults. Registered protocol: doi.org/10.17605/OSF.IO/2FWQT.
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High-protein diets and testosterone.
Whittaker, J
Nutrition and health. 2023;29(2):185-191
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High protein diets have been shown to have several benefits such as weight loss and the promotion of feeling fuller for longer following food. A recent study has however shown that testosterone levels are decreased in men who follow a high protein diet. This study aimed to summarise the data on high protein diets and testosterone. The results showed that diets with more than 3.4g/kg/day protein decreased total testosterone levels possibly due to the body adjusting its biochemistry to ensure that the excess protein in the diet is metabolised. Furthermore, inflammation in response to an increased amount of protein may suppress testosterone production. It was concluded that increased protein intake of more than 3.4g/kg/day drives the decrease in total testosterone in the body of men regardless of what happens to the level of carbohydrate and fat in the body. This study could be used by healthcare professionals to understand that high protein diets may decrease testosterone levels in men.
Abstract
A recent meta-analysis found low-carbohydrate, high-protein diets (> 3.4 g/kg of bodyweight/day) (g/kg/day) decreased men's total testosterone (∼5.23 nmol/L) [Whittaker and Harris (2022) Low-carbohydrate diets and men's cortisol and testosterone: systematic review and meta-analysis. Nutrition and Health. DOI: 10.1177/02601060221083079]. This finding has generated substantial discussion, however, it has often lacked clarity and context, with the term 'high-protein' being used unqualified. Firstly, diets < 3.4 g/kg/day are not associated with a consistent decrease in testosterone. Secondly, the average protein intake is ∼1.3 g/kg/day, conventional 'high-protein' diets are ∼1.8-3 g/kg/day and the vast majority of athletes are < 3.4 g/kg/day; meaning very few individuals will ever surpass 3.4 g/kg/day. To avoid such confusion in the future, the following definitions are proposed: very high (> 3.4 g/kg/day), high (1.9-3.4 g/kg/day), moderate (1.25-1.9 g/kg/day) and low (<1.25 g/kg/day). Using these, very high-protein diets (> 3.4 g/kg/day) appear to decrease testosterone, however high- and moderate-protein diets (1.25-3.4 g/kg/day) do not.
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Sugar-sweetened beverages, low/no-calorie beverages, fruit juice and non-alcoholic fatty liver disease defined by fatty liver index: the SWEET project.
Naomi, ND, Ngo, J, Brouwer-Brolsma, EM, Buso, MEC, Soedamah-Muthu, SS, Pérez-Rodrigo, C, Harrold, JA, Halford, JCG, Raben, A, Geleijnse, JM, et al
Nutrition & diabetes. 2023;13(1):6
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Non-alcoholic fatty liver disease (NAFLD) refers to a broad range of liver disorders and the major determinants of NAFLD include sedentary lifestyles and poor-quality diets, namely high sugar intake. The main aim of this study was to investigate the association between sugar-sweetened beverages (SSB), low/no-calorie beverages (LNCB), and fruit juice (FJ) intakes and fatty liver index (FLI)-defined NAFLD. This study represents harmonised data of four European studies; Lifelines Cohort study, the Nutrition Questionnaire Plus study, the PREDIMED-Plus study, and the Alpha Omega Cohort. Results showed adverse associations between SSB and LNCB intakes and FLI-defined NAFLD prevalence, as well as between replacement of SSB with the same amount of LNCB and FLI-defined NAFLD. Furthermore, there was a beneficial association between moderate intake of FJ and FLI-defined NAFLD at intake level of ≤2 servings/day when compared to no intake. Authors conclude that long-term prospective studies with objective methods determining the intake of sugar and sweeteners are warranted to further substantiate the findings of their study.
Abstract
BACKGROUND Sweetened beverage intake may play a role in non-alcoholic fatty liver disease (NAFLD) development, but scientific evidence on their role is limited. This study examined associations between sugar-sweetened beverages (SSB), low/no-calorie beverages (LNCB) and fruit juice (FJ) intakes and NAFLD in four European studies. METHODS Data for 42,024 participants of Lifelines Cohort, NQPlus, PREDIMED-Plus and Alpha Omega Cohort were cross-sectionally analysed. NAFLD was assessed using Fatty Liver Index (FLI) (≥60). Restricted cubic spline analyses were used to visualize dose-response associations in Lifelines Cohort. Cox proportional hazard regression analyses with robust variance were performed for associations in individual cohorts; data were pooled using random effects meta-analysis. Models were adjusted for demographic, lifestyle, and other dietary factors. RESULTS Each additional serving of SSB per day was associated with a 7% higher FLI-defined NAFLD prevalence (95%CI 1.03-1.11). For LNCB, restricted cubic spline analysis showed a nonlinear association with FLI-defined NAFLD, with the association getting stronger when consuming ≤1 serving/day and levelling off at higher intake levels. Pooled Cox analysis showed that intake of >2 LNCB servings/week was positively associated with FLI-defined NAFLD (PR 1.38, 95% CI 1.15-1.61; reference: non-consumers). An inverse association was observed for FJ intake of ≤2 servings/week (PR 0.92, 95% CI: 0.88-0.97; reference: non-consumers), but not at higher intake levels. Theoretical replacement of SSB with FJ showed no significant association with FLI-defined NAFLD prevalence (PR 0.97, 95% CI 0.95-1.00), whereas an adverse association was observed when SSB was replaced with LNCB (PR 1.12, 95% CI 1.03-1.21). CONCLUSIONS Pooling results of this study showed that SSB and LNCB were positively associated with FLI-defined NAFLD prevalence. Theoretical replacement of SSB with LNCB was associated with higher FLI-defined NAFLD prevalence. An inverse association was observed between moderate intake of FJ and FLI-defined NAFLD. Our results should be interpreted with caution as reverse causality cannot be ruled out.
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Association Between Omega-3 Fatty Acid Intake and Dyslipidemia: A Continuous Dose-Response Meta-Analysis of Randomized Controlled Trials.
Wang, T, Zhang, X, Zhou, N, Shen, Y, Li, B, Chen, BE, Li, X
Journal of the American Heart Association. 2023;12(11):e029512
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Dyslipidaemia is considered to be a risk factor for cardiovascular disease (CVD) and the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are thought to confer benefits for both dyslipidaemia and CVD, although results from clinical trials and meta-analyses (studies pooling data from smaller studies to increase statistical power) are mixed. The aim of this meta-analysis, using a particular statistical method, was to evaluate whether dose-response relationships may be non-linear. This meta-analysis included 90 randomised controlled trials with 72,598 participants overall. Lipids evaluated were triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and non-HDL cholesterol. A near linear relationship was seen between intake of combined EPA and DHA and a decrease in TG and non-HDL, both overall and for the subgroups of patients with and without hyperlipidaemia and overweight. For LDL and HDL, J-shaped relationships were seen, with an increase followed by a decrease with increasing EPA + DHA intake, both overall and in the subgroups with and without hyperlipidaemia. The authors also pooled data from studies which used the red blood cell omega index (a measure of omega-3 status) and found that with increasing omega-3 status, TG and non-HDL declined whilst HDL increased in a near linear fashion, whilst there was still a J-shaped curve for LDL. The authors consider that a medium dose of EPA + DHA may be needed for the management of dyslipidaemia, and a high dose for people at high risk of developing CVD.
Abstract
Background Previous results provide supportive but not conclusive evidence for the use of omega-3 fatty acids to reduce blood lipids and prevent events of atherosclerotic cardiovascular disease, but the strength and shape of dose-response relationships remain elusive. Methods and Results This study included 90 randomized controlled trials, reported an overall sample size of 72 598 participants, and examined the association between omega-3 fatty acid (docosahexaenoic acid, eicosapentaenoic acid, or both) intake and blood lipid changes. Random-effects 1-stage cubic spline regression models were used to study the mean dose-response association between daily omega-3 fatty acid intake and changes in blood lipids. Nonlinear associations were found in general and in most subgroups, depicted as J-shaped dose-response curves for low-/high-density lipoprotein cholesterol. However, we found evidence of an approximately linear dose-response relationship for triglyceride and non-high-density lipoprotein cholesterol among the general population and more evidently in populations with hyperlipidemia and overweight/obesity who were given medium to high doses (>2 g/d). Conclusions This dose-response meta-analysis demonstrates that combined intake of omega-3 fatty acids near linearly lowers triglyceride and non-high-density lipoprotein cholesterol. Triglyceride-lowering effects might provide supportive evidence for omega-3 fatty acid intake to prevent cardiovascular events.
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An updated systematic review and meta-analysis on adherence to mediterranean diet and risk of cancer.
Morze, J, Danielewicz, A, Przybyłowicz, K, Zeng, H, Hoffmann, G, Schwingshackl, L
European journal of nutrition. 2021;60(3):1561-1586
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The development of cancer is associated with a number of risk factors, including smoking, obesity, sedentary lifestyles, alcohol consumption, infections, pollution, and dietary imbalances. Based on previous research, optimal consumption of fruits, vegetables, and whole grains, along with reduced consumption of red and processed meat, reduces cancer risk. According to this systematic review and meta-analysis, adherence to the Mediterranean diet is associated with lower cancer mortality and site-specific cancer development. A Mediterranean diet includes fruits, vegetables, nuts, legumes, fish, whole grains, extra virgin olive oil, and low amounts of red meat, processed meat, egg, and dairy, along with moderate amounts of red wine. According to this systematic review and meta-analysis, adherence to the Mediterranean diet reduces the risk of cancer mortality and the risk of developing cancers specific to the site, such as colorectal cancer, bladder cancer, gastric cancer, and lung cancer. Among the components of the Mediterranean diet, fruits, vegetables, and whole grains have been shown to reduce cancer risk. Bioactive substances found in Mediterranean diet components require additional robust studies to evaluate their benefits. A healthcare professional can use the results of this study to make clinical decisions and recommend therapeutic interventions to cancer patients.
Abstract
PURPOSE The aim of current systematic review was to update the body of evidence on associations between adherence to the Mediterranean diet (MedDiet) and risk of cancer mortality, site-specific cancer in the general population; all-cause, and cancer mortality as well as cancer reoccurrence among cancer survivors. METHODS A literature search for randomized controlled trials (RCTs), case-control and cohort studies published up to April 2020 was performed using PubMed and Scopus. Study-specific risk estimates for the highest versus lowest adherence to the MedDiet category were pooled using random-effects meta-analyses. Certainty of evidence from cohort studies and RCTs was evaluated using the NutriGrade scoring system. RESULTS The updated search revealed 44 studies not identified in the previous review. Altogether, 117 studies including 3,202,496 participants were enclosed for meta-analysis. The highest adherence to MedDiet was inversely associated with cancer mortality (RRcohort: 0.87, 95% CI 0.82, 0.92; N = 18 studies), all-cause mortality among cancer survivors (RRcohort: 0.75, 95% CI 0.66, 0.86; N = 8), breast (RRobservational: 0.94, 95% CI 0.90, 0.97; N = 23), colorectal (RRobservational: 0.83, 95% CI 0.76, 0.90; N = 17), head and neck (RRobservational: 0.56, 95% CI 0.44, 0.72; N = 9), respiratory (RRcohort: 0.84, 95% CI 0.76, 0.94; N = 5), gastric (RRobservational: 0.70, 95% CI 0.61, 0.80; N = 7), bladder (RRobservational: 0.87, 95% CI 0.76, 0.98; N = 4), and liver cancer (RRobservational: 0.64, 95% CI 0.54, 0.75; N = 4). Adhering to MedDiet did not modify risk of blood, esophageal, pancreatic and prostate cancer risk. CONCLUSION In conclusion, our results suggest that highest adherence to the MedDiet was related to lower risk of cancer mortality in the general population, and all-cause mortality among cancer survivors as well as colorectal, head and neck, respiratory, gastric, liver and bladder cancer risks. Moderate certainty of evidence from cohort studies suggest an inverse association for cancer mortality and colorectal cancer, but most of the comparisons were rated as low or very low certainty of evidence.
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Effect of dietary nitrate on human muscle power: a systematic review and individual participant data meta-analysis.
Coggan, AR, Baranauskas, MN, Hinrichs, RJ, Liu, Z, Carter, SJ
Journal of the International Society of Sports Nutrition. 2021;18(1):66
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Previous reviews have concluded that dietary nitrate (NO3−) improves maximal neuromuscular power in humans, but these were based on a limited number of studies. This is the first systematic review and meta-analysis evaluating the effects of dietary NO3− supplementation on muscular power in humans. The study also aims to quantify the size of this beneficial effect. 19 studies with a total of 268 participants were included. Most of these used concentrated beetroot juice as the source of NO3− given as an acute dose (short term high level). A positive effect of dietary NO3− on muscle power was observed in all 19 studies. Analyses were done on sub groups - age, sex and the amount of muscle mass engaged in the activity. Dietary NO3− intake significantly increases maximal muscle power in humans. The magnitude of this effect has practical and clinical importance; not just for athletes but also for patient groups. This effect is independent of subject age, sex, or the amount of muscle mass engaged in the activity but may be greater with acute vs. repeated dosing. Further research is needed to determine factors such as the optimal supplementation regimen and target population.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This meta-analysis lends quantitative support to previous narrative reviews that nitrate supplementation can enhance maximal power output.
- These findings are highly relevant to team and strength sport athletes, who may not otherwise be supplementing with nitrates.
- These findings are also highly relevant for older populations, where risk of falls and fractures are high and can lead to significant adverse effects on health and quality of life.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
- In 2007, researchers uncovered the ingestion of dietary nitrates reduced the oxygen cost of submaximal exercise, and since, over 100 studies have examined the effects of nitrates on endurance performance.
- With regards to the impact of nitrates on maximal force output, only trivial results had been previously found.
- This review study found that while nitrates do not impact force development, they do demonstrate primary effect on the speed of muscle contraction (i.e. muscular power is the product of force x speed).
- The reviews primary finding was that nitrate intake can significantly enhance muscular power, regardless of subject age or sex.
Clinical practice applications:
- These new findings highlight the ability of dietary nitrates to improve neuromuscular power production is highly relevant for team sport athletes, due to the explosive nature of these sports with constant accelerations and decelerations during training and competition.
- In the general population, falls and fractures amongst older adults significantly reduces quality of life and costs the healthcare system hundreds of millions of pounds to treat.
- Improved contractile properties of muscle, most notably speed of contraction, may offer protection to older adults as well as the benefit of additional nitric oxide (NO) to support vascular health as well.
- The typical intake of dietary nitrates in the general population is about 31-185mg/day in Europe and 40-100mg/day in North America. Most studies use doses between 300-600mg of dietary nitrates. Increasing dietary or supplemental intake is key to achieving the neuromuscular effect.
Considerations for future research:
- The results of the present meta-analysis clearly demonstrate that dietary nitrates increases muscle power in humans, but the mechanism responsible for this effect is still unclear.
- There are notable differences between rodent and human metabolism of dietary nitrates, therefore the biochemical mechanism by which nitrate intake improves human muscle power requires additional study.
Abstract
BACKGROUND Previous narrative reviews have concluded that dietary nitrate (NO3-) improves maximal neuromuscular power in humans. This conclusion, however, was based on a limited number of studies, and no attempt has been made to quantify the exact magnitude of this beneficial effect. Such information would help ensure adequate statistical power in future studies and could help place the effects of dietary NO3- on various aspects of exercise performance (i.e., endurance vs. strength vs. power) in better context. We therefore undertook a systematic review and individual participant data meta-analysis to quantify the effects of NO3- supplementation on human muscle power. METHODS The literature was searched using a strategy developed by a health sciences librarian. Data sources included Medline Ovid, Embase, SPORTDiscus, Scopus, Clinicaltrials.gov , and Google Scholar. Studies were included if they used a randomized, double-blind, placebo-controlled, crossover experimental design to measure the effects of dietary NO3- on maximal power during exercise in the non-fatigued state and the within-subject correlation could be determined from data in the published manuscript or obtained from the authors. RESULTS Nineteen studies of a total of 268 participants (218 men, 50 women) met the criteria for inclusion. The overall effect size (ES; Hedge's g) calculated using a fixed effects model was 0.42 (95% confidence interval (CI) 0.29, 0.56; p = 6.310 × 10- 11). There was limited heterogeneity between studies (i.e., I2 = 22.79%, H2 = 1.30, p = 0.3460). The ES estimated using a random effects model was therefore similar (i.e., 0.45, 95% CI 0.30, 0.61; p = 1.064 × 10- 9). Sub-group analyses revealed no significant differences due to subject age, sex, or test modality (i.e., small vs. large muscle mass exercise). However, the ES in studies using an acute dose (i.e., 0.54, 95% CI 0.37, 0.71; p = 6.774 × 10- 12) was greater (p = 0.0211) than in studies using a multiple dose regimen (i.e., 0.22, 95% CI 0.01, 0.43; p = 0.003630). CONCLUSIONS Acute or chronic dietary NO3- intake significantly increases maximal muscle power in humans. The magnitude of this effect-on average, ~ 5%-is likely to be of considerable practical and clinical importance.
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Effects of Nutrition/Diet on Brown Adipose Tissue in Humans: A Systematic Review and Meta-Analysis.
Heenan, KA, Carrillo, AE, Fulton, JL, Ryan, EJ, Edsall, JR, Rigopoulos, D, Markofski, MM, Flouris, AD, Dinas, PC
Nutrients. 2020;12(9)
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The body has many uses for the energy that is consumed in the diet, one of these is for the generation of heat. Brown adipose tissue (BAT), which is stored in the lower neck, collarbone, abdomen and along the spine, is a special type of fat that is activated when the body is cold and serves to generate heat. The activity of this fat is of benefit to humans, as it reduces weight gain, improves blood sugar balance, and helps reduce blood lipid levels, reducing the risk for heart disease and type 2 diabetes. This systematic review of 24 publications aimed to determine whether nutrition and/or diet affects the activity of BAT. The results showed that there was no change in BAT activity following a high calorie carbohydrate rich meal, a standard meal and during overfeeding. Supplementation of L-Arginine, which is a supplement that helps the body build muscle, also had no effect on BAT activity. It was concluded that BAT activity was not affected by nutrition or diet. This study could be used by healthcare professionals to understand that the effect of diet on risk for heart disease and type 2 diabetes may not involve the modification of BAT.
Abstract
BACKGROUND Brown adipose tissue (BAT) provides a minor contribution to diet-induced thermogenesis (DIT)-the metabolic response to food consumption. Increased BAT activity is generally considered beneficial for mammalian metabolism and has been associated with favorable health outcomes. The aim of the current systematic review was to explore whether nutritional factors and/or diet affect human BAT activity. METHODS We searched PubMed Central, Embase and Cochrane Library (trials) to conduct this systematic review (PROSPERO protocol: CRD42018082323). RESULTS We included 24 eligible papers that studied a total of 2785 participants. We found no mean differences in standardized uptake value of BAT following a single meal or after 6 weeks of L-Arginine supplementation. Resting energy expenditure (REE), however, was increased following a single meal and after supplementation of capsinoid and catechin when compared to a control condition (Z = 2.41, p = 0.02; mean difference = 102.47 (95% CI = 19.28-185.67)). CONCLUSIONS Human BAT activity was not significantly affected by nutrition/diet. Moreover, REE was only increased in response to a single meal, but it is unlikely that this was due to increased BAT activity. BAT activity assessments in response to the chronic effect of food should be considered along with other factors such as body composition and/or environmental temperature.