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Effects of dietary glycemic index on brain regions related to reward and craving in men
Open accessAbstract
Background Qualitative aspects of diet influence eating behavior, but the physiologic mechanisms for these calorie-independent effects remain speculative.Objective We examined effects of the glycemic index (GI) on brain activity in the late postprandial period after a typical intermeal interval.Design With the use of a randomized, blinded, crossover design, 12 overweight or obese men aged 18-35 y consumed high- and low-GI meals controlled for calories, macronutrients, and palatability on 2 occasions. The primary outcome was cerebral blood flow as a measure of resting brain activity, which was assessed by using arterial spin-labeling functional magnetic resonance imaging 4 h after test meals. We hypothesized that brain activity would be greater after the high-GI meal in prespecified regions involved in eating behavior, reward, and craving.Results Incremental venous plasma glucose (2-h area under the curve) was 2.4-fold greater after the high- than the low-GI meal (P = 0.0001). Plasma glucose was lower (mean ± SE: 4.7 ± 0.14 compared with 5.3 ± 0.16 mmol/L; P = 0.005) and reported hunger was greater (P = 0.04) 4 h after the high- than the low-GI meal. At this time, the high-GI meal elicited greater brain activity centered in the right nucleus accumbens (a prespecified area; P = 0.0006 with adjustment for multiple comparisons) that spread to other areas of the right striatum and to the olfactory area.Conclusions Compared with an isocaloric low-GI meal, a high-GI meal decreased plasma glucose, increased hunger, and selectively stimulated brain regions associated with reward and craving in the late postprandial period, which is a time with special significance to eating behavior at the next meal. This trial was registered at clinicaltrials.gov as NCT01064778.
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TL;DR
In a randomized, blinded crossover trial in overweight or obese men, a high-glycemic-index meal compared with an isocaloric low-glycemic-index meal produced lower late postprandial plasma glucose, greater hunger, and greater resting activity in the right nucleus accumbens/striatum 4 h later. These findings suggest high-GI meals may stimulate brain reward and craving circuitry during the late postprandial period.
Key findings
- The 2-h incremental plasma glucose AUC was 2.4-fold greater after the high-GI than low-GI meal (2.9 ± 0.36 vs. 1.2 ± 0.27 mmol·h/L; P = 0.0001), and the 2-h insulin AUC was also greater (127.1 ± 18.1 vs. 72.8 ± 9.78 mU·h/mL; P = 0.003).
- At 4 h, plasma glucose was lower after the high-GI meal (4.7 ± 0.14 vs. 5.3 ± 0.16 mmol/L; P = 0.005), and hunger was greater (P = 0.04); the 5-h hunger AUC was also greater after the high-GI meal (P = 0.04).
- Cerebral blood flow was greater 4 h after the high-GI meal in the right nucleus accumbens (mean difference: 4.4 ± 0.56 mL·100 g⁻¹·min⁻¹; range: 2.1–7.3; 8.2% relative difference), remaining significant after Bonferroni correction for 25 prespecified regions (P = 0.0006) and after correction for all 334 nonredundant brain regions (P = 0.009); activity spread to other right striatal areas and the olfactory area.
- No differences were observed in the contralateral striatum or other prespecified regions of interest; meal palatability did not differ (5.5 ± 0.67 vs. 5.3 ± 0.65 cm; P = 0.7).
Methods
- Randomized, blinded, crossover study in 12 overweight or obese men aged 18–35 y (BMI ≥25) who consumed high- and low-GI liquid test meals on 2 occasions separated by 2–8 wk; meals were controlled for calories (25% of estimated daily energy requirements), macronutrients, ingredient sources, and palatability, with predicted GI values of 84% and 37%.
- The primary outcome was resting cerebral blood flow measured by arterial spin-labeling fMRI 4 h after test meals; secondary outcomes included plasma glucose, serum insulin, and hunger over the 5-h postprandial period.
- Analyses used prespecified brain regions of interest, paired 2-tailed t tests adjusted for order effect with Bonferroni correction for 25 regions, and voxel-wise general linear model analysis at P ≤ 0.002; imaging data were usable for 11 participants because of a data-storage error.
Limitations
- The paper states the main limitations: small sample size and exclusive focus on overweight and obese men, with no lean controls, women, or pre- and post-weight-loss participants; hedonic responses and food cravings were not directly assessed; and liquid test meals limit generalizability to solid meals.
- The paper states that venous rather than arterialized blood sampling could have caused error in measuring arterial blood glucose concentrations above and below fasting, especially for the high-GI meal.
- The paper notes an unanticipated right-hemisphere-only effect and that lack of differences in other prespecified regions could reflect insufficient power or true absence of effects at 4 h; it also states that the small size increases risk of a false-negative but not false-positive finding.
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27 Not checked yet · 20 Own method · 17 Own result · 2 Own interpretation · 2 No basis given
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
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“Incremental venous plasma glucose (2-h area under the curve) was 2.4-fold greater after the high-than the low-GI meal (P = 0.0001).”
- Also stated in: § Subjective and biochemical responses to test meals · plain
“Consistent with the predicted GI (Table 1), the incremental 2-h AUC for glucose was 2.4-fold greater after the high-than low-GI test meal (2.9 6 0.36 compared with 1.2 6 0.27 mmol $ h/L, respectively; P = 0.0001) (Figure 2).”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > Abstract
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- Also stated in: § Subjective and biochemical responses to test meals · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At this time, the high-GI meal elicited greater brain activity centered in the right nucleus accumbens (a prespecified area; P = 0.0006 with adjustment for multiple comparisons) that spread to other areas of the right striatum and to the olfactory area.”
- Also stated in: § Brain imaging · plain
“An image-based analysis showed a single region in the right nucleus accumbens at Montreal Neurologic Institute/International Consortium for Brain Mapping coordinates 8, 8, 210 (peak t = 9.34) and another local maximum at coordinates 12, 12, 2 (t = 5.16), which spread to other areas of the right striatum (caudate, putamen, and globus pallidus) and olfactory area (Figure 3).”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > Abstract
plaindirectn = 12- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Brain imaging · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At this time, the high-GI meal elicited greater brain activity centered in the right nucleus accumbens (a prespecified area; P = 0.0006 with adjustment for multiple comparisons) that spread to other areas of the right striatum and to the olfactory area.”
- Also stated in: § Brain imaging · plain
“Cerebral blood flow was greater 4 h after the high-than low-GI meal in the right nucleus accumbens (mean difference: 4.4 6 0.56 mL $ 100 g 21 $ min 21 ; range: 2.1-7.3 mL $ 100 g 21 $ min 21 ; an 8.2% relative difference).”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > Abstract
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- Also stated in: § Brain imaging · plain
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“We did not observe differences in the contralateral striatum or other prespecified regions of interest.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > Brain imaging
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Plasma glucose was lower (mean 6 SE: 4.7 6 0.14 compared with 5.3 6 0.16 mmol/L; P = 0.005) and reported hunger was greater (P = 0.04) 4 h after the high-than the low-GI meal.”
- Also stated in: § Subjective and biochemical responses to test meals · plain
“At 4 h into the postprandial period, the blood glucose concentration was lower (4.7 6 0.14 compared with 5.3 6 0.16 mmol/L, P = 0.005), and the change in hunger from baseline was greater (1.65 6 0.79 compared with 20.01 cm 6 0.92; P = 0.04) after the high-than low-GI test meal, respectively.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > Abstract
plaindirectn = 12- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Subjective and biochemical responses to test meals · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The incremental 2-h AUC for insulin (127.1 6 18.1 compared with 72.8 6 9.78 mU $ h/mL; P = 0.003) and incremental 5-h AUC for hunger (0.45 6 2.75 compared with 25.2 6 3.73 cm $ h; P = 0.04) were also greater after the high-than low-GI test meal, respectively.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > Subjective and biochemical responses to test meals
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Plasma glucose was lower (mean 6 SE: 4.7 6 0.14 compared with 5.3 6 0.16 mmol/L; P = 0.005) and reported hunger was greater (P = 0.04) 4 h after the high-than the low-GI meal.”
- Also stated in: § Subjective and biochemical responses to test meals · plain
“At 4 h into the postprandial period, the blood glucose concentration was lower (4.7 6 0.14 compared with 5.3 6 0.16 mmol/L, P = 0.005), and the change in hunger from baseline was greater (1.65 6 0.79 compared with 20.01 cm 6 0.92; P = 0.04) after the high-than low-GI test meal, respectively.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > Abstract
plaindirectn = 12- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Subjective and biochemical responses to test meals · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The incremental 2-h AUC for insulin (127.1 6 18.1 compared with 72.8 6 9.78 mU $ h/mL; P = 0.003) and incremental 5-h AUC for hunger (0.45 6 2.75 compared with 25.2 6 3.73 cm $ h; P = 0.04) were also greater after the high-than low-GI test meal, respectively.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > Subjective and biochemical responses to test meals
plaindirect- Asserted: passes — The authors put it forward as true.
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“The predicted GI of the high-and low-GI test meals were 84% and 37%, respectively, by using glucose as the reference standard.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > Test meals
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“We also did not observe differences in other prespecified brain regions, either because our study lacked power to see less robust effects or because such effects did not occur at the 4-h time point.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
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“The palatability of high-and low-GI test meals did not differ according to responses on the 10-cm VAS (5.5 6 0.67 compared with 5.3 6 0.65 cm, respectively; P = 0.7).”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > Subjective and biochemical responses to test meals
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“we showed that the consumption of a highcompared with a low-GI test meal increased the activity in brain regions related to food intake, reward, and craving in the late postprandial period”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
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“For all areas depicted, the blood flow was greater after the high-than after the low-GI meal.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
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“Previous studies have typically limited the duration of observation to #1 h after food consumption, when glucose absorption peaks and a high-GI meal may transiently appear to provide benefits to brain function (33).”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [33] Page, 2013, Effects of fructose vs glucose on regional cerebral blood flow in brain regions involved with appetite and reward pathways, JAMA source
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“Clinical studies that used functional brain imaging have reported greater activation in the nucleus accumbens or other regions of the striatum in obese than lean individuals after they viewed or consumed palatable, high-calorie food (6)(7)(8)(9)(10)(11).”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > INTRODUCTION
What the sources say
- Not checked yetcites (6)(7)(8)(9)(10)(11)
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In the paper
“Compared with an isocaloric low-GI meal, a high-GI meal decreased plasma glucose, increased hunger, and selectively stimulated brain regions associated with reward and craving in the late postprandial period, which is a time with special significance to eating behavior at the next meal.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > Abstract
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“The attained sample of 11 participants with useable data provided 80% power to detect a difference of 12.4%, with all other assumptions remaining.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > Statistical analyses
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“Third, we focused on a spe-cific dietary factor by controlling for calorie content, macronutrient composition, ingredient sources, and food form, instead of comparing grossly different foods (eg, cheesecake compared with vegetables) (6,10,31,32).”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [6] Bruce, 2010, Obese children show hyperactivation to food pictures in brain networks linked to motivation, reward and cognitive control, Int J Obes (Lond) source
- Not checked yetcites [10] Stoeckel, 2008, Widespread reward-system activation in obese women in response to pictures of high-calorie foods, Neuroimage source
- Not checked yetcites [31] Dimitropoulos, 2012, Greater corticolimbic activation to high-calorie food cues after eating in obese vs. normal-weight adults, Appetite source
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“In addition, the liquid form of the test meals limited the generalizability of findings to solid meals.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
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“With ASL, we were able to examine persistent effects of test meals without superimposed stimuli (eg, pictures of high-calorie foods).”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
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In the paper
“The decline in blood glucose (and other metabolic fuels) (13,14) in the late postprandial period after a high-GI meal would not only constitute a powerful homeostatic hunger signal (15)”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [13] Ludwig, 2002, The glycemic index: physiological mechanisms relating to obesity, diabetes, and cardiovascular disease, JAMA source
- Not checked yetcites [14] Ludwig, 1999, High glycemic index foods, overeating, and obesity, Pediatrics source
- Not checked yetcites [15] Campfield, 1996, Human eating: evidence for a physiological basis using a modified paradigm, Neurosci Biobehav Rev source
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“the glycemic load (the multiplicative product of GI and carbohydrate amount) (30) of the US diet has risen substantially in the past half century”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [30] Salmerón, 1997, Dietary fiber, glycemic load, and risk of NIDDM in men, Diabetes Care source
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“Indeed, in a study of lean and obese adults, a mean insulininduced decrease in blood glucose concentrations from 4.9 to 3.7 mmol/L increased the food-stimulus activation of the striatum and desire for high-calorie foods (18).”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > INTRODUCTION
What the sources say
- Not checked yetcites [18] Page, 2011, Circulating glucose levels modulate neural control of desire for high-calorie foods in humans, J Clin Invest source
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“Thus, the findings have relevance to high-GI breakfasts commonly consumed in the United States (eg, a bagel and fat-free cream cheese) (12).”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [12] Atkinson, 2008, International tables of glycemic index and glycemic load values: 2008, Diabetes Care source
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“this secular trend may adversely affect both systems that regulate food intake.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: The US food supply has changed radically, with rapidly increasing consumption of highly processed food products derived primarily from grain commodities.
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“However, these cross-sectional comparisons between groups of lean and obese people could not assess the causal direction.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > INTRODUCTION
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“Of particular interest, striatal dopamine D 2 receptor availability was significantly lower in obese individuals than in nonobese matched controls (11), which raised the possibility that overeating may compensate for low dopaminergic activity.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > INTRODUCTION
What the sources say
- Not checked yetcites [11] Wang, 2001, Brain dopamine and obesity, Lancet source
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“In rodent studies, extracellular concentrations of dopamine and its metabolites in the nucleus accumbens increased more after the consumption of highly palatable food than standard rodent feed pellets (4).”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > INTRODUCTION
What the sources say
- Not checked yetcites [4] Martel, 1996, Mesolimbic dopaminergic system activity as a function of food reward: a microdialysis study, Pharmacol Biochem Behav source
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“but also increase the hedonic value of food through striatal activation (18).”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [18] Page, 2011, Circulating glucose levels modulate neural control of desire for high-calorie foods in humans, J Clin Invest source
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- It may state two separate claims as one. 23
- Probably not a substantial claim. 24
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“This difference remained significant after Bonferroni correction for the 25 prespecified anatomic regions of interest (P = 0.0006) and after correction for all 334 nonredundant brain regions (P = 0.009).”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > Brain imaging
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“All variables related to plasma glucose, serum insulin, and hunger were significantly related to blood flow in the right nucleus accumbens, whereas the palatability of meals was not.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > Brain imaging
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“Differences between high-and low-GI meals were significant at 4 h (the time point of interest) for all 3 outcomes by using paired t tests.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
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“which was coincident with lower blood glucose and greater hunger.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
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It may state two separate claims as one.
In the paper
“The use of venous blood could have caused an error in the measurement of arterial blood glucose concentrations above and below fasting concentrations, especially for the high-GI meal, which comprised a study limitation (22).”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > Procedures
What the sources say
- Not checked yetcites [22] Brouns, 2005, Glycaemic index methodology, Nutr Res Rev source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Adjustment for the order effect did not materially affect these outcomes.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > Statistical analyses
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The decrease in blood glucose, which often falls below fasting concentrations by 4 h after a high-GI meal, may lead to excessive hunger, overeating, and a preference for foods that rapidly restore blood glucose to normal (ie, high GI) (15)(16)(17), propagating cycles of overeating.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > INTRODUCTION
What the sources say
- Not checked yetcites (15)(16)(17)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Beyond reward and craving, the nucleus accumbens is crucially involved in substance abuse and dependence (36-38)”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [36] Di Chiara, 1999, Drug addiction as a disorder of associative learning. Role of nucleus accumbens shell/extended amygdala dopamine, Ann N Y Acad Sci source
- Not checked yetcites [37] Feltenstein, 2008, The neurocircuitry of addiction: an overview, Br J Pharmacol source
- Not checked yetcites [38] Kalivas, 2005, The neural basis of addiction: a pathology of motivation and choice, Am J Psychiatry source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Women were not included in this initial study to avoid the confounding that might have arisen from the menstrual cycle (19).”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > Participants
What the sources say
- Not checked yetcites [19] Frank, 2010, Effect of menstrual cycle phase on corticolimbic brain activation by visual food cues, Brain Res source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Statistical treatments included the prespecification of brain regions of interest and correction for multiple comparisons.”
- Also stated in: § Statistical analyses · plain
“Of a total 334 nonredundant anatomic regions throughout the brain, prespecified areas of interest encompassed 25 separate regions (see Supplemental Table 1 under “Supplemental data” in the online issue).”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > SUBJECTS AND METHODS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
- Also stated in: § Statistical analyses · plain
None of the sources cited for this claim have been checked yet.
In the paper
“The GI describes how carbohydrate-containing foods affect blood glucose in the postprandial state (12,13).”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > INTRODUCTION
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“the chemical manipulation of the nucleus accumbens in rats resulted in the stimulation of orexigenic neurons and inhibition of anorexigenic neurons in the hypothalamus (35)”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [35] Zheng, 2003, Peptides that regulate food intake: appetite-inducing accumbens manipulation activates hypothalamic orexin neurons and inhibits POMC neurons, Am J Physiol Regul Integr Comp Physiol source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“The mesolimbic dopaminergic system of the brain, which converges on the nucleus accumbens (part of the striatum), plays a central role in reward and craving, and this system appears to mediate hedonic food responses (1)(2)(3).”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > INTRODUCTION
What the sources say
- Not checked yetcites (1)(2)(3)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Our study, despite its size, had robust power to test the a priori hypothesis with adjustment for multiple comparisons.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Main study limitations included the small size and an exclusive focus on overweight and obese men.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Small studies limit generalizability and increase risk of a false-negative (but not false-positive) finding.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Imaging data for one participant were incomplete because of a data-storage error; the other participants completed the protocol uneventfully.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > Study participants
plainn = 12- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“we used ASL, which is a novel imaging technique that provides a quantitative measure of cerebral blood flow.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The conventional method (blood oxygenation level-dependent fMRI) assesses acute changes in brain activity, not absolute differences, which typically limits observations to a few minutes after a physiologic perturbation.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This combination of physiologic events may foster food cravings with a special preference for high-GI carbohydrates (16, 17), thereby propagating cycles of overeating.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Second, we used a crossover intervention rather than a cross-sectional comparison between groups (eg, lean compared with obese), which provided increased statistical power and evidence for causal direction.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Fourth, the 2 test meals were designed and documented to have a similar palatability, which helped to disentangle metabolic effects from immediate hedonic responses.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All participants and research staff involved in data collection were masked to the intervention sequence.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > Participants
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“and in subjects who scored high on a measure of food addiction (39).”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [39] Gearhardt, 2011, Neural correlates of food addiction, Arch Gen Psychiatry source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Nevertheless, the validity of the concept of food addiction remains vigorously debated (41)(42)(43)(44)(45)(46)(47).”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [41] Benton, 2010, The plausibility of sugar addiction and its role in obesity and eating disorders, Clin Nutr source
- Not checked yetcites [42] Blumenthal, 2010, Neurobiology of food addiction, Curr Opin Clin Nutr Metab Care source
- Not checked yetcites [43] Corwin, 2009, Symposium overview–food addiction: fact or fiction?, J Nutr source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This trial was registered at clinicaltrials.govas NCT01064778.”
- Also stated in: § SUBJECTS AND METHODS · plain
“The trial was registered at clinicaltrials.gov as NCT01064778, and participants provided written informed consent.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Also stated in: § SUBJECTS AND METHODS · plain
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We did not assess hedonic responses to the meals or food cravings directly, and therefore, we could not explore the relation between these subjective values and brain activation.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Neuroimaging was performed at 4 h after the test meal, when the blood glucose nadir after the high-GI meal was expected (14), by using a GE 3Tesla whole-body scanner (GE Healthcare).”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > Measurements
What the sources say
- Not checked yetcites [14] Ludwig, 1999, High glycemic index foods, overeating, and obesity, Pediatrics source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“In addition, the recurrent activation of the striatum may downregulate dopamine receptor availability and further heighten the drive to overeat (11).”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [11] Wang, 2001, Brain dopamine and obesity, Lancet source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Sixth, we used mixed meals with a macronutrient composition and dietary glycemic load within prevailing ranges.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“a study that compared insulin-sensitive compared with insulinresistant men showed a differential effect of systemic insulin administration on glucose metabolism for the right, but not left, ventral striatum (34).”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [34] Anthony, 2006, Attenuation of insulin-evoked responses in brain networks controlling appetite and reward in insulin resistance: the cerebral basis for impaired control of food intake in metabolic syndrome?, Diabetes source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Furthermore, microinjections of opiate into the nucleus accumbens increased food intake and the reward value of food (5).”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > INTRODUCTION
What the sources say
- Not checked yetcites [5] Peciña, 2000, Opioid site in nucleus accumbens shell mediates eating and hedonic ’liking’ for food: map based on microinjection Fos plumes, Brain Res source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The study was designed to provide 80% power by using a 5% type I error rate to detect a difference in cerebral blood flow of 11.8%, assuming a sample size of 12 participants, residual SD of 11% for a single measurement, and intrasubject correlation of 0.6.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > Statistical analyses
plainn = 12- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“As shown in Table 1, both test meals were composed of similar ingredients and had the same macronutrient distribution (ProNutra Software, version 3.3.0.10;Viocare Technologies Inc).”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > Test meals
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Recent studies that used the conventional blood oxygenation level-dependent fMRI have shown selective overactivity in the nucleus accumbens and related brain areas in obese compared with lean individuals when shown imagines of highly palatable food (6)(7)(8)(9)(10)(11)”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [6] Bruce, 2010, Obese children show hyperactivation to food pictures in brain networks linked to motivation, reward and cognitive control, Int J Obes (Lond) source
- Not checked yetcites [7] Holsen, 2012, Importance of reward and prefrontal circuitry in hunger and satiety: Prader-Willi syndrome vs simple obesity, Int J Obes (Lond) source
- Not checked yetcites [8] Rothemund, 2007, Differential activation of the dorsal striatum by high-calorie visual food stimuli in obese individuals, Neuroimage source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Enrolled participants were entered sequentially onto a list of random assignments (prepared by the Clinical Research Center at Boston Children's Hospital) for the order of test meals by using randomly permuted blocks of 4.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > Participants
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Both test meals had a similar appearance, smell, and taste.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > Participants
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“Food intake is regulated by hedonic and homeostatic systems (3) that historically served to maintain mean BMI within a healthy range under widely varying environmental conditions.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
What the sources say
- Not checked yetcites [3] Lutter, 2009, Homeostatic and hedonic signals interact in the regulation of food intake, J Nutr source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast to previous research, our study used test meals of similar palatability and ASL methods to examine unstimulated brain activity after 4 h.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“These neurophysiologic findings, together with longer feeding studies of weight-loss maintenance (48,49), suggest that a reduced consumption of high-GI carbohydrates (specifically, highly processed grain products, potatoes, and concentrated sugar) may ameliorate overeating and facilitate maintenance of a healthy weight in overweight and obese individuals.”
§ Effects of dietary glycemic index on brain regions related to reward and craving in men 1-4 > DISCUSSION
What the sources say
hedgedconditionaln = 11- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
The late postprandial period is a time with special significance to eating behavior at the next meal.
“Compared with an isocaloric low-GI meal, a high-GI meal decreased plasma glucose, increased hunger, and selectively stimulated brain regions associated with reward and craving in the late postprandial period, which is a time with special significance to eating behavior at the next meal.”
The paper relies on this without support.
The US food supply has changed radically, with rapidly increasing consumption of highly processed food products derived primarily from grain commodities.
“the food supply has changed radically, with the rapidly increasing consumption of highly processed food products derived primarily from grain commodities.”
The paper relies on this without support.
Small studies limit generalizability and increase risk of a false-negative (but not false-positive) finding.
“Small studies limit generalizability and increase risk of a false-negative (but not falsepositive) finding.”
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?
In the citing paper
“Such rapidly digested, low-fiber carbohydrates drive many obesogenic pathways. 45, 46, 48-50”
From Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review (2016) · cites this paper as [49]
In the citing paper
“This rapid digestion may induce multiple adverse effects, potentially stimulating reward/craving areas in the brain, activating hepatic de novo lipogenesis, increasing uric acid production, and promoting visceral adiposity.49, 162-166”
From Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review (2016) · cites this paper as [49]
Citations
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Molecular Mechanisms of Depression: Perspectives on New Treatment Strategies
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Genetics of Food Intake Self-Regulation in Childhood: Literature Review and Research Opportunities
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International table of glycemic index and glycemic load values: 2002,
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The Neural Basis of Addiction: A Pathology of Motivation and Choice
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“The calorie content of test meals was individually determined to provide each participant with 25% of daily energy requirements on the basis of an estimate of resting energy expenditure (21) and an activity factor of 1.”
BackgroundInternational Tables of Glycemic Index and Glycemic Load Values: 2008
Atkinson, F. S., Foster-Powell, K., & Brand-Miller, J. C. (2008) · Diabetes Care · doi:10.2337/dc08-1239 · Cited by 1,965
Wang, G.-J., Volkow, N. D., Logan, J., Pappas, N. R., Wong, C. T., Zhu, W., Netusll, N., & Fowler, J. S. (2001) · The Lancet · doi:10.1016/s0140-6736(00)03643-6 · Cited by 1,864
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Self-citationBias between MNI and Talairach coordinates analyzed using the ICBM‐152 brain template
Lancaster, J. L., Tordesillas‐Gutiérrez, D., Martinez, M., Salinas, F., Evans, A., Zilles, K., Mazziotta, J. C., & Fox, P. T. (2007) · Human Brain Mapping · doi:10.1002/hbm.20345 · Cited by 1,464
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Benjamin, E. J., Blaha, M. J., Chiuve, S. E., Cushman, M., Das, S. R., Deo, R., de Ferranti, S. D., Floyd, J., Fornage, M., Gillespie, C., et al. (2017) · Circulation · doi:10.1161/cir.0000000000000485 · Cited by 12,591
Heart Disease and Stroke Statistics—2016 Update: A Report From the American Heart Association
Mozaffarian, D., Benjamin, E. J., Go, A. S., Arnett, D. K., Blaha, M. J., Cushman, M., Das, S. R., de Ferranti, S., Després, J.-P., Fullerton, H. J., et al. (2016) · Circulation · doi:10.1161/cir.0000000000000350 · Cited by 6,596
Heart Disease and Stroke Statistics—2015 Update: A Report From the American Heart Association
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Heart Disease and Stroke Statistics—2014 Update
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Metadata
- Authors
- Lennerz, B. S., Alsop, D. C., Holsen, L. M., Stern, E., Rojas, R., Ebbeling, C. B., Goldstein, J. M., & Ludwig, D. S.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Ludwig, David S
- ORCID
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 98
- Issue
- 3
- Pages
- 641-647
- ISSN
- 0002-9165 (ISSN-L)
- PMC
- PMC3743729
- OpenAlex
- W2164163218
- Semantic Scholar
- a012f8c995e712b5a007ecf44a8941ef88859b6b
- Cited by
- 140
- References
- 53
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 6 · 2023: 7 · 2022: 8 · 2021: 8 · 2020: 9 · 2019: 9 · 2018: 14 · 2017: 12 · 2016: 12 · 2015: 18 · 2014: 13 · 2013: 6
- FWCI
- 8.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Harvard University
- Harvard Catalyst (UL1-RR025758, UL1 RR025758-01, RR025758)
- Pediatric Endocrine Society
- Endocrine Fellows Foundation
- National Institutes of Health (UL1RR02575801, RR025758, RR025758-01)
- National Institute of Mental Health (R01MH080729)
- National Institute of Diabetes and Digestive and Kidney Diseases (K24DK082730)
- National Center for Research Resources (UL1RR025758, RR025758, RR 025758-01)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Nursing › Nutrition and Dietetics › Food composition and properties
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Keywords
- glycemic index, cerebral blood flow, nucleus accumbens, striatum, olfactory cortex, reward, craving, hunger, postprandial blood glucose, dietary habits, obesity, overweight men, arterial spin labeling
- MeSH terms
- Adult, Appetite, Blood Glucose, Brain, Brain Mapping, Female, Humans, Hunger, Male, Obesity, Regional Blood Flow, Reward, Postprandial Period, Area Under Curve, Glycemic Index, Young Adult
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.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
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 ›
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