Article

Low Carbohydrate, High Fat Diet Increases C-Reactive Protein during Weight Loss

April 2007
Journal of the American College of Nutrition 26(2):163-9

DOI:10.1080/07315724.2007.10719598

Source
PubMed

Authors:

University of Cincinnati

Chronic inflammation is associated with elevated risk of heart disease and may be linked to oxidative stress in obesity. Our objective was to evaluate the effect of weight loss diet composition (low carbohydrate, high fat, LC or high carbohydrate, low fat, HC) on inflammation and to determine whether this was related to oxidative stress. Twenty nine overweight women, BMI 32.1 +/- 5.4 kg/m(2), were randomly assigned to a self-selected LC or HC diet for 4 wks. Weekly group sessions and diet record collections helped enhance compliance. Body weight, markers of inflammation (serum interleukin-6, IL-6; C-reactive protein, CRP) oxidative stress (urinary 8-epi-prostaglandin F2alpha, 8-epi) and fasting blood glucose and free fatty acids were measured weekly. The diets were similar in caloric intake (1357 kcal/d LC vs. 1361 HC, p=0.94), but differed in macronutrients (58, 12, 30 and 24, 59, 18 for percent of energy as fat, carbohydrate, and protein for LC and HC, respectively). Although LC lost more weight (3.8 +/- 1.2 kg LC vs. 2.6 +/- 1.7 HC, p=0.04), CRP increased 25%; this factor was reduced 43% in HC (p=0.02). For both groups, glucose decreased with weight loss (85.4 vs. 82.1 mg/dl for baseline and wk 4, p<0.01), while IL-6 increased (1.39 to 1.62 pg/mL, p=0.04). Urinary 8-epi varied differently over time between groups (p<0.05) with no consistent pattern. Diet composition of the weight loss diet influenced a key marker of inflammation in that LC increased while HC reduced serum CRP but evidence did not support that this was related to oxidative stress.

The impact of high-intensity interval training on cardiometabolic factors in adults with overweight and obesity: a systematic review and meta-analysis

Article

May 2024

Background and purpose: Excessive fat deposition is associated with cardiovascular diseases, diabetes as well as hypertension. The aim of this study was to determine the net effect size of high intensity interval training (HIIT) on some factors associated with insulin sensitivity in adults with overweight and obesity. Materials and methods: A search for English articles was conducted in Web of Science, Scopus, and PubMed databases without limiting the year of publication until February 2023. To calculate the effect size, WMD and 95% confidence interval were calculated using random effect model. Fixed effect model meta regression was used to determine treatment effects associations with other variables. Results: In total, 13 studies with 446 adults with overweight and obesity (149 females, and 317 males) with 24.7-57 years old were included in the present meta-analysis. The results showed that HIIT caused a significant decrease in fasting glucose [WMD=-8.65 mg/dL, P=0.002], fasting insulin [WMD=-1.88 U/L P=0.005], and diastolic blood pressure (DBP) [WMD=-3.33 mmHg. Weak correlations were observed in between HIIT’s net effect on DBP and insulin (r=-0.32, p=0.019) as well as with subjects’ age (r=-0.29, p=0.037) respectively in meta-regression assessments. Conclusion: The rate of DBP reduction is sharper and these changes are also correlated with age. Therefore, HIIT is suggested as a Non-pharmacological Approach to prevent against future cardiometabolic risk factors in this population.

Effects of low-carbohydrate diets, with and without caloric restriction, on inflammatory markers in adults: a systematic review and meta-analysis of randomized clinical trials

Article

Mar 2024
EUR J CLIN NUTR

Low-carbohydrate diets (LCDs) have gained interest due to their favorable effects on health outcomes, such as inflammation. However, further research is needed to ascertain the overall effects of LCDs on inflammatory parameters, but at the same time considering weight loss and calorie intake. Thus, a systematic review and meta-analysis of randomized clinical trials was performed to investigate the effects of LCDs compared with low-fat diets (LFDs), with and without caloric restriction, on inflammatory markers in adults. PubMed, Scopus, and Web of Science were searched through March 2022 to select intervention studies addressing LCDs vs. LFDs, in which the following circulating inflammatory markers were used: C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and interleukin (IL-6). Analyses were conducted comparing LCDs vs. LFDs through weighted mean differences (WMD) or standardized mean differences (SMD) and 95% confidence intervals (95% CIs) using random effects models. The systematic review and meta-analysis included a total of 51 studies with a total sample of 4,164 adults, with or without other chronic diseases. Intervention durations ranged from 2–144 weeks. LCDs, compared with LFDs, significantly decreased body weight [WMD = −1.35%, p = 0.001], CRP [SMD = −0.1, p = 0.03], and IL-6 [SMD = −0.15, p = 0.09]. However, LCDs did not significantly decrease TNF-α [SMD = −0.02, p = 0.7] compared to LFDs. In conclusion, LCDs have a beneficial effect on markers of inflammation by decreasing CRP and IL-6; this effect has an association with weight loss. However, LCDs were not more effective than LFDs in decreasing TNF-α.

Consuming a hypocaloric high fat low carbohydrate diet for 12 weeks lowers C-reactive protein, and raises serum adiponectin and high density lipoprotein-cholesterol in obese subjects

Article

Sep 2013

High fat, low carbohydrate (HFLC) diets have become popular tools for weight management. We sought to determine the effects of a HFLC diet compared to a low fat high carbohydrate (LFHC) diet on the change in weight loss, cardiovascular risk factors and inflammation in subjects with obesity. Obese subjects (29.0-44.6kg/m(2)) recruited from Boston Medical Center were randomized to a hypocaloric LFHC (n=26) or HFLC (n=29) diet for 12weeks. The age range of subjects was 21-62years. As a percentage of daily calories, the HFLC group consumed 33.5% protein, 56.0% fat and 9.6% carbohydrate and the LFHC group consumed 22.0% protein, 25.0% fat and 55.7% carbohydrate. The change in percent body weight, lean and fat mass, blood pressure, flow mediated dilation, hip:waist ratio, hemoglobin A1C, fasting insulin and glucose, and glucose and insulin response to a 2h oral glucose tolerance test did not differ (P>0.05) between diets after 12weeks. The HFLC group had greater mean decreases in serum triglyceride (P=0.07), and hs-CRP (P=0.03), and greater mean increases in HDL cholesterol (P=0.004), and total adiponectin (P=0.045) relative to the LFHC. Secreted adipose tissue adiponectin or TNF-α did not differ after weight loss for either diet. Relative to the LFHC group, the HFLC group had greater improvements in blood lipids and systemic inflammation with similar changes in body weight and composition. This small-scale study suggests that HFLC diets may be more beneficial to cardiovascular health and inflammation in free-living obese adults compared to LFHC diets.

Comparative Effects of Carbohydrate versus Fat Restriction on Serum Levels of Adipocytokines, Markers of Inflammation, and Endothelial Function among Women with the Metabolic Syndrome: A Randomized Cross-Over Clinical Trial

Article

Sep 2013
ANN NUTR METAB

Background and aims: Despite the efficacy of low-carbohydrate diets in the management of metabolic syndrome (MetS), it remains unknown if these favorable effects are mediated through changes in inflammation and endothelial dysfunction. We aimed to assess the effects of moderate substitution of dietary fats for carbohydrates on serum levels of adipocytokines, inflammatory indices, and biomarkers of endothelial function among women with the MetS. Methods: In a randomized cross-over clinical trial, 30 overweight or obese (BMI >25) women with the MetS were randomly allocated to follow either a high-carbohydrate (HC) (60-65% carbohydrates, 20-25% fats) diet or a moderately restricted carbohydrate (MRC) (43-47% carbohydrate, 36-40% fats) diet, each for 6 weeks. After a 2-week washout period, individuals were switched to the alternate diet for an additional 6 weeks. In a fasted state, markers of inflammation [high-sensitivity C-reactive protein (hs-CRP), high-sensitivity interleukin-6 (hs-IL-6), high-sensitivity tumor necrosis factor-α (hs-TNF-α), and serum amyloid A (SAA)], endothelial function [E-selectin, serum intercellular adhesion molecule 1 (sICAM-1), and serum vascular cell adhesion molecule 1 (sVCAM-1)], and adipocytokines (leptin and adiponectin) were measured in both study arms at baseline and after 6 weeks. Results: Consumption of an HC diet was associated with increased levels of SAA (3.27 ± 1.22 μg/ml) and decreased levels of adiponectin (-1.68 ± 2.30 ng/ml), while consumption of an MRC diet did not result in such unfavorable effects. Serum concentrations of leptin were reduced by the HC diet (p = 0.02), while they were not affected by the MRC diet. Changes in serum leptin levels were not significant between the two diets (p = 0.09). Serum concentrations of hs-CRP, hs-TNF-α, and IL-6 were not influenced by either diet. No significant differences between the two diets were found in terms of their effect on sICAM-1 and sVCAM-1 concentrations. Adherence to both diets resulted in a 9 ng/ml decrease in serum E-selectin levels (p < 0.05 for both). Conclusions: Partial replacement of dietary carbohydrates by unsaturated fats prevents the increased levels of markers of systemic inflammation among women with the MetS.

Association between modifiable lifestyle factors and inflammatory markers in patients with metabolic syndrome

Article

Full-text available

Jul 2012

There is accumulating evidence suggesting that inflammation is the bridging link between cardiovascular disease and metabolic syndrome. Recent studies have shown a relationship between inflammatory markers and modifiable lifestyle factors including fitness, diet, exercise and smoking. We carried out a cross-sectional study of 195 patients with metabolic syndrome. Data on nutritional intake, physical activity level and smoking habits were collected through a questionnaire. Weight and body composition were determined and C-reactive protein and interluekin-6 concentrations were measured. C-reactive protein level had a significant association with body mass index (r = 0.18), adiposity (r = 0.23), smoking (r = 0.20), carbohydrate intake (r = 0.19) and saturated fatty acid (r = 0.20). Interluekin-6 concentration was significantly correlated with dietary carbohydrate (r = 0.15), saturated fatty acid (r = 0.15) and glycaemic load (r = 0.15). No association was observed between physical activity level and inflammatory markers.

Randomized controlled trials investigating the relationship between dietary pattern and high-sensitivity C-reactive protein: A systematic review

Article

Jun 2019
NUTR REV

Context: Elevated serum concentration of high-sensitivity C-reactive protein (hsCRP), a biomarker of systemic inflammation, is associated with increased risk for coronary heart disease (CHD) and cardiovascular events (CVEs). Because elevations in hsCRP often occur in parallel with elevations in low-density lipoproteins (LDLs) and both biomarkers are reduced by hydroxymethylglutaryl-CoA reductase inhibitors (ie, statin drugs), efforts to determine nonpharmacological treatments to lower hsCRP remain limited. Dietary modifications in particular are rarely discussed as viable clinical interventions yet merit investigation. Objective: This systematic review was performed to assess the relationship between dietary patterns and hsCRP among individuals enrolled in randomized controlled trials. Data sources: National Library of Medicine (ie, MEDLINE) and Google Scholar searches were performed using the search terms "C-reactive protein," "CRP," "dietary pattern," and/or "diet" to identify articles published between January 2000 and October 2017. Data extraction: Data were extracted and analyzed according to PRISMA guidelines. Identified abstracts were reviewed and cross-referenced for relevance to dietary pattern. Full-text manuscripts were then abstracted for their principal findings. Fifty-six manuscripts met inclusion criteria for detailed review. Results: Clinical trials of dietary interventions to reduce hsCRP are mixed in quality and findings. Several specific dietary patterns may reduce hsCRP, including low-fat, low-carbohydrate, Mediterranean, Portfolio, Paleolithic, and the Dietary Approaches to Stop Hypertension (DASH) diets. However, results were mixed for the majority of dietary patterns (eg, low-glycemic load diets). Conclusion: Information available to date suggests that a wide variety of dietary patterns may impact serum hsCRP, although studies are mixed in quality. The efficacy of dietary patterns for the treatment of elevated hsCRP as a strategy for primary prevention of CHD may be best elucidated in randomized clinical trials in healthy participants with elevated hsCRP but low or normal traditional risk factors, or by using more aggressive dietary modifications in high-risk patients. Given current incidence and prevalence of CHD risk factors, additional randomized controlled trials of this type are justified and needed.

The Effect of an Exercise and Diet Program on Fitness, Posture and Self Image in Women

Article

Full-text available

Jan 2010
J Appl Res Clin Exp Therapeut

One hundred seventeen female research subjects were involved in a single blinded randomized control study to assess the benefits of an exercise and diet program in restoring posture and balance and fitness in women who have given birth to 1or more children in the last 18 years. The program lasted for 2 months. There were 3 groups of subjects, an exercise group (E), a control group (C), and a pre pregnancy group (P). E, followed a diet involving exchanges for breakfast, lunch and dinner. The exercise involved a 10 minute abdominal exercise

Effect of Dietary Composition of Weight Loss Diets on High Sensitivity C-Reactive Protein: The Randomized POUNDS LOST Trial

Article

Apr 2013
OBESITY

Objective: Overweight and obesity are associated with increased high-sensitivity C-reactive protein (hsCRP) levels. The purpose of this study was to determine if weight loss diets differing in fat, protein, or carbohydrate composition differentially reduce hsCRP. Design and methods: POUNDS (preventing overweight using novel dietary strategies) LOST was a 2-year trial of overweight and obese adults randomly allocated to one of four weight loss diets with targeted percentages of energy derived from fat, protein, and carbohydrates (20, 15, 65%; 20, 25, 55%; 40, 15, 45%; 40, 25, 35%, respectively). hsCRP was measured at baseline, 6, and 24 months among 710 participants, and adiposity as measured by dual X-ray absorptiometry (N = 340) or abdominal computed tomography (N = 126) was correlated with hsCRP change. Results: At 6 months, hsCRP was reduced in all trial participants by -24.7% (Interquartile range (IQR) +7%, -50%), weight by -6.7% (IQR -3%, -11%), and waist circumference by -6.0% (IQR -3%, -10%) (all P < 0.002), with no significant differences according to dietary composition. The percent change in hsCRP at 6 and 24 months correlated modestly with change in weight, waist circumference, fasting insulin, fasting glucose, HOMA, and most lipid levels. Reductions in hsCRP persisted despite ∼ 50% regain of weight by 24 months. The percent change in hsCRP at 24 months significantly correlated with changes in total body fat (r = 0.42), total abdominal adiposity (r = 0.52), subcutaneous abdominal adiposity (r = 0.52), visceral adiposity (r = 0.47), and hepatic tissue density (r = -0.34) (all P < 0.0006). Conclusion: Weight loss decreased hsCRP by similar magnitude, irrespective of dietary composition. Clinicians concerned about inflammation and cardiovascular risk should recommend weight loss diets most likely to succeed for their patients.

Effect Of Ala54thr Polymorphism Of Fabp2 On Anthropometric And Biochemical Variables In Response To A Moderate-fat diet

Article

Full-text available

Jul 2012

Objective: To analyze the effect of the fatty acid-binding protein (FABP2) gene Ala54Thr polymorphism on anthropometric and biochemical variables in response to a moderate-fat diet in overweight or obese subjects. Methods: One hundred nine subjects with a body mass index ≥ 25 kg/m(2) were studied. Participants underwent a dietary intervention that consisted of 30% fat (saturated fat <7% of total calories), 15% protein, and 55% carbohydrates. The FABP2 genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism. Anthropometric and biochemical data were measured at baseline, 1 mo, and 2 mo of nutritional intervention. Results: The mean age was 38.6 ± 11.3 y and the mean body mass index 32.7 ± 6.1 kg/m(2), with 20 men (18%) and 89 women (82%). Fifty-three patients (48.6%) had genotype Ala54Ala (wild-type group) and 56 patients had genotype Ala54Thr/Thr54Thr (51.4%, mutant group). At baseline, no significant difference was found between the FABP2 genotypes groups, except for the carbohydrate intake and resting metabolic rate, which were higher in the Ala54Thr/Thr54Thr group (P < 0.05). At 2 mo, participants had lost 6.8% of their initial weight. The Ala54Thr/Thr54Thr group compared with the Ala54Ala group showed significant decreases in the parameters of weight (-7.5 versus -4.2 kg), body mass index (-2.1 versus -1.2 kg/m(2)), waist circumference (-7.6 versus -5.2 cm), waist-to-hip ratio (-0.04 versus -0.02), and C-reactive protein (-1.4 versus -0.76 mg/L), respectively (P < 0.05). After the resting metabolic rate was adjusted, the decreases in waist circumference, waist-to-hip ratio, and C-reactive protein remained significant between the two groups. Conclusions: This study showed that the Thr54 allele carriers responded better to a moderate-fat diet.

Rosuvastatin, inflammation, C-reactive Protein, JUPITER, and primary prevention of cardiovascular disease–a perspective

Article

Full-text available

Dec 2010

Richard Kones

The major public health concern worldwide is coronary heart disease, with dyslipidemia as a major risk factor. Statin drugs are recommended by several guidelines for both primary and secondary prevention. Rosuvastatin has been widely accepted because of its efficacy, potency, and superior safety profile. Inflammation is involved in all phases of atherosclerosis, with the process beginning in early youth and advancing relentlessly for decades throughout life. C-reactive protein (CRP) is a well-studied, nonspecific marker of inflammation which may reflect general health risk. Considerable evidence suggests CRP is an independent predictor of future cardiovascular events, but direct involvement in atherosclerosis remains controversial. Rosuvastatin is a synthetic, hydrophilic statin with unique stereochemistry. A large proportion of patients achieve evidence-based lipid targets while using the drug, and it slows progression and induces regression of atherosclerotic coronary lesions. Rosuvastatin lowers CRP levels significantly. The Justification for Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial was designed after the observation that when both low density lipoprotein and CRP were reduced, patients fared better than when only LDL was lowered. Advocates and critics alike acknowledge that the benefits of rosuvastatin in JUPITER were real. After a review, the US Food and Drug Administration extended the indications for rosuvastatin to include asymptomatic JUPITER-eligible individuals with one additional risk factor. The American Heart Association and Centers of Disease Control and Prevention had previously recognized the use of CRP in persons with "intermediate risk" as defined by global risk scores. The Canadian Cardiovascular Society guidelines went further and recommended use of statins in persons with low LDL and high CRP levels at intermediate risk. The JUPITER study focused attention on ostensibly healthy individuals with "normal" lipid profiles and high CRP values who benefited from statin therapy. The backdrop to JUPITER during this period was an increasing awareness of a rising cardiovascular risk burden and imperfect methods of risk evaluation, so that a significant number of individuals were being denied beneficial therapies. Other concerns have been a high level of residual risk in those who are treated, poor patient adherence, a need to follow guidelines more closely, a dual global epidemic of obesity and diabetes, and a progressively deteriorating level of physical activity in the population. Calls for new and more effective means of reducing risk for coronary heart disease are intensifying. In view of compelling evidence supporting earlier and aggressive therapy in people with high risk burdens, JUPITER simply offers another choice for stratification and earlier risk reduction in primary prevention patients. When indicated, and in individuals unwilling or unable to change their diet and lifestyles sufficiently, the benefits of statins greatly exceed the risks. Two side effects of interest are myotoxicity and an increase in the incidence of diabetes.

Intermittent Energy Restriction Combined with a High-Protein/Low-Protein Diet: Effects on Body Weight, Satiety, and Inflammation: A Pilot Study

Article

Full-text available

May 2023

Intermittent energy restricted (IER) diets have become popular as a body weight management approach. In this pilot study, we investigated if an IER diet would reduce systemic inflammation and if maintaining an elevated protein level while on an IER diet would enhance satiety. Six healthy women, aged 33–55 years with a BMI of 27–33 kg/m2, were randomized to first adhere to either a low- or high-protein IER diet using whole foods for three weeks. They then returned to their regular diets for a week, after which they adhered to the second diet for three weeks. Each test diet consisted of three low-energy intake days followed by four isocaloric energy intake days. The diets differed only in protein content. High-sensitivity C-reactive protein (hs-CRP), glucose, satiety, body weight, and waist circumference were measured at the beginning and end of each dietary intervention. Most participants showed reductions in hs-CRP levels from baseline on both IER diets but reported greater satiety when adhering to the higher protein IER diet. Overall, the IER diets reduced body weight and appeared to decrease inflammation in these overweight women, and the higher protein version enhanced satiety, which may lead to greater long-term dietary adherence.

Is oxidative stress involved in the hepatic inflammatory response to apical periodontitis? A comparative study in normal and hyperlipidemic rat

Article

Full-text available

Feb 2023
INT ENDOD J

Aim: To explore the involvement of oxidative stress (OS) in the hepatic inflammation induced by apical periodontitis (AP). Periapical, systemic, and hepatic reaction to AP under hyperlipidemia was also investigated. Methodology: 16 male Sprague-Dawley rats were fed with a hyperlipidemic diet (HD) whereas another 16 rats with a normal diet (ND). After 9 weeks, the first molars of the right maxilla and mandible of 8 HD and 8 ND rats were exposed to induce AP (ND, ND+AP, HD, and HD+AP group). After five weeks, rats were euthanized and the haematological tissue was collected directly from the heart, and serum levels of inflammatory cytokines were measured. Liver tissue was analyzed by haematoxylin-eosin and Masson staining, and reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect mRNA expression of inflammatory cytokines. Serum, periapical, and hepatic OS parameters including total oxidant status (TOS), total antioxidant capacity (TAOC), and oxidative stress index (OSI) were measured by enzyme-linked immunosorbent assay (ELISA). The area of AP lesion in the right maxilla or mandible was radiographically assessed. Student's t-test was performed on the periapical data. A one-way analysis of variance and the Kruskal-Wallis test were analyzed for others. Result: The HD+AP group had a larger AP lesion in the maxilla, compared with the ND+AP group (P<0.05). The ND+AP group presented higher serum interleukin (IL)-18, IL-1β, TOS, OSI levels, lower serum TOAC levels, higher hepatic tumor necrosis factor (TNF)-α mRNA expression, and higher hepatic TOS, and OSI levels, compared with the ND group (P<0.05). The HD+AP group had lower serum IL-4 level, higher serum IL-1β level, and higher hepatic IL-6 and transforming growth factor (TGF) -β1 mRNA expression, compared with the HD group (P<0.05). Conclusion: AP could activate systemic and liver inflammation by promoting serum IL-18, 1L-1β, TOS, OSI expression, enhancing hepatic TOS, OSI expression, and inhibiting serum TOAC expression. AP under hyperlipidemia led to more profound periapical bone destruction in the maxilla and elicit systemic and liver inflammatory responses through elevating serum levels of IL-1β, descending serum IL-4 level, and improving hepatic IL-6, TGF-β1 expression.

Low-carbohydrate and ketogenic diets: A scoping review of neurological and inflammatory outcomes in human studies and their relevance to chronic pain

Article

Full-text available

Apr 2022

Dietary restriction of carbohydrate has been demonstrated to be beneficial for nervous system dysfunction in animal models and may be beneficial for human chronic pain. The purpose of this review is to assess the impact of a low-carbohydrate/ketogenic diet on the adult nervous system function and inflammatory biomarkers to inform nutritional research for chronic pain. An electronic data base search was carried out in May 2021. Publications were screened for prospective research with dietary carbohydrate intake <130g/day and duration of ≥2 weeks. Studies were categorised into those reporting adult neurological outcomes to be extracted for analysis and those reporting other adult research outcomes Both groups were screened again for reported inflammatory biomarkers. From 1548 studies there were 847 studies included. Sixty-four reported neurological outcomes with 83% showing improvement. Five hundred and twenty-three studies had a different research focus (metabolic n=394, sport/performance n=51, cancer n=33, general n=30, neurological with non-neuro outcomes n=12, or gastrointestinal n=4). The second screen identified 63 studies reporting on inflammatory biomarkers with 71% reporting a reduction in inflammation. The overall results suggest a favourable outcome on the nervous system and inflammatory biomarkers from a reduction in dietary carbohydrates. Both nervous system sensitisation and inflammation occur in chronic pain and the results from this review indicate it may be improved by low-carbohydrate nutritional therapy. More clinical trials within this population are required to build on the few human trials that have been done.

Dietary Carbohydrate Quality and Quantity and Risk of Breast Cancer among Iranian Women

Article

Jun 2021

Objective This study investigated the association between quality and quantity of carbohydrate by assessing low carbohydrates diet score (LCDS), carbohydrate quality score (CQI), glycemic index (GI), dietary glycemic load (GL), and dietary carbohydrate intake, and risk of breast cancer (BrCa) among Iranian women. Methods This hospital-based case-control study was carried out in the Cancer Research Center of Imam Khomeini hospital, Iran. We included One hundred and fifty newly diagnosed BrCa cases and one hundred and fifty healthy controls in this study. Socio-demographic and dietary data and anthropometric measures were recorded. Results We found that a higher CQI than a lower score was associated with a decrease in odds of BrCa (P = 0.04). After adjusting for potential confounders, we observed that CQI was not associated with BrCa development (P = 0.05). An increase in odds of BrCa among women in the highest tertiles of GL (P = 0.12), GI (P = 0.48), and dietary carbohydrate intake (P = 0.06) was seen, which was not statistically significant. There was also a non-significant lower chance of having BrCa with adherence to the LCDS (P = 0.09). Conclusion Our findings suggest that CQI was not related to BrCa risk among Iranian women. This relation deserves to be investigated in prospective studies.

Adherence to the low carbohydrate diet and the risk of breast Cancer in Iran

Article

Full-text available

Dec 2019
Nutr J

Background: Previous studies on the link between macronutrients and breast cancer have mostly focused on individual macronutrients rather than their combination. This study investigates the association between adherence to a low carbohydrate diet and odds of breast cancer among women. Methods: This hospital-based case-control study was carried out on 412 women with pathologically confirmed breast cancer within the past year and 456 apparently healthy controls that were matched in terms of age and residential place. Dietary data was collected using a 168-item validated FFQ. Participants were classified in terms of quintiles of percentages of energy intake from carbohydrates, proteins, and fats. Then, individuals in the highest quintile of fat and protein intake were given a score of 5 and those in the lowest quintile of these macronutrients were given a score of 1. Participants in the other quintiles of these macronutrients were given the corresponding score. In terms of carbohydrate intake, those in the highest quintile received a score of 1 and those in the lowest quintile received 5. The scores were then summed up to calculate the total low carbohydrate diet (LCD) score, which varied from 3 to 15. A higher score meant greater adherence to a low carbohydrate diet. Results: The mean age of study participants was 45.2 y and mean BMI was 28.4 kg/m2. Mean LCD score of participants was 8.9 ± 2.5 (8.9 ± 2.6 in cases and 9.0 ± 2.5 in controls). Although no significant association was observed between adherence to the LCD score and odds of breast cancer in the study population, a trend toward significant positive association was seen between consumption of LCD and odds of breast cancer in postmenopausal women; after controlling for several potential confounders, individuals in the third quartile of LCD score were 1.94 times more likely to have breast cancer than those in the lowest quartile (95% CI: 1.00, 3.76). This association strengthened after controlling for dietary variables (2.50; 1.18-5.32). Even after further adjustment for BMI, this association remained significant (2.64, 1.23-5.67). No significant relationship was observed in premenopausal women, either before or after controlling for confounders. Conclusion: Adherence to LCD may be associated with increased odds of breast cancer in postmenopausal women. Prospective cohort studies are needed to confirm these findings.

A Pilot Low-Inflammatory Dietary Intervention to Reduce Inflammation and Improve Quality of Life in Patients With Familial Adenomatous Polyposis: Protocol Description and Preliminary Results

Article

Full-text available

May 2019
INTEGR CANCER THER

Patients with familial adenomatous polyposis (FAP) depend on a lifelong endoscopic surveillance programme and prophylactic surgery, and usually suffer nutritional problems. Intestinal inflammation has been linked to both FAP and colorectal cancer. Epidemiological studies show a relationship between diet and inflammation. Preventive dietary recommendations for FAP patients are so far lacking. We have designed a nonrandomized prospective pilot study on FAP patients to assess whether a low-inflammatory diet based on the Mediterranean diet principles and recipes, by interacting with the microbiota, reduces gastrointestinal markers of inflammation and improves quality of life. This report describes the scientific protocol of the study and reports the participants’ adherence to the proposed dietary recommendations. Thirty-four FAP patients older than 18 years, bearing the APC pathogenic variant, who underwent prophylactic total colectomy with ileo-rectal anastomosis were eligible into the study. During the 3-month dietary intervention, they reported improvements in their consumption of Mediterranean foods (vegetables, fruits, fish, and legumes), and a reduction in pro-inflammatory foods (red/processed meat and sweets); this led to a significant increase in their adherence to the Mediterranean diet. The improvement was accompanied by a decrease in the number of diarrhoeal discharges. These preliminary results are encouraging with regard to feasibility, dietary outcome measures, and safety.

Dietary fat intake associated with bone mineral density among visfatin genotype in obese people

Article

Jan 2018

Osteoporosis and adipose tissue are closely related with many contradictions. Visfatin is an adipokine that is related to osteoporosis and adiposity. This nutrigenomics study examined the interaction between visfatin genotypes and dietary fat intake, with regard to bone mineral density (BMD) among an obese population. In this cross-sectional study, 336 subjects were enrolled; the mean age was 38·25 ( sd 11·69) years and the mean BMI was 31·79 ( sd 4·77) kg/m ² . Laboratory measurements were lipid profile, insulin and fasting blood sugar. Bone density measurements were assessed by dual-energy X-ray absorptiometry. Dietary data were collected through a 3-d 24-h dietary recall. Genotyping for visfatin gene SNP ( rs2110385 ) was performed by the PCR-restriction fragment length polymorphism method. The frequency of GG, GT and TT genotypes were 33·92 48·51 and 17·54 %, respectively, and 86·6 % of participants were women. The results showed that subjects with TT genotypes had significantly higher lumbar BMD, T score and z score ( P <0·0001). After categorisation by percentage of fat intake (30 % of total energy content as a cut-off point), no interaction was found, but when categorised by fat types, we found an interaction between visfatin genotypes and dietary PUFA intake in terms of the hip T score and z score ( P =0·043, B = −0·08; P =0·04, B = −0·078, respectively). There was a significant relationship between high PUFA intake and lower energy and protein intake. When participants were categorised by median PUFA intake (22·8 g), it was concluded that subjects with GG genotype who had high PUFA-intake diets had lower hip z scores and T scores, unlike the other genotypes.

Reducing Cardiovascular Disease Risk in Youth with Type 2 Diabetes Through Dietary Carbohydrate Restriction: Clinical and Molecular Perspectives

Article

Full-text available

Jan 2017

Every year, increasing numbers of children and adolescents are diagnosed with type 2 diabetes. Compared to older adults with type 2 diabetes, youth have more difficulty controlling their glycemia and are faced with a much greater risk for cardiovascular disease. Although pharmaceutical options for management of diabetes and its co-morbidities are limited for youth, studies in adults as well as adolescents indicate that a low-carbohydrate diet may be an alternative way to reduce body weight and control blood sugar levels. To assess whether low-carbohydrate diets can also reduce the cardiovascular disease risk that accompanies type 2 diabetes in youth, we discuss the impact of both ketogenic and non-ketogenic low-carbohydrate diets on indicators of cardiovascular disease. This discussion includes not only traditional cardiovascular disease risk markers such as dyslipidemia, but also other factors that are associated with obesity and type 2 diabetes in adolescents such as interleukin-6, C-reactive protein and endothelial dysfunction. We also explore the practicalities involved in adopting and adhering to a low-carbohydrate diet such as the ketogenic diet, discussing its effects on satiety, its cultural adaptability and the types of foods that it emphasizes. The proficiency with which low-carbohydrate diets can reduce excess body weight, improve lipid profiles and attenuate inflammation without restricting calories or decreasing satiety, suggests that they may be an effective tool to reduce cardiovascular disease risk in youth with type 2 diabetes.

Comparative effects of carbohydrate versus fat restriction on metabolic profiles, biomarkers of inflammation and oxidative stress in overweight patients with Type 2 diabetic and coronary heart disease: A randomized clinical trial

Article

Full-text available

Nov 2016

BACKGROUND This study was conducted to establish the comparative effects of carbohydrate versus fat restriction on metabolic indices in Type 2 diabetic (T2D) patients with coronary heart disease (CHD). METHODS This randomized, clinical trial was done among 56 overweight persons with T2D and CHD aged 40-85 years old. The patients were randomly allocated to take either a high-carbohydrate (HC) diet (60-65% carbohydrates and 20-25% fats) (n = 28) or a restricted carbohydrate (RC) diet (43-49% carbohydrate and 36-40% fats) (n = 28) for 8 weeks to determine metabolic status. RESULTS After 8 weeks of treatment, RC diet decreased fasting plasma glucose (FPG) (−11.5 ± 28.3 vs. +7.0 ± 26.9 mg/dl, P = 0.010) and high-sensitivity C-reactive protein (hs-CRP) (−564.3 ± 1280.1 vs. +286.1 ± 1789.2 ng/ml, P = 0.040) compared with a HC diet. Moreover, compared with a HC diet, RC diet increased total antioxidant capacity (TAC) (+274.8 ± 111.5 vs. +20.2 ± 82.5 mmol/l, P < 0.001) and glutathione (GSH) levels (+51.6 ± 111.5 vs. −32.6 ± 88.5 µmol/l, P = 0.003). No significant alterations between the two groups were found in terms of their effect on other metabolic profiles. CONCLUSION RC diet in overweight T2D with CHD had beneficial effects on FPG, hs-CRP, TAC, and GSH values.

Effect of Nutritional Status and Dietary Patterns on Human Serum C-Reactive Protein and Interleukin-6 Concentrations

Article

Full-text available

Nov 2015

The inflammatory process plays an important role in the pathogenesis of many chronic diseases, such as cardiovascular diseases, diabetes mellitus type 2, and metabolic syndrome. Serum C-reactive protein (CRP) and interleukin-6 (IL-6) are widely tested inflammatory markers involved in the development of these diseases. Several studies indicate a relation between nutritional status and the concentrations of human high-sensitivity CRP and IL-6. Similarly, the role of diet in reducing inflammation and thereby modulating the risk of non-communicable diseases is supported by numerous studies. This review focuses on the effects of the selected nutrition models in humans on the concentrations of CRP and IL-6. It seems that the Mediterranean diet model is most effective in inhibiting inflammation. The Dietary Approaches to Stop Hypertension model and the plant nutrition model also have proven to be beneficial. The data on low-fat and low-carbohydrate diets are inconclusive. Comprehensive studies are necessary, taking into account the cumulative effect of dietary and other factors on the inflammatory process.

The Effects of a Low-Carbohydrate Diet vs. a Low-Fat Diet on Novel Cardiovascular Risk Factors: A Randomized Controlled Trial

Article

Full-text available

Sep 2015

Increasing evidence supports a low-carbohydrate diet for weight loss and improvement in traditional cardiovascular disease (CVD) markers. Effects on novel CVD markers remain unclear. We examined the effects of a low-carbohydrate diet (<40 g/day; n = 75) versus a low-fat diet (<30% kcal/day from total fat, <7% saturated fat; n = 73) on biomarkers representing inflammation, adipocyte dysfunction, and endothelial dysfunction in a 12 month clinical trial among 148 obese adults free of diabetes and CVD. Participants met with a study dietitian on a periodic basis and each diet group received the same behavioral curriculum which included dietary instruction and supportive counseling. Eighty percent of participants completed the intervention. At 12 months, participants on the low-carbohydrate diet had significantly greater increases in adiponectin (mean difference in change, 1336 ng/mL (95% CI, 342 to 2330 ng/mL); p = 0.009) and greater decreases in intercellular adhesion molecule-1 concentrations (-16.8 ng/mL (-32.0 to -1.6 ng/mL); p = 0.031) than those on the low-fat diet. Changes in other novel CVD markers were not significantly different between groups. In conclusion, despite the differences in weight changes on diets, a low-carbohydrate diet resulted in similar or greater improvement in inflammation, adipocyte dysfunction, and endothelial dysfunction than a standard low-fat diet among obese persons.

Minimal Impact of Nutrition Education and Fruit and Vegetable Consumption on Biomarkers of Inflammation and Oxidative Stress

Article

Full-text available

Jan 2015

Effects of Dietary Fat and Saturated Fat Content on Liver Fat and Markers of Oxidative Stress in Overweight/Obese Men and Women under Weight-Stable Conditions

Article

Full-text available

Nov 2014

Dietary fat and oxidative stress are hypothesized to contribute to non-alcoholic fatty liver disease and progression to steatohepatitis. To determine the effects of dietary fat content on hepatic triglyceride, body fat distribution and markers of inflammation and oxidative stress, overweight/obese subjects with normal glucose tolerance consumed a control diet (CONT: 35% fat/12% saturated fat/47% carbohydrate) for ten days, followed by four weeks on a low fat (LFD (n = 10): 20% fat/8% saturated fat/62% carbohydrate) or high fat diet (HFD (n = 10): 55% fat/25% saturated fat/27% carbohydrate). Hepatic triglyceride content was quantified by MRS and abdominal fat distribution by MRI. Fasting biomarkers of inflammation (plasma hsCRP, IL-6, IL-12, TNFα, IFN-γ) and oxidative stress (urinary F2-α isoprostanes) were measured. Body weight remained stable. Compared to the CONT, hepatic triglyceride decreased on the LFD (mean (95% CI): change -2.13% (-3.74%, -0.52%)), but did not change on the HFD and there was no significant difference between the LFD and HFD. Intra-abdominal fat did not change significantly on either diet, but subcutaneous abdominal fat increased on the HFD. There were no significant changes in fasting metabolic markers, inflammatory markers and urinary F2-α isoprostanes. We conclude that in otherwise healthy overweight/obese adults under weight-neutral conditions, a diet low in fat and saturated fat has modest effects to decrease liver fat and may be beneficial. On the other hand, a diet very high in fat and saturated fat had no effect on hepatic triglyceride or markers of metabolism, inflammation and oxidative stress.

The use of low-carbohydrate diet in type 2 diabetes - benefits and risks

Article

Full-text available

Jun 2014
ANN AGR ENV MED

The pharmacological treatment of type 2 diabetes is increasingly being supported by the recommendation of an appropriate diet. The purpose of this study is to identify the potential benefits and risks arising from the use of one of the modern models of low-carbohydrate diet in patients with type 2 diabetes. Research shows that diet can favourably affect the health of diabetic patients. It has been shown that diet affects positively the concentration of blood glucose, glycosylated haemoglobin, and also contributes to the reduction of insulin taken in the course of drug therapy. At the same time, short-term studies have demonstrated a positive relationship of nutrition with reduction in body weight, as well as favourable changes in lipid profile of HDL cholesterol and levels of triglyceride. Attention is also drawn to the negative health effects of a low-carbohydrate diet; these include an increased risk of mineral deficiency, hypovitaminosis and reduced intake of dietary fibres. This diet may be associated with very high levels of protein which, in turn, raises the risk of renal dysfunction and the appearance of irregularities in the water and electrolyte balance. The impact of changes in the skeletal system and the development of osteopenia and osteoporosis is also observed. Besides the positive impact of this model of diet on the lipid profile parameters, its use significantly increases the risk of adverse changes in other markers predisposing to atherosclerosis occurring in individuals with type 2 diabetes. In composing a nutrition model for diabetes patients, both the benefits and potential risks of a low-carbohydrate diet should therefore take into account. At the same time, it is important to individualize the diet used, based on the current state of health, used pharmacological treatments, as well as taking into account the individual characteristics of the patient.

Increasing the Percentage of Energy from Dietary Sugar, Fats, and Alcohol in Adults Is Associated with Increased Energy Intake but Has Minimal Association with Biomarkers of Cardiovascular Risk

Article

Full-text available

Aug 2013
J NUTR

The optimal diet composition to prevent obesity and its complications is unknown. Study aims were to determine the association of diet composition with energy intake, homeostatic model assessment-insulin resistance (HOMA-IR), and C-reactive protein (CRP). Data were from the NHANES for eligible adults aged 20-74 y from 2005 to 2006 (n = 3073). Energy intake and diet composition were obtained by dietary recall. HOMA-IR was calculated from fasting insulin and glucose concentrations, and CRP was measured directly. Changes for a 1-point increase in percentage of sugar, saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), and alcohol were determined across their means in exchange for a 1-point decrease in percentage of nonsugar carbohydrates. Regression analyses were performed, and means ± SEs were estimated. Increasing the percentage of sugar was associated with increased energy intake in men (23 ± 5 kcal; P < 0.001) and women (12 ± 3 kcal; P = 0.002). In men, increasing percentages of SFAs (58 ± 13 kcal; P = 0.001) and PUFAs (66 ± 19 kcal; P < 0.001) were associated with increased energy intake. In women, increasing percentages of SFAs (27 ± 10 kcal; P = 0.02), PUFAs (43 ± 6 kcal; P < 0.001), and MUFAs (36 ± 13 kcal; P = 0.01) were associated with increased energy intake. Increasing the percentage of alcohol was associated with increased energy intake in men (38 ± 7 kcal; P < 0.001) and women (25 ± 8 kcal; P = 0.001). Obesity was associated with increased HOMA-IR and CRP in both genders (all P ≤ 0.001). Increasing PUFAs was associated with decreasing CRP in men (P = 0.02). In conclusion, increasing the percentage of calories from sugar, fats, and alcohol was associated with substantially increased energy intake but had minimal association with HOMA-IR and CRP.

Simple Diet Messages that Improve Overall Dietary Quality

Article

Sep 2008
J AM DIET ASSOC

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

Article

Full-text available

May 2013
Nutr J

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.

Nutrition and oxidative stress: A systematic review of human studies

Article

Nov 2012
INT J FOOD SCI NUTR

Oxidative stress (OS) - defined as the imbalance between free radical production and antioxidant defences - is a condition associated with chronic-degenerative disease, such as cancer, metabolic and disease cardiovascular diseases (CVDs). Several studies have shown that diet and some of its components could influence the intensity of OS damage. The aim of this review was to critically examine some pieces of evidence from observational and intervention study in human beings to assess whether diet and its components can really modify OS in vivo. Furthermore, we tried to find out the possible mechanism behind this association. We considered all studies in MEDLINE which fitted with the following criteria: (1) adult subjects who were healthy or affected by metabolic disease and CVDs; (2) no food supplements, pillows, powder but only common foods and beverages and (3) OS assessment with well-known and validated in vivo biomarkers.

Effects of Dietary Composition on Energy Expenditure During Weight-Loss Maintenance

Article

Jun 2012
J Am Med Assoc

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.

Effect of diet-induced weight loss on inflammatory cytokines in obese women

Article

Full-text available

Jun 2012
J ENDOCRINOL INVEST

Background: Obesity is associated with lowgrade systemic inflammation which has been linked to the increased risk of cardiovascular disease and Type 2 diabetes in obese patients. Aim: To evaluate changes in pro/anti-inflammatory adipocytokines and metabolic profile after moderate diet-induced weight loss. Subjects and methods: Twenty-nine pre-menopausal obese women (body mass index ≥30 kg/m2) aged 21 to 54 years without diabetes, hypertension, or hyperlipidemia, were enrolled in this study. We measured anthropometric parameters, lipid and glucose profiles, interleukin (IL)-6, IL-10, and IL-18 in obese women, who then entered a medically supervised program aimed at reducing body weight by 10% or more. Obese women restricted their caloric intake (by 500-1000 kcal/day) and consumed 50 g/day of a fiber supplement (Slim Last Powder) for 12 weeks. Results: By completing the dietary intervention program, weight (Δ = -10.0%, p<0.0001), body mass index, waist circumference, triceps skinfold thickness, total cholesterol, triglyceride, and fasting plasma glucose significantly decreased, while HDL-cholesterol significantly increased. While plasma levels of IL-6 and IL-18 decreased by 27% after 12 weeks, no significant change was observed in circulating levels of IL-10. Conclusion: Our study suggests that an improved body composition induced by restriction of energy intake is associated with favorable serum concentrations of IL-6 and IL-18 in obese women. However, the anti-inflammatory IL-10 is not affected by a moderate weight decrease.

Effects on markers of inflammation and endothelial cell function of three ad libitum diets differing in type and amount of fat and carbohydrate: A 6-month randomised study in obese individuals

Article

Full-text available

Feb 2011
BRIT J NUTR

Diet is important for the prevention of CVD, and diets high in MUFA might be more cardioprotective than low-fat diets. We hypothesise that inflammation and endothelial cell function will be improved most favourably by a high-MUFA diet compared with a low-fat diet. This was tested in a parallel randomised intervention trial on overweight individuals (aged 28·2 (SD 4·6) years) assigned to a diet moderate in the amount of fat (35-45% of energy; >20% of fat as MUFA; MUFA diet, n 39), a low-fat (20-30% of energy) diet (LF diet, n 43) or a control diet (35 % of energy as fat, n 24) for 6 months after weight loss. Protein constituted 10-20 % of energy in all diets. Food was provided free of charge. Fasting blood samples were collected before and after the intervention and analysed for C-reactive protein (CRP), IL-6, intercellular adhesion molecule, von Willebrand factor (vWF) and tissue factor pathway inhibitor. vWF concentrations tended to fall on the LF diet (4·78 (SD 16·44) %; P = 0·07). Concentrations of IL-6 were reduced by the MUFA (0·37 (SD 0·74) pg/ml; P < 0·01) and LF (0·47 (SD 0·69) pg/ml; P < 0·001) diets, and CRP was reduced on all diets (MUFA: 0·48 (SD 1·93) mg/l (P < 0·01); LF: 1·46 (SD 2·89) mg/l (P < 0·001); control: 1·20 (SD 1·97) mg/l (P < 0·01)). No significant differences were observed between changes induced by the different diets. Our findings suggest that in overweight subjects after weight loss, the MUFA and LF diets have similar long-term effects on inflammation and endothelial cell function.

Diet and the development of atherosclerosis: a whole-diet approach from childhood to adulthood

Article

Vera Mikkilä

Cardiovascular diseases (CVDs) are the leading cause of mortality in the world. Studies of the impact of single nutrients on the risk for CVD have often provided inconclusive results, and recent research in nutritional epidemiology with a more holistic whole-diet approach has proven fruitful. Moreover, dietary habits in childhood and adolescence may play a role in later health and disease, either independently or by tracking into adulthood. The main aims of this study were to find childhood and adulthood determinants of adulthood diet, to identify dietary patterns present among the study population and to study the associations between long-term food choices and cardiovascular health in young Finnish adults. The study is a part of the multidisciplinary Cardiovascular Risk in Young Finns study, which is an ongoing, prospective cohort study with a 21-year follow-up. At baseline in 1980, the subjects were children and adolescents aged 3 to 18 years (n included in this study = 1768), and young adults aged 24 to 39 years at the latest follow-up study in 2001 (n = 1037). Food consumption and nutrient intakes were assessed with repeated 48-hour dietary recalls. Other determinations have included comprehensive risk factor assessments using blood tests, physical measurements and questionnaires. In the latest follow-up, ultrasound examinations were performed to study early atherosclerotic vascular changes. The average intakes showed substantial changes since 1980. Intakes of fat and saturated fat had decreased, whereas the consumption of fruits and vegetables had increased. Intake of fat and consumption of vegetables in childhood and physical activity in adulthood were important health behavioural determinants of adult diet. Additionally, a principal component analysis was conducted to identify major dietary patterns at each study point. A similar set of two major patterns was recognised throughout the study. The traditional dietary pattern positively correlated with the consumption of traditional Finnish foods, such as rye, potatoes, milk, butter, sausages and coffee, and negatively correlated with fruit, berries and dairy products other than milk. This type of diet was independently associated with several risk factors of CVD, such as total and low-density lipoprotein cholesterol, apolipoprotein B and C-reactive protein concentrations among both genders, as well as with systolic blood pressure and insulin levels among women. The traditional pattern was also independently associated with intima media thickness (IMT), a subclinical predictor of CVD, in men but not in women. The health-conscious pattern, predominant among female subjects, non-smokers and urbanites, was characterised by more health-conscious food choices such as vegetables, legumes and nuts, tea, rye, fish, cheese and other dairy products, as well as by the consumption of alcoholic beverages. This pattern was inversely, but less strongly, associated with cardiovascular risk factors. Tracking of the dietary pattern scores was observed, particularly among subjects who were adolescents at baseline. Moreover, a long-term high intake of protein concurrent with a low intake of fat was positively associated with IMT. These findings suggest that food behaviour and food choices are to some extent established as early as in childhood or adolescence and may significantly track into adulthood. Long-term adherence to traditional food choices seems to increase the risk for developing CVD, especially among men. Those with intentional or unintentional low fat diets, but with high intake of protein may also be at increased risk for CVD. The findings offer practical, food-based information on the relationship between diet and CVD and encourage further use of the whole-diet approach in epidemiological research. The results support earlier findings that long-term food choices play a role in the development of CVD. The apparent influence of childhood habits is important to bear in mind when planning educational strategies for the primary prevention of CVD. Further studies on food choices over the entire lifespan are needed. Sepelvaltimotaudin kliiniset oireet tulevat useimmiten esiin vasta keski-iässä tai sen jälkeen. Siihen johtavat ateroskleroottiset muutokset verisuonissa saattavat kehittyä jo lapsuudesta tai nuoruudesta alkaen. Ravinto on eräs tärkeimmistä sepelvaltimotaudin riskitekijöiden tasoa selittävistä tekijöistä. Useilla ravintotekijöillä on arveltu olevan yhteisvaikutuksia toistensa kanssa. Siksi ruokavalioon kokonaisuutena on viime aikoina alettu kiinnittää kasvavaa huomiota. Tämä tutkimus on osa laajaa LASERI-hanketta, jossa suomalaisten lasten, nuorten ja nuorten aikuisten sepelvaltimotaudin riskitekijöitä ja niiden muovautumista lapsuudesta aikuisuuteen on kartoitettu koko maan kattavassa monikeskustutkimuksessa. Tämä kansainvälisestikin ainutlaatuinen hanke käynnistettiin vuonna 1980, jolloin tutkittavat olivat 3-18-vuotiaita. Tämän tutkimuksen aineistona käytettiin kaikkiaan 1037 tutkittavalta toistuvasti vuosina 1980-2001 kerättyjä tietoja ruokavaliosta ja sepelvaltimotaudin riskitekijöiden tasosta. Vuonna 2001 saatiin ultraäänimittauksella tietoja kaulasuonten rakenteesta. Pitkän seurannan ansiosta tässä tutkimuksessa oli ainutlaatuinen mahdollisuus selvittää lapsuudesta aikuisuuteen muovautuvien ruokatottumusten roolia ateroskleroosin kehittymisessä. Kun ruokavaliota tarkasteltiin kokonaisuutena, aineistossa oli koko 21 vuoden seurannan ajan havaittavissa kaksi toisistaan poikkeavaa ruokavaliotyyppiä. Perinteiseen ruokavaliotyyppiin kuului runsas rukiin, perunoiden, maidon, voin, makkaran ja kahvin käyttö. Terveystietoiseksi nimetty toinen ruokavalio sisälsi runsaasti kasviksia, juureksia, teetä, ruista, kalaa, juustoa sekä aikusiällä myös alkoholijuomia. Nämä ruokavaliotyypit näyttivät pysyvän pääpiirteissään samanlaisina lapsuudesta aikuisuuteen. Pitkäaikainen perinteinen ruokavalio oli yhteydessä useisiin sepelvaltimotaudin riskitekijöihin, kuten korkeisiin LDL-kolesterolin, apolipoproteiini B:n ja C-reaktiivisen proteiinin tasoihin sekä naisilla myös kohonneeseen verenpaineeseen ja insuliinitasoon. Niillä miehillä, jotka käyttivät runsaasti perinteiselle ruokavaliolle tyypillisiä elintarvikkeita, havaittiin muita enemmän sepelvaltimotaudin riskiä ennustavaa valtimon seinämän paksuuntumista. Tätä paksuuntumista esiintyi myös niillä tutkittavilla, joiden ruokavalio sisälsi keskimääräistä enemmän proteiinia ja vähemmän rasvaa. Tutkimuksen tulokset vahvistavat näkemystä siitä, että lapsuudessa muotoutuvat ruokatottumukset jatkuvat usein aikuisuuteen. Perinteisen ruokavalion pitkäaikainen noudattaminen saattaa johtaa kohonneeseen riskiin sairastua sepelvaltimotautiin. Myös proteiinipitoinen ruokavalio ja samanaikainen, usein tietoinen, rasvan välttäminen saattaa lisätä sepelvaltimotaudin kehittymisen riskiä. Tämä tutkimus tarkastelee ruokavaliota kokonaisuutena ja tarjoaa siten käytännönläheistä tietoa ravinnon merkityksestä sepelvaltimotaudin kehittymisessä.

The effect of a ketogenic diet on inflammation-related markers: a systematic review and meta-analysis of randomized controlled trials

Article

Jan 2024

Context Despite the important role of inflammation-related factors on the occurrence of chronic diseases, there is still conflicting evidence about the effects of the ketogenic diet (KD) on these factors. Objective In order to obtain a better viewpoint, this study aimed to comprehensively investigate the effects of a KD on inflammation-related markers. Data Sources To find pertinent randomized controlled trials up to August 2023, databases including PubMed/Medline, Web of Science, Scopus, Cochrane Library, and Embase were searched. Data Extraction This study included all randomized controlled trials investigating the effects of a KD on C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-8, and IL-10 levels. Pooled weighted mean difference (WMD) and 95% confidence intervals (CIs) were achieved by random-effects model analysis for the best estimation of outcomes. Data Analysis Forty-four studies were included in this article. The pooled findings showed that a KD has an effect on lowering TNF-α (WMD: −0.32 pg/mL; 95% CI: −0.55, −0.09; P = 0.007) and IL-6 (WMD: −0.27 pg/mL; 95% CI: −0.52, −0.02; P = 0.036) compared with control groups. However, no significant effect was reported for others inflammation marker–related levels. The results of the subgroup analysis showed that, in trials following the KD for ≤8 weeks and in people aged ≤50 years, the reduction in TNF-α levels was significantly higher than in other groups. In addition, in people with a body mass index greater than 30 kg/m2 compared to a body mass index ≤30 kg/m2, IL-6 levels decreased to a greater extent after receiving the KD. Conclusions Consequently, adherence to a KD appears to improve some markers associated with inflammation, including TNF-α and IL-6.

C-Reactive Protein: Pathophysiology, Diagnosis, False Test Results and a Novel Diagnostic Algorithm for Clinicians

Article

Full-text available

Sep 2023

Dimitra S. Mouliou

The current literature provides a body of evidence on C-Reactive Protein (CRP) and its potential role in inflammation. However, most pieces of evidence are sparse and controversial. This critical state-of-the-art monography provides all the crucial data on the potential biochemical properties of the protein, along with further evidence on its potential pathobiology, both for its pentameric and monomeric forms, including information for its ligands as well as the possible function of autoantibodies against the protein. Furthermore, the current evidence on its potential utility as a biomarker of various diseases is presented, of all cardiovascular, respiratory, hepatobiliary, gastrointestinal, pancreatic, renal, gyneco-logical, andrological, dental, oral, otorhinolaryngological, ophthalmological, dermatological, musculoskeletal, neurological, mental, splenic, thyroid conditions, as well as infections, autoimmune-supposed conditions and neoplasms, including other possible factors that have been linked with elevated concentrations of that protein. Moreover, data on molecular diagnostics on CRP are discussed, and possible etiologies of false test results are highlighted. Additionally, this review evaluates all current pieces of evidence on CRP and systemic inflammation, and highlights future goals. Finally, a novel diagnostic algorithm to carefully assess the CRP level for a precise diagnosis of a medical condition is illustrated.

Altern messen – des Alterungsprozesses

Chapter

Jan 2022

Zumeist meinen wir mit Alter unser chronologisches Alter, also die verstrichene Zeit seit der Geburt. Es gibt aber auch ein biologisches Alter, welches die Geschwindigkeit misst, mit der Zellen und Gewebe altern. Diese beiden Zahlen stimmen meistens nicht überein. Wir alle kennen Menschen, die für ihr Alter jung aussehen oder die vorzeitig gealtert zu sein scheinen, und selbst bei einem Individuum können verschiedene Körperteile unterschiedlich schnell altern. Um zu bestimmen, ob das gemessene biologische Alter mit dem Erwarteten laut Bevölkerungsschnitt übereinstimmt, arbeiten die Forscher an Modellen, um dieses möglichst exakt zu bestimmen.

The Pros and Cons of Low Carbohydrate and Ketogenic Diets in the Prevention and Treatment of Cancer

Article

Full-text available

Feb 2021

Ketogenic diets are low carbohydrate (CHO), high fat diets that are currently very popular for weight loss. Since cancer cells typically consume far more glucose than normal cells, low CHO diets are currently being considered as possible therapeutic regimens to manage cancer. However, our understanding of the safety and efficacy of such CHO-restricted diets in the prevention and treatment of cancer is still in its infancy. In this perspective we provide an overview of the current state of knowledge regarding the use of low CHO diets in the prevention and treatment of cancer. We also highlight the gaps in our knowledge regarding the potential usefulness of low CHO diets in cancer. While pre-clinical rodent studies have provided convincing evidence that CHO restriction may be effective in reducing cancer growth, there has not been sufficient attention given to the effect of these low CHO diets, that are often high in fats and low in soluble fiber, on inflammation. This is important, given that different fats have distinct effects on inflammation. As well, we demonstrate that short chain fatty acids, which are produced via the fermentation of fiber by our gut microbiome, have more anti-inflammatory properties than β-hydroxybutyrate, a ketone body produced during nutritional ketosis that is touted to have anti-inflammatory activity. Since chronic inflammation is strongly associated with cancer formation, defining the type of fats in low CHO diets may contribute to our understanding of whether these diets may work simply by reducing glucose bioavailability, or via modulation of inflammatory responses.

Effects of luteolin on chemical induced colon carcinogenesis in high fat diet-fed obese mouse

Article

Full-text available

Feb 2018

Purpose: Colorectal cancer, which is one of the most commonly diagnosed cancers in developing and developed countries, is highly associated with obesity. The association is largely attributed to changes to western style diets in those countries containing high-fat and high-energy. Luteolin (LUT) is a known potent inhibitor of inflammation, obesity, and cancer. In this study, we investigated the effects of LUT on chemical-induced colon carcinogenesis in high fat diet (HFD)-fed obese mice. Methods: Five-week-old male C57BL/6 mice received a single intraperitoneal injection of azoxymethane (AOM) at a dose of 12.5 mg/kg body weight. Mice were then divided into four groups (n = 10) that received one of the following diets for 11 weeks after the AOM injection: normal diet (ND); HFD; HFD with 0.0025% LUT (HFD LL); HFD with 0.005% LUT (HFD HL). One week after AOM injection, animals received 1~2% dextran sodium sulfate in their drinking water over three cycles consisting of five consecutive days each that were separated by 16 days. Results: Body weight, ratio of colon weight/length, and tumor multiplicity increased significantly in the HFD group compared to the ND group. Luteolin supplementation of the HFD significantly reduced the ratio of colon weight/length and colon tumors, but not body weight. The levels of plasma TNF-? and colonic expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 protein increased in response to HFD, but were suppressed by LUT supplementation. Immunohistochemistry analysis also showed that iNOS expression was decreased by LUT. Conclusion: Consumption of LUT may reduce the risk of obesity-associated colorectal cancer by suppression of colonic inflammation.

Edible mushrooms: Potential role in weight regulation

Article

Feb 2012

Mushrooms are a class of " macrofungi" which in recent years have gained popularity among general consumers and the scientific community. Edible mushrooms have been shown to possess high nutritive value, and are being considered as " nutraceuticals" due to their potential health benefits. In vitro and in vivo studies suggest that bioactive compounds in mushrooms have immunomodulatory, anti-inflammatory, anti-oxidative, lipid lowering and anti-tumor effects. Some research findings suggest that edible mushroom consumption is associated with prevention of cardiovascular diseases. Many of these health benefits can be attributed to the nutrient profile of the mushrooms, which include protein, B-vitamins, minerals, along with low fat content. In addition, bioactive compounds like polyphenols and flavonoids present in mushrooms may contribute to health benefits. Weight management is a growing concern for all segments of the U.S. population. Moreover, recent statistics provide compelling evidence that overweight and obesity are on the rise not only among adults, but also in children younger than twelve years of age. This growing trend in overweight and obesity imposes major health, economic and social burdens worldwide. While genetic, biologic and social factors are responsible to a great extent, many individuals engage in dietary behaviors that put them at risk of weight gain. On the intake side of the energy balance equation, high intake of energy-dense foods is largely responsible for the problem of positive energy balance, and the resulting epidemic of overweight and obesity in the U.S. Energy regulation is complex, but there is evidence that humans have limited ability to regulate food intake in response to changes in energy density. One obvious method of preventing passive overconsumption when consuming energy dense foods is substitution of low energy dense foods. However, palatability differences, access, cost, and habit may prevent people from choosing such foods. Edible mushrooms are very low in calories and energy density. They have a nutrient profile similar to that of many foods recommended in weight loss/maintenance diets. However many " diet" foods have low palatability, which may result in non-adherence to these foods by those seeking to lose weight and keep it off. In contrast, edible mushrooms are generally regarded by adults as highly palatable, making them potentially a good substitute for high energy density foods in the prevention and treatment of obesity. In support of this hypothesis, one study we conducted in humans on the effect of mushroom on satiety and palatability showed promising results, suggesting a potential role in improving weight regulation. In addition, mushrooms may have the added benefit of reducing oxidative stress and inflammation, conditions that are associated with obesity and a number of chronic diseases. Future research is needed on the effect of mushroom intake on body weight regulation, and associated health benefits.

Effects of non-soy legume consumption on C-reactive protein: A systematic review and meta-analysis

Article

May 2015

Because of conflicting results of presented studies, the aim of this systematic review and meta-analysis of randomized clinical trials (RCTs) was to examine the effect of non-soy legume intake on inflammatory markers and C-reactive protein (CRP). We searched Pubmed, ISI Web of Knowledge, SCOPUS, and Google Scholar for relevant studies up to July 2013, using medical subject headings [MeSH] and other related keywords. Nine RCTs were systematically reviewed to examine the effect of non-soy legume consumption on inflammatory markers. Eight studies involving 464 participants were included in the meta-analysis. The results of the meta-analysis showed that non-soy legume consumption had a trend toward a significant effect on decreasing CRP and high-sensitivity (hs)-CRP concentrations (mean difference (MD) = -0.21; 95% confidence interval [CI], -0.44 to 0.02; P = 0.068). There was no overall effect of non-soy legume consumption on CRP or hs-CRP levels in either the parallel or crossover study designs. Our subgroup analysis of CRP type and study design, showed that non-soy legume intake had a significant effect on CRP levels in parallel studies (MD = -1.01; 95% CI, -1.78 to -0.23; P = 0.011) and a significant effect on hs-CRP levels (MD = -0.53; 95% CI, -0.95 to -0.11; P = 0.014) and in the crossover sub group (MD = -0.68; 95% CI, -1.28 to -0.08; P = 0.026). This review of RCTs showed that non-soy legume consumption may contribute to reductions in CRP and hs-CRP concentrations. However, further controlled clinical trials are needed to investigate the effect of non-soy legume intake on other inflammatory markers. Copyright © 2015 Elsevier Inc. All rights reserved.

Effective Diet and Exercise Interventions to Improve Body Composition in Obese Individuals

Article

Jan 2013

Janet Walberg Rankin

Because higher body fat and lower lean mass is associated with excess morbidity and mortality, health care teams need specific science-based recommendations to advise clients on lifestyle approaches to alter body composition. Combining exercise with modest energy restriction is recommended to cause up to 20% more weight and fat loss, improved function, and reduced lean mass loss than modification of diet alone. The optimal diet for developing a leaner body composition is one that is modestly reduced in energy and contains lower fat and higher protein than average. Aerobic exercise alone may cause minimal change in body weight (1%-3%) and fat if greater than 250 min/wk. Higher intensity or duration of exercise can cause more substantial fat loss but may have poor long-term compliance. Resistance exercise boosts lean body mass and improves some health indicators but generally does not cause fat loss. In summary, consumption of a low-fat (20%-25% of energy), moderately high-protein (>1.2 g/kg and up to 20%-25% of energy) diet with modestly reduced energy (500-1000 kcal/d) combined with aerobic (3-5 d/wk, at least 250 min/wk) and resistance exercise (2 d/wk) can improve body composition to reduce clinically relevant risks associated with obesity.

Dietary Composition During Weight-Loss Maintenance—Reply

Article

Sep 2012

In Reply: Dr Weaver correctly observes that the trend test with equal spacing among diets from lowest to highest glycemic load (low-fat, low–glycemic index, and very low-carbohydrate diet) amounts to a pairwise comparison of the low-fat and very low-carbohydrate diets. We obtained an identical result, which was not reported, when the diets were spaced according to calculated glycemic load (185.1, 51.1, and 3.9 g/2000 kcal/d, respectively; P = .05). In any event, we subjected all outcomes to a 3-group analysis of variance and to a test for linear trend. We agree that the former is more stringent than the latter, and that interpretation of the CRP result requires caution. Some1,2 but not all3 studies of this topic have similarly reported higher CRP levels for a low-carbohydrate vs low-fat diet, and this issue warrants additional study.

Long-Term Effects of 4 Popular Diets on Weight Loss and Cardiovascular Risk Factors: A Systematic Review of Randomized Controlled Trials

Article

Nov 2014

Background: We conducted a systematic review to examine the efficacy of the Atkins, South Beach, Weight Watchers (WW), and Zone diets, with a particular focus on sustained weight loss at ≥12 months. Methods and results: We systematically searched MEDLINE, EMBASE, and the Cochrane Library of Clinical Trials to identify randomized controlled trials (RCTs) published in English with follow-up ≥4 weeks that examined the effects of these 4 popular diets on weight loss and cardiovascular risk factors. We identified 12 RCTs (n=2559) with follow-up ≥12 months: 10 versus usual care (5 Atkins, 4 WW, and 1 South Beach) and 2 head-to-head (1 of Atkins, WW, and Zone, and 1 of Atkins, Zone, and control). At 12 months, the 10 RCTs comparing popular diets to usual care revealed that only WW was consistently more efficacious at reducing weight (range of mean changes: -3.5 to -6.0 kg versus -0.8 to -5.4 kg; P<0.05 for 3/4 RCTs). However, the 2 head-to-head RCTs suggest that Atkins (range: -2.1 to -4.7 kg), WW (-3.0 kg), Zone (-1.6 to -3.2 kg), and control (-2.2 kg) all achieved modest long-term weight loss. Twenty-four-month data suggest that weight lost with Atkins or WW is partially regained over time. Conclusions: Head-to-head RCTs, providing the most robust evidence available, demonstrated that Atkins, WW, and Zone achieved modest and similar long-term weight loss. Despite millions of dollars spent on popular commercial diets, data are conflicting and insufficient to identify one popular diet as being more beneficial than the others.

EFFECTS OF AGING OR DIET ON OXIDATIVE MODIFICATION AND ANTIOXIDANT ENZYMES

Article

Positive effect of mushrooms substituted for meat on body weight, body composition, and health parameters. A 1-year randomized clinical trial

Article

Sep 2013
APPETITE

High-fat meal induced postprandial inflammation

Article

Jan 2014
MOL NUTR FOOD RES

Raised levels of circulating inflammatory markers are associated with coronary artery disease, obesity and type II diabetes. It has been proposed that the ingestion of high-fat meals may serve as a stimulus to raise systemic inflammatory tone, although interventional studies have yielded conflicting results. We here review 57 studies of high-fat meal induced acute postprandial inflammation to identify the most frequently reported markers of postprandial inflammation and to compare these results with the highly consistent low-grade endotoxaemia model in man. Most plasma borne markers of inflammation, such as cytokines and soluble adhesion molecules, were not consistently raised after a high-fat meal. However, pro-inflammatory leukocyte surface markers, mRNA and proteins were elevated in almost all studies in which they were measured. These markers followed kinetics similar to those observed following intravenous injection of low doses of endotoxin in man, were positively associated with likelihood of contamination of test meals with pro-inflammatory bacterial molecules and were reduced in several studies examining parallel meals supplemented with foodstuffs containing anti-inflammatory phytochemicals. Future studies of postprandial inflammation may yield more consistent evidence by focusing on leukocyte, rather than plasma-borne, markers of inflammation and by considering the test meal content of pro- and anti-inflammatory dietary constituents.

Obesity and Colorectal Cancer

Article

Full-text available

Jan 2012

Obesity worldwide is constantly increasing. Obesity acts as an independent significant risk factor for malignant tumors of various organs including colorectal cancer. Visceral adipose tissue is physiologically more important than subcutaneous adipose tissue. The relative risk of colorectal cancer of obese patients is about 1.5 times higher than the normal-weight individuals, and obesity is also associated with premalignant colorectal adenoma. The colorectal cancer incidence of obese patients has gender-specific and site-specific characteristics that it is higher in men than women and in the colon than rectum. Obesity acts as a risk factor of colorectal carcinogenesis by several mechanisms. Isulin, insulin-like growth factor, leptin, adiponectin, microbiome, and cytokines of chronic inflammation etc. have been understood as its potential mechanisms. In addition, obesity in patients with colorectal cancer negatively affects the disease progression and response of chemotherapy. Although the evidence is not clear yet, there are some reports that weight loss as well as life-modification such as dietary change and physical activity can reduce the risk of colorectal cancer. It is very important knowledge in the point that obesity is a potentially modifiable risk factor that can alter the incidence and outcome of the colorectal cancer.

Differential effects of low-carbohydrate and low-fat diets on inflammation and endothelial function in diabetes

Article

Nov 2011

To characterize acute (postprandial) and chronic (after a 6-month period of weight loss) effects of a low-carbohydrate vs. a low-fat diet on subclinical markers of cardiovascular disease (CVD) in adults with type 2 diabetes. At baseline and 6 months, measures of C-reactive protein (CRP), interleukin-6 (IL-6), soluble intercellular adhesion molecule (sICAM) and soluble E-selectin were obtained from archived samples (n = 51) of participants randomized in a clinical trial comparing a low-carbohydrate and a low-fat diet. In a subset of participants (n = 27), postprandial measures of these markers were obtained 3 h after a low-carbohydrate or low-fat liquid meal. Endothelial function was also measured by reactive hyperemic peripheral arterial tonometry during the meal test. Paired t tests and unpaired t tests compared within- and between-group changes. There were no significant differences observed in postprandial measures of inflammation or endothelial function. After 6 months, CRP (mean ± S.E.) decreased in the low-fat arm from 4.0 ± 0.77 to 3.0 ± 0.77 (P = .01). In the low-carbohydrate arm, sICAM decreased from 234 ± 22 to 199 ± 23 (P = .001), and soluble E-selectin decreased from 93 ± 10 to 82 ± 10 (P = .05.) A significant correlation between change in high-density lipoprotein and change in soluble E-selectin (r = -0.33, P = .04) and with the change in ICAM (r = -0.43, P = .01) was observed. Low-carbohydrate and low-fat diets both have beneficial effects on CVD markers. There may be different mechanisms through which weight loss with these diets potentially reduces CVD risk.

Does intentional weight loss reduce cancer risk?

Article

Jul 2011
DIABETES OBES METAB

Epidemiologic evidence points to obesity as a major risk factor for many cancers, including cancers of the breast, endometrium, colorectum, kidney, oesophagus and pancreas. Whether intentional weight loss might reduce this excess risk is not yet proven. We searched the medical literature for studies reporting changes in cancer risk following intentional weight loss, and for studies reporting changes in cancer-relevant risk factors of oestrogens, sex hormone binding globulin (SHBG), Insulin-like growth factor-I (IGF-I), IGF binding proteins and selected inflammatory markers [C-reactive protein (CRP), interleukin 6 (IL-6) and tumour necrosis factor-α (TNF-α)]. Observational cohort studies and randomized controlled trials of both dietary interventions and bariatric surgery all indicate fairly immediate reductions in cancer incidence following intentional weight loss. Oestrogen levels drop and SHBG levels increase coincident with intentional weight loss, with about a one-third reduction in free oestradiol to be expected from a 10% weight loss. CRP levels also drop substantially after weight loss at about this same 3 : 1 ratio. Reductions in TNF-α and IL-6 are consistently seen, but of a smaller magnitude, and IGF-I and IGFBP changes after weight loss are small and inconsistent. Because both cancer incidence and levels of circulating cancer biomarkers drop fairly rapidly following weight loss, intentional weight loss may well lead to meaningful reductions in cancer risk with a short latency time.

Dietary Fat and Carbohydrate Composition: Metabolic Disease

Chapter

Sep 2010

The term “metabolic syndrome” is used to describe a cluster of disease states including blood lipid disorders, hypertension, propensity for thrombus formation, low-grade chronic inflammation, abdominal obesity, and type-2 diabetes. Insulin resistance is the key to the metabolic syndrome, particularly the relative failure of insulin to exert its multiple biological effects on carbohydrate and lipid metabolism. The current epidemic of obesity and type-2 diabetes in developed and developing countries has focused major attention on the metabolic derangements critical to their etiology. The Banting lecture of 20 years ago by Reaven sparked great interest in the clustering of diseases, which he termed “Syndrome X” and subsequently is more commonly referred to as the metabolic syndrome (Reaven, 1988). The basic symptomatology included dyslipidemias (high cholesterol and triglycerides), insulin resistance, obesity, and hypertension. With continuing research, subsequent iterations have added central (and in particular visceral) adiposity and chronic low-grade inflammation as key elements. Diet plays a powerful role in modulating expression of the metabolic syndrome and it is increasingly clear that both amount and type of both fats and carbohydrates, and the interaction between them, are important variables.

Excess body weight and obesity—The link with gastrointestinal and hepatobiliary cancer

Article

Mar 2011
NAT REV GASTRO HEPAT

Excess body weight (EBW) is an independent risk factor for many human malignancies, including cancers throughout the gastrointestinal and hepatobiliary tract from the esophagus to the colorectum. The relative risk of gastrointestinal cancer in obese individuals is approximately 1.5-2.0 times that for normal weight individuals, with organ-specific and gender-specific differences for specific cancers. The association between EBW and risk of premalignant stages of gastrointestinal carcinogenesis, such as colorectal adenoma and Barrett esophagus, is similar, implying a role for EBW during the early stages of carcinogenesis that could be relevant to preventative strategies. EBW also impacts negatively on gastrointestinal cancer outcomes. The mechanistic basis of the association between EBW and carcinogenesis remains incompletely understood. Postulated mechanisms include increased insulin and insulin-like growth factor signaling and chronic inflammation (both linked to the metabolic syndrome), as well as signaling via adipokines, such as leptin. The role of obesity-related changes in the intestinal microbiome in gastrointestinal carcinogenesis deserves further attention. Whether weight loss leads to reduced future gastrointestinal and liver cancer risk has yet to be fully explored. There is some support for the idea that weight loss negatively regulates colorectal carcinogenesis. In addition, data suggest a reduction in risk of several cancers in the first 10 years after bariatric surgery.

Elevated C-Reactive Protein Levels in Overweight and Obese Adults

Article

Full-text available

Dec 1999

Human adipose tissue expresses and releases the proinflammatory cytokine interleukin 6, potentially inducing low-grade systemic inflammation in persons with excess body fat. To test whether overweight and obesity are associated with low-grade systemic inflammation as measured by serum C-reactive protein (CRP) level. The Third National Health and Nutrition Examination Survey, representative of the US population from 1988 to 1994. A total of 16616 men and nonpregnant women aged 17 years or older. Elevated CRP level of 0.22 mg/dL or more and a more stringent clinically raised CRP level of more than 1.00 mg/dL. Elevated CRP levels and clinically raised CRP levels were present in 27.6% and 6.7% of the population, respectively. Both overweight (body mass index [BMI], 25-29.9 kg/m2) and obese (BMI, > or =30 kg/m2) persons were more likely to have elevated CRP levels than their normal-weight counterparts (BMI, <25 kg/m2). After adjustment for potential confounders, including smoking and health status, the odds ratio (OR) for elevated CRP was 2.13 (95% confidence interval [CI], 1.56-2.91) for obese men and 6.21 (95% CI, 4.94-7.81) for obese women. In addition, BMI was associated with clinically raised CRP levels in women, with an OR of 4.76 (95% CI, 3.42-6.61) for obese women. Waist-to-hip ratio was positively associated with both elevated and clinically raised CRP levels, independent of BMI. Restricting the analyses to young adults (aged 17-39 years) and excluding smokers, persons with inflammatory disease, cardiovascular disease, or diabetes mellitus and estrogen users did not change the main findings. Higher BMI is associated with higher CRP concentrations, even among young adults aged 17 to 39 years. These findings suggest a state of low-grade systemic inflammation in overweight and obese persons.

Markers of chronic inflammation and obesity: A prospective study on the reversibility of this association in middle-aged women undergoing weight loss by surgical intervention

Article

Full-text available

Jun 2002

Human adipose tissue expresses and releases proinflammatory cytokines and these measures of chronic inflammation have recently been associated with obesity. To test whether the proinflammatory state is reversible in subjects undergoing weight loss by surgical measures. Twenty morbidly obese women participated in this prospective study. Subjects were examined for fat mass, high-sensitive C-reactive protein (hs-CRP), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) before and 1 y after Swedish adjustable gastric banding. Anthropometric measures displayed a significant reduction of the body mass index (BMI) from 41.6+/-5.4 to 30.8+/-6.1 kg/m(2) and the fat mass from 53.9+/-10.3 to 29.8+/-12.1 kg (mean+/-s.d.). Hs-CRP levels decreased significantly from 1.33+/-1.21 mg/dl in pre-gastric banding subjects to 0.40+/-0.61 mg/dl in post-gastric banding subjects, respectively. IL-6 and TNF-alpha levels did not differ significantly between pre- and post-gastric banding subjects. We speculate that in these patients the marked reduction in C-reactive protein might be beneficial in reducing their cardiovascular risk and is not solely mediated by IL-6 and TNF-alpha.

A Randomized Trial of a Low-Carbohydrate Diet for Obesity

Article

Full-text available

Jun 2003
NEW ENGL J MED

Despite the popularity of the low-carbohydrate, high-protein, high-fat (Atkins) diet, no randomized, controlled trials have evaluated its efficacy. We conducted a one-year, multicenter, controlled trial involving 63 obese men and women who were randomly assigned to either a low-carbohydrate, high-protein, high-fat diet or a low-calorie, high-carbohydrate, low-fat (conventional) diet. Professional contact was minimal to replicate the approach used by most dieters. Subjects on the low-carbohydrate diet had lost more weight than subjects on the conventional diet at 3 months (mean [+/-SD], -6.8+/-5.0 vs. -2.7+/-3.7 percent of body weight; P=0.001) and 6 months (-7.0+/-6.5 vs. -3.2+/-5.6 percent of body weight, P=0.02), but the difference at 12 months was not significant (-4.4+/-6.7 vs. -2.5+/-6.3 percent of body weight, P=0.26). After three months, no significant differences were found between the groups in total or low-density lipoprotein cholesterol concentrations. The increase in high-density lipoprotein cholesterol concentrations and the decrease in triglyceride concentrations were greater among subjects on the low-carbohydrate diet than among those on the conventional diet throughout most of the study. Both diets significantly decreased diastolic blood pressure and the insulin response to an oral glucose load. The low-carbohydrate diet produced a greater weight loss (absolute difference, approximately 4 percent) than did the conventional diet for the first six months, but the differences were not significant at one year. The low-carbohydrate diet was associated with a greater improvement in some risk factors for coronary heart disease. Adherence was poor and attrition was high in both groups. Longer and larger studies are required to determine the long-term safety and efficacy of low-carbohydrate, high-protein, high-fat diets.

The 6-a-day study: Effects of fruit and vegetables on markers of oxidative stress and antioxidative defense in healthy nonsmokers

Article

Full-text available

Jul 2004

Fruit and vegetables contain both nutritive and nonnutritive factors that might contribute to redox (antioxidant and prooxidant) actions. We investigated the relative influence of nutritive and nonnutritive factors in fruit and vegetables on oxidative damage and enzymatic defense. A 25-d intervention study with complete control of dietary intake was performed in 43 healthy male and female nonsmokers who were randomly assigned to 1 of 3 groups. In addition to a basic diet devoid of fruit and vegetables, the fruit and vegetables (Fruveg) group received 600 g fruit and vegetables/d; the placebo group received a placebo pill, and the supplement group received a vitamin pill designed to contain vitamins and minerals corresponding to those in 600 g fruit and vegetables. Biomarkers of oxidative damage to protein and lipids and of antioxidant nutrients and defense enzymes were determined before and during intervention. Plasma lipid oxidation lag times increased during intervention in the Fruveg and supplement groups, and the increase was significantly higher in the former. Plasma protein carbonyl formation at lysine residues also increased in both of these groups. Glutathione peroxidase activity increased in the Fruveg group only. Other markers of oxidative damage, oxidative capacity, or antioxidant defense were largely unaffected by the intervention. Fruit and vegetables increase erythrocyte glutathione peroxidase activity and resistance of plasma lipoproteins to oxidation more efficiently than do the vitamins and minerals that fruit and vegetables are known to contain. Plasma protein carbonyl formation at lysine residues increases because of the vitamins and minerals in fruit and vegetables.

Overweight and Obesity Among U. S. Children, Adolescents, and Adults, 1999-2002

Article

Full-text available

Jun 2004
J Am Med Assoc

The prevalence of overweight and obesity has increased markedly in the last 2 decades in the United States. To update the US prevalence estimates of overweight in children and obesity in adults, using the most recent national data of height and weight measurements. As part of the National Health and Nutrition Examination Survey (NHANES), a complex multistage probability sample of the US noninstitutionalized civilian population, both height and weight measurements were obtained from 4115 adults and 4018 children in 1999-2000 and from 4390 adults and 4258 children in 2001-2002. Prevalence of overweight (body mass index [BMI] > or =95th percentile of the sex-specific BMI-for-age growth chart) among children and prevalence of overweight (BMI, 25.0-29.9), obesity (BMI > or =30.0), and extreme obesity (BMI > or =40.0) among adults by sex, age, and racial/ethnic group. Between 1999-2000 and 2001-2002, there were no significant changes among adults in the prevalence of overweight or obesity (64.5% vs 65.7%), obesity (30.5% vs 30.6%), or extreme obesity (4.7% vs 5.1%), or among children aged 6 through 19 years in the prevalence of at risk for overweight or overweight (29.9% vs 31.5%) or overweight (15.0% vs 16.5%). Overall, among adults aged at least 20 years in 1999-2002, 65.1% were overweight or obese, 30.4% were obese, and 4.9% were extremely obese. Among children aged 6 through 19 years in 1999-2002, 31.0% were at risk for overweight or overweight and 16.0% were overweight. The NHANES results indicate continuing disparities by sex and between racial/ethnic groups in the prevalence of overweight and obesity. There is no indication that the prevalence of obesity among adults and overweight among children is decreasing. The high levels of overweight among children and obesity among adults remain a major public health concern.

Established and Emerging Plasma Biomarkers in the Prediction of First Atherothrombotic Events

Article

Full-text available

Jul 2004
CIRCULATION

There is considerable pathophysiologic and clinical interest in the development of novel biomarkers for inflammation, hemostasis, thrombosis, and oxidative stress that may help in the detection of individuals at high risk for future vascular events. However, as outlined in Table 1, few of these markers have demonstrated an ability to predict risk over and above information available from global assessment tools such as the Framingham Risk Score, and no evidence is available demonstrating that specific reductions in any of these novel markers will lower vascular risk. Although this overview has focused on the role of biomarkers for prognosis in primary prevention, it remains possible that several biomarkers will prove useful for demonstrating efficacy of therapy or in predicting specific patient groups more or less likely to benefit from targeted interventions. It also remains probable that no single biomarker will emerge that provides appropriate information for all clinical settings; thus, multimarker approaches also need evaluation. Ongoing efforts in plasma-based biomarker research will simultaneously need to address novel pathways of disease and carefully evaluate clinical applications and clinical efficacy.

Weight loss leads to reductions in inflammatory biomarkers after a very-low-carbohydrate diet and a low-fat diet in overweight men

Article

Full-text available

Nov 2004

In recent years, it has become apparent that low-grade vascular inflammation plays a key role in all stages of the pathogenesis of atherosclerosis. Weight loss has been shown to improve blood inflammatory markers; however, it is unknown if weight-loss diets varying in macronutrient composition differentially affect inflammatory responses. The primary purpose of the present study was to compare a very-low-carbohydrate diet and a low-fat weight-loss diet on inflammatory biomarkers in overweight men. In a randomized cross-over design, 15 overweight men (body fat, >25%; body mass index, 34 kg/m2) consumed two experimental weight-loss diets for two consecutive 6-week periods: a very-low-carbohydrate diet (<10% energy via carbohydrate) and a low-fat diet (<30% energy via fat). Both the low-fat and the very-low-carbohydrate diets resulted in significant decreases in absolute concentrations of hsTNF-alpha (high-sensitivity tumour necrosis factor-alpha), hsIL-6 (high-sensitivity interleukin-6), hsCRP (high-sensitivity C-reactive protein) and sICAM-1 (soluble intercellular cell-adhesion molecule-1). There was no significant change in absolute sP-selectin (soluble P-selectin) concentrations after either diet. Normalized inflammatory values represented as the delta change per 1 kg reduction in body mass showed a significant difference between the two diets only for sP-selectin (P<0.05). In summary, energy-restricted low-fat and very-low-carbohydrate diets both significantly decreased several biomarkers of inflammation. These data suggest that, in the short-term, weight loss is primarily the driving force underlying the reductions in most of the inflammatory biomarkers.

Effective treatments for insulin resistance: Trim the fat and douse the fire

Article

Full-text available

Dec 2004
TRENDS ENDOCRIN MET

Currently, only limited treatments are available for insulin resistance, a major cause of type 2 diabetes (T2D) and the metabolic syndrome. Combined innovative pharmaceutical and non-pharmaceutical strategies are needed. Obesity, a major cause of insulin resistance in T2D, can be treated relatively safely with modern bariatric surgery. Exercise training to increase VO(2max) is an important non-pharmaceutical approach to decrease insulin resistance. The thiazolidinediones are useful in treating insulin resistance, but newer agents with broader specificity might be more efficacious without deleterious side effects. Recently oxidative stress has been implicated in insulin resistance. One antioxidant that is safe and appears effective is alpha-lipoic acid. Thus, combinations of surgery, exercise training, insulin sensitizers and antioxidants will probably constitute future insulin resistance management.

Major dietary patterns are related to plasma concentrations of markers of inflammation and endothelial dysfunction

Article

Oct 2004

Background: Endothelial dysfunction is one of the mechanisms linking diet and the risk of cardiovascular disease. Objective: We evaluated the hypothesis that dietary patterns (summary measures of food consumption) are directly associated with markers of inflammation and endothelial dysfunction, particularly C-reactive protein (CRP), interleukin 6, E-selectin, soluble intercellular adhesion molecule 1 (sICAM-1), and soluble vascular cell adhesion molecule 1 (sVCAM-1). Design: We conducted a cross-sectional study of 732 women from the Nurses' Health Study I cohort who were 43-69 y of age and free of cardiovascular disease, cancer, and diabetes mellitus at the time of blood drawing in 1990. Dietary intake was documented by using a validated food-frequency questionnaire in 1986 and 1990. Dietary patterns were generated by using factor analysis. Results: A prudent pattern was characterized by higher intakes of fruit, vegetables, legumes, fish, poultry, and whole grains, and a Western pattern was characterized by higher intakes of red and processed meats, sweets, desserts, French fries, and refined grains. The prudent pattern was inversely associated with plasma concentrations of CRP (P = 0.02) and E-selectin (P = 0.001) after adjustment for age, body mass index (BMI), physical activity, smoking status, and alcohol consumption. The Western pattern showed a positive relation with CRP (P < 0.001), interleukin 6 (P = 0.006), E-selectin (P < 0.001), sICAM-1 (P < 0.001), and sVCAM-1 (P = 0.008) after adjustment for all confounders except BMI; with further adjustment for BMI, the coefficients remained significant for CRP (P = 0.02), E-selectin (P < 0.001), sICAM-1 (P = 0.002), and sVCAM-1 (P = 0.02). Conclusion: Because endothelial dysfunction is an early step in the development of atherosclerosis, this study suggests a mechanism for the role of dietary patterns in the pathogenesis of cardiovascular disease.

Benedict FG: A Biometric Study of Basal Metabolism in Man. Washington, DC

Article

J.A. Harris

A Low-Carbohydrate, Ketogenic Diet versus a Low-Fat Diet To Treat Obesity and Hyperlipidemia

Article

May 2004

William S Yancy

A randomized study comparing the effects of a low-carbohydrate diet and a conventional diet on lipoprotein subfractions and C-reactive protein levels in patients with severe obesity

Article

Jan 2005

C-Reactive Protein, the Metabolic Syndrome, and Prediction of Cardiovascular Events in the Framingham Offspring Study

Article

Nov 2004

Background-Inflammation (assessed by C-reactive protein [CRP]) and the metabolic syndrome (MetS) are associated with cardiovascular disease (CVD), but population-based data are limited. Methods and Results-We assessed the cross-sectional relations of CRP to the MetS ( National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, Adult Treatment Panel III definition) in 3037 subjects ( 1681 women; mean age, 54 years) and the utility of CRP and the MetS to predict new CVD events (n = 189) over 7 years. MetS (greater than or equal to3 of 5 traits) was present in 24% of subjects; mean age-adjusted CRP levels for those with 0, 1, 2, 3, 4, or 5 MetS traits were 2.2, 3.5, 4.2, 6.0, or 6.6 mg/L, respectively (P trend < 0.0001). In persons with MetS, age-adjusted CRP levels were higher in women than men (7.8 versus 4.6 mg/L; P < 0.0001). MetS and baseline CRP were individually related to CVD events (for MetS: age-sex-adjusted hazard ratio [HR], 2.1; 95% CI, 1.5 to 2.8; for highest versus lowest CRP quartile: HR, 2.2; 95% CI, 1.4 to 3.5). Greater risk of CVD persisted for MetS and CRP even after adjustment in a model including age, sex, MetS (HR, 1.8; 95% CI, 1.4 to 2.5), and CRP (HR, 1.9; 95% CI, 1.2 to 2.9). The c-statistic associated with the age- and sex-adjusted model including CRP was 0.72; including MetS, 0.74; and including CRP and MetS, 0.74. Conclusions-Elevated CRP levels are related to insulin resistance and the presence of the MetS, especially in women. Although discrimination of subjects at risk of CVD events using both MetS and CRP is not better than using either phenotype alone, both CRP and MetS are independent predictors of new CVD events.

A Low-Carbohydrate, Ketogenic Diet versus a Low-Fat Diet to Treat Obesity and Hyperlipidemia: A Randomized, Controlled Trial

Article

Aug 2004

Background: Low-carbohydrate diets remain popular despite a paucity of scientific evidence on their effectiveness. Objective: To compare the effects of a low-carbohydrate, ketogenic diet program with those of a low-fat, low-cholesterol, reduced-calorie diet. Design: Randomized, controlled trial. Setting: Outpatient research clinic. Participants: 120 overweight, hyperlipidemic volunteers from the community. Intervention: Low-carbohydrate diet (initially, <20 g of carbohydrate daily) plus nutritional supplementation, exercise recommendation, and group meetings, or low-fat diet (<30% energy from fat, <300 mg of cholesterol daily, and deficit of 500 to 1000 kcal/d) plus exercise recommendation and group meetings. Measurements: Body weight, body composition, fasting serum lipid levels, and tolerability. Results: A greater proportion of the low-carbohydrate diet group than the low-fat diet group completed the study (76% vs. 57%; P = 0.02). At 24 weeks, weight loss was greater in the low-carbohydrate diet group than in the low-fat diet group (mean change, -12.9% vs. -6.7%; P < 0.001). Patients in both groups lost substantially more fat mass (change, -9.4 kg with the low-carbohydrate diet vs. -4.8 kg with the low-fat diet) than fat-free mass (change, -3.3 kg vs. -2.4 kg, respectively). Compared with recipients of the low-fat diet, recipients of the low-carbohydrate diet had greater decreases in serum triglyceride levels (change, -0.84 mmol/L vs. -0.31 mmol/L [-74.2 mg/dL vs. -27.9 mg/dL]; P = 0.004) and greater increases in high-density lipoprotein cholesterol levels (0.14 mmol/L vs. -0.04 mmol/L [5.5 mg/dL vs. -1.6 mg/dL]; P < 0.001). Changes in low-density lipoprotein cholesterol level did not differ statistically (0.04 mmol/L [1.6 mg/dL] with the low-carbohydrate diet and -0.19 mmol/L [-7.4 mg/dL] with the low-fat diet; P = 0.2). Minor adverse effects were more frequent in the low-carbohydrate diet group. Limitations: We could not definitively distinguish effects of the low-carbohydrate diet and those of the nutritional supplements provided only to that group. In addition, participants were healthy and were followed for only 24 weeks. These factors limit the generalizability of the study results. Conclusions: Compared with a low-fat diet, a low-carbohydrate diet program had better participant retention and greater weight loss. During active weight loss, serum triglyceride levels decreased more and high-density lipoprotein cholesterol level increased more with the low-carbohydrate diet than with the low-fat diet.

Dr. Atkins New Diet Revolution

Book

Jan 2004

RC Atkins

A Diet Rich in Fat and Poor in Dietary Fiber Increases the In Vitro Formation of Reactive Oxygen Species in Human Feces

Article

Jun 1997

Production of reactive oxygen species in the lumen of the colon, a process that is influenced by nutritional factors, may be important in the etiology of colorectal cancer. Because research on humans in support of this hypothesis is lacking, the objective of this study was to measure the effect of different dietary compositions on the in vitro oxygen radical production in human feces. Over a period of 12 d, seven healthy subjects received a diet rich in fat (50%) and meat and poor in dietary fiber. After a period of 1 wk, they received a vegetarian diet poor in fat (20%) and rich in dietary fiber. At the end of each study period, feces were collected and analyzed for in vitro oxygen radical production with dimethylsulfoxide as the free radical scavenger. The mean hydroxyl radical production was 13 times greater in feces of subjects when they consumed the diet rich in fat and poor in dietary fiber [52.7 +/- 29.5 micromol/(g feces x h)] than when they consumed the diet poor in fat and rich in dietary fiber [3.9 +/- 3.9 micromol/(g feces x h); P < 0.05]. This difference was associated with a 42% higher fecal iron concentration when they consumed the first diet (7.0 +/- 19.2 micromol/g feces) than when they consumed the second (4.9 +/- 1.9 micromol/g feces; P < 0.05). The results of this study confirm that diets high in fat and meat and low in fiber markedly increase the potential for hydroxyl radical formation in the feces, which in turn may contribute to an enhanced risk of colorectal cancer.

In vivo total antioxidant capacity: Comparison of different analytical methods

Article

Jan 2000
FREE RADICAL BIO MED

Several methods have been developed to measure the total antioxidant capacity of a biological sample. The use of peroxyl or hydroxyl radicals as pro-oxidants in the oxygen radical absorbance capacity (ORAC) assay makes it different and unique from the assays that involve oxidants that are not necessarily pro-oxidants. An improvement in quantitation is achieved in the ORAC assay by taking the reaction between substrate and free radicals to completion and using an area-under-curve technique for quantitation compared to the assays that measure a lag phase. The interpretation of the changes in plasma or serum antioxidant capacity becomes complicated by the different methods used in detecting these changes. The interpretation also depends upon the conditions under which the antioxidant capacity is determined because the measurement reflects outcomes in a dynamic system. An increased antioxidant capacity in plasma or serum may not necessarily be a desirable condition if it reflects a response to increased oxidative stress. Similarly, a decrease in plasma or serum antioxidant capacity may not necessarily be an undesirable condition if the measurement reflects decreased production of reactive species. Because of these complications, no single measurement of antioxidant status is going to be sufficient, but a "battery" of measurements, many of which will be described in Forum articles, will be necessary to adequately assess oxidative stress in biological systems.

Serum levels of interleukin-6 and dehydroepiandrosterone sulphate in response to either fasting or a ketogenic diet in rheumatoid arthritis patients

Article

May 2000

To investigate the effects of either a 7-day fast or a 7-day ketogenic diet upon serum interleukin-6 (IL-6) and dehydroepiandrosterone sulphate (DHEAS) in RA patients. We measured serum concentrations of DHEAS and IL-6 in 23 RA patients with active disease, 10 of whom followed a 7-day sub-total fast and 13 of whom consumed a ketogenic diet (isoenergetic, carbohydrate < 40 g/day) for 7 days. Clinical and laboratory variables were measured at baseline, on day 7 and after re-feeding on day 21. Correlation analyses were used to assess the associations between serum IL-6, DHEAS and disease activity variables at each timepoint. Fasting, but not the ketogenic diet, decreased serum IL-6 concentrations by 37% (p < 0.03) and improved disease activity at day 7. Both fasting and the ketogenic diet increased serum DHEAS levels by 34% as compared with baseline (both p < 0.006). Levels of IL-6, but not DHEAS, correlated with several disease activity variables. Both fasting and a ketogenic diet significantly increased serum DHEAS concentrations in RA patients. Only fasting significantly decreased serum IL-6 levels and improved disease activity. As the increases in serum DHEAS were similar in response to both fasting and a ketogenic diet, it is unlikely that the fall in serum IL-6 or clinical improvements after fasting were directly related to increases in serum DHEAS. The fasting-induced fall in serum IL-6 may underlie the fall in CRP and ESR observed in RA patients in response to a 7-day fast.

Energy Restriction and Weight Loss on Very-Low-Fat Diets Reduce C-Reactive Protein Concentrations in Obese, Healthy Women

Article

Jun 2001
ARTERIOSCL THROM VAS

C-reactive protein (CRP) is an inflammatory-response protein that is a strong, independent predictor of cardiovascular mortality. CRP is positively associated with body mass index (BMI). In this study, we investigated the effects of dynamic weight loss on CRP in 83 healthy, obese women (mean BMI, 33.8+/-0.4 kg/m(2); range, 28.2 to 43.8 kg/m(2)). Subjects were placed on very-low-fat, energy-restricted diets (5700 kJ, 15% fat) for 12 weeks. Weight, waist and hip circumferences, plasma lipids, glucose, and CRP were measured at baseline and after 12 weeks. CRP was positively associated with BMI (r=0.281, P=0.01) and waist circumference (r=0.278, P=0.01) but was not related to other atherosclerosis risk factors. BMI was significantly different between groups split above or below the median for CRP (34.8+/-0.6 kg/m(2) vs 33.0+/-0.5 kg/m(2), P=0.02). After 12 weeks, weight loss was 7.9+/-0.3 kg. CRP was significantly decreased by 26% (P<0.001), and a correlation was observed between weight loss and the change in CRP (r=0.309, P=0.005). The variance in the change in CRP was partly explained by initial CRP (13.6%), energy intake (5.4%), and percentage weight loss (4.6%, P=0.001). This study confirms recent observations that BMI is associated with CRP, a marker for low-grade systemic inflammation. Furthermore, we observed that CRP was lowered in proportion to weight loss.

Effect of Varying Dietary Fat Levels on Rat Growth and Oxidative DNA Damage

Article

Feb 2001

Dietary fat has previously been shown to have somewhat complicated relationships to levels of oxidative stress in rats. In this study, we examined the effects of five different dietary fat intakes on levels of oxidative DNA damage in rats. Animals fed diets containing 3%, 5%, 10%, or 15% corn oil had body weights that were similar after 20 weeks. Animals fed a 20% fat diet, however, had significantly higher mean body weight than any other group. Levels of 5-hydroxymethyl-2'-deoxyuridine, one marker of oxidative DNA damage, had different relationships to dietary fat in blood and mammary gland. In blood, levels increased with dietary fat levels, and the highest levels were observed with the 20% fat diet (65% higher levels than with the 3% fat diet). In mammary gland, a plateau-type effect was observed, with maximal levels of oxidative DNA damage being obtained using 10% fat (representing a 68% increase relative to the 3% fat diet). This could be a result of induction of compensatory mechanisms in response to a high-fat diet in mammary gland but not in the short-lived nucleated blood cells. Oxidative DNA damage levels in blood thus appear to be a marker of dietary fat intake. In mammary gland, however, levels of DNA damage are consistent with previously observed promotional effects of dietary fat on mammary gland tumorigenesis at lower levels of fat intake with little or no incremental promoting effects at higher levels of fat intake.

Weight Loss Reduces C-Reactive Protein Levels in Obese Postmenopausal Women

Article

Feb 2002
CIRCULATION

C-reactive protein (CRP) has been proposed as an independent risk factor for cardiovascular disease and has been positively associated with body weight and body fatness. We examined the hypothesis that weight loss would reduce plasma CRP levels in obese postmenopausal women. In a sample of 61 obese (body mass index, 35.6 +/- 5.0 kg/m(2)), postmenopausal women (age, 56.4 +/- 5.2 years), we found that plasma CRP levels were positively associated with dual x-ray absorptiometry-measured total body fatness (r=0.36, P<0.005) and CT-measured intra-abdominal body fat area (r=0.30, P<0.02). Significant correlations were also found between plasma CRP and triglyceride levels (r=0.33, P<0.009) and glucose disposal measured by the hyperinsulinemic-euglycemic clamp technique (r=-0.29, P<0.03). Twenty-five of the 61 women tested at baseline completed a weight loss protocol. The average weight loss was 14.5 +/- 6.2 kg (-15.6%, P<0.0001), with losses of 10.4 +/- 5.4 kg fat mass (-25.0%, P<0.0001) and 2.8 +/- 1.4 kg fat-free mass (-6.0%, P<0.0001). Visceral and subcutaneous fat areas were reduced by -36.4% and -23.7%, respectively (P<0.0001). Plasma CRP levels were significantly reduced by weight loss: average -32.3%, from 3.06 (+0.69, -1.29) to 1.63 (+0.70, -0.75) microgram/mL (P<0.0001, medians and interquartile differences). Changes in body weight and in total body fat mass were both positively associated with plasma CRP level reductions. Adiposity was a significant predictor of plasma CRP in postmenopausal women on a cross-sectional basis. Moreover, caloric restriction-induced weight loss decreased plasma CRP levels. Weight loss may represent an important intervention to reduce CRP levels, which may mediate part of its cardioprotective effects in obese postmenopausal women.

Relation between a diet with a high glycemic load and plasma concentrations of high-sensitivity C-reactive protein in middle-aged women 1-3

Article

Mar 2002

Recent prospective data suggest that intake of rapidly digested and absorbed carbohydrates with a high dietary glycemic load is associated with an increased risk of ischemic heart disease. We examined whether a high dietary glycemic load was associated with elevated hs-CRP concentrations and whether this association was modified by body mass index (BMI; in kg/m(2)). In 244 apparently healthy women, we measured plasma hs-CRP concentrations and determined average dietary glycemic loads with a validated semiquantitative food-frequency questionnaire. Using multiple regression models, we evaluated the association between dietary glycemic load and plasma hs-CRP after adjusting for age; treatment status; smoking status; BMI; physical activity level; parental history of myocardial infarction; history of hypertension, diabetes, and high cholesterol; postmenopausal hormone use; alcohol intake; and other dietary variables. We found a strong and statistically significant positive association between dietary glycemic load and plasma hs-CRP. The median hs-CRP concentration for the lowest quintile of dietary glycemic load was 1.9 mg/L and for the highest quintile was 3.7 mg/L; corresponding multivariate-adjusted geometric means were 1.4 and 3.8 mg/L, respectively (P for trend < 0.01). This association was significantly modified by BMI. Among women with a BMI greater-than-or-equal 25, the multivariate-adjusted geometric mean hs-CRP concentration in the lowest quintile was 1.6 mg/L and in the highest quintile was 5.0 mg/L; however, among women with a BMI < 25, the corresponding means were 1.1 and 3.1 mg/L, respectively (P = 0.01 for interaction). Dietary glycemic load is significantly and positively associated with plasma hs-CRP in healthy middle-aged women, independent of conventional risk factors for ischemic heart disease. Exacerbation of the proinflammatory process may be a mechanism whereby a high intake of rapidly digested and absorbed carbohydrates increases the risk of ischemic heart disease, especially in overweight women prone to insulin resistance.

C-reactive protein and coronary artery disease: Influence of obesity, caloric restriction and weight loss

Article

Jul 2002

C reactive protein (CRP) values in blood are a good indicator of the likelihood of acute coronary and cerebral events in both healthy subjects and patients with coronary artery disease. This indicates that atherosclerotic lesions rich in inflammatory cells and cytokines are more likely to produce acute events either through vasospasm and/or thrombosis and also can be readily detected through elevations in CRP when measured using a high sensitivity assay (hsCRP). However the arterial wall is only one potential source of cytokines which induce CRP production. Fat cells also produce cytokines, in particular IL-6 which induces the synthesis of CRP by the liver. Obesity, especially abdominal obesity, is associated with elevations of hsCRP. This may be of pathogenic significance as CRP stimulates the uptake of LDL by macrophages, induces complement activation which may cause cellular damage in the artery, and enhances monocyte production of tissue factor, thus enhancing the risk of thrombosis. Caloric restriction and weight loss lowers IL-6 and CRP levels and may beneficially suppress an immune response. Whether particular dietary macronutrients or micronutrients alter IL-6 or CRP is unknown but this issue is clearly becoming more important.

Lipid Lowering Reduces Oxidative Stress and Endothelial Cell Activation in Rabbit Atheroma

Article

Oct 2002
CIRCULATION

Lipid lowering may reduce acute coronary events in patients in part by reducing vascular inflammation. Oxidative stress induces endothelial cell (EC) expression of vascular cell adhesion molecule 1 (VCAM-1) and monocyte chemoattractant protein 1 (MCP-1) and reduces levels of atheroprotective NO, leading to monocyte recruitment and macrophage accumulation. This study tested the hypothesis that lipid lowering decreases oxidative stress and improves EC functions related to inflammatory cell accumulation. Rabbits consumed an atherogenic diet for 4 months to produce atheroma, followed by a purified chow diet for 16 months. Atherosclerotic aortas from hypercholesterolemic rabbits produced high levels of reactive oxygen species. Oxidized LDL (oxLDL) accumulated in atheroma underlying ECs that overexpress VCAM-1. In contrast, few if any ECs in atheroma stained for endothelial NO synthase (eNOS). Lipid lowering reduced reactive oxygen species production, oxLDL accumulation, and plasma levels of anti-oxLDL IgG. After lipid lowering, VCAM-1 and MCP-1 expression decreased, eNOS expression increased, and ECs exhibited a more normal ultrastructure. These results establish that lipid lowering can reduce oxidative stress and EC activation in vivo. These mechanisms may contribute to improvement in endothelial function and plaque stabilization observed clinically.

Obesity and Systemic Oxidative Stress: Clinical Correlates of Oxidative Stress in The Framingham Study

Article

Apr 2003
ARTERIOSCL THROM VAS

To determine the clinical conditions associated with systemic oxidative stress in a community-based cohort. Information regarding cardiovascular risk factors associated with systemic oxidative stress has largely been derived from highly selected samples with advanced stages of vascular disease. Thus, it has been difficult to evaluate the relative contribution of each cardiovascular risk factor to systemic oxidative stress and to determine whether such risk factors act independently and are applicable to the general population. We examined 2828 subjects from the Framingham Heart Study and measured urinary creatinine-indexed levels of 8-epi-PGF2alpha as a marker of systemic oxidative stress. Age- and sex-adjusted multivariable regression models were used to assess clinical correlates of oxidative stress. In age- and sex-adjusted models, increased urinary creatinine-indexed 8-epi-PGF2alpha levels were positively associated with female sex, hypertension treatment, smoking, diabetes, blood glucose, body mass index, and a history of cardiovascular disease. In contrast, age and total cholesterol were negatively correlated with urinary creatinine-indexed 8-epi-PGF2alpha levels. After adjustment for several covariates, decreasing age and total/HDL cholesterol ratio, sex, smoking, body mass index, blood glucose, and cardiovascular disease remained associated with urinary 8-epi-PGF2alpha levels. Smoking, diabetes, and body mass index were highly associated with systemic oxidative stress as determined by creatinine-indexed urinary 8-epi-PGF2alpha levels. The effect of body mass index was minimally affected by blood glucose, and diabetes and may suggest an important role of oxidative stress in the deleterious impact of obesity on cardiovascular disease.

A Randomized Trial Comparing a Very Low Carbohydrate Diet and a Calorie-Restricted Low Fat Diet on Body Weight and Cardiovascular Risk Factors in Healthy Women

Article

Apr 2003

Untested alternative weight loss diets, such as very low carbohydrate diets, have unsubstantiated efficacy and the potential to adversely affect cardiovascular risk factors. Therefore, we designed a randomized, controlled trial to determine the effects of a very low carbohydrate diet on body composition and cardiovascular risk factors. Subjects were randomized to 6 months of either an ad libitum very low carbohydrate diet or a calorie-restricted diet with 30% of the calories as fat. Anthropometric and metabolic measures were assessed at baseline, 3 months, and 6 months. Fifty-three healthy, obese female volunteers (mean body mass index, 33.6 +/- 0.3 kg/m(2)) were randomized; 42 (79%) completed the trial. Women on both diets reduced calorie consumption by comparable amounts at 3 and 6 months. The very low carbohydrate diet group lost more weight (8.5 +/- 1.0 vs. 3.9 +/- 1.0 kg; P < 0.001) and more body fat (4.8 +/- 0.67 vs. 2.0 +/- 0.75 kg; P < 0.01) than the low fat diet group. Mean levels of blood pressure, lipids, fasting glucose, and insulin were within normal ranges in both groups at baseline. Although all of these parameters improved over the course of the study, there were no differences observed between the two diet groups at 3 or 6 months. beta- Hydroxybutyrate increased significantly in the very low carbohydrate group at 3 months (P = 0.001). Based on these data, a very low carbohydrate diet is more effective than a low fat diet for short-term weight loss and, over 6 months, is not associated with deleterious effects on important cardiovascular risk factors in healthy women.

Impact of Weight Loss on Inflammatory Proteins and Their Association With the Insulin Resistance Syndrome in Morbidly Obese Patients

Article

Jun 2003
ARTERIOSCL THROM VAS

Obesity is closely linked to the insulin resistance syndrome (IRS), type 2 diabetes, and cardiovascular disease, the primary cause of morbidity and mortality in these patients. Elevated levels of C-reactive protein (CRP) and interleukin-6 (IL-6), indicating chronic subclinical inflammation, have been associated with features of the IRS and incident cardiovascular disease. We studied the cross-sectional and longitudinal relation of CRP, IL-6, and tumor necrosis factor-alpha (TNF-alpha) with features of the IRS in 37 morbidly obese patients with different stages of glucose tolerance before and 14 months after gastric surgery. Weight loss after gastric surgery induced a significant shift from diabetes (37% vs 3%) to impaired glucose tolerance (40% vs 33%) and normal glucose tolerance (23% vs 64%). The baseline concentration of IL-6 was correlated with TNF-alpha (r=0.59, P<0.01) and CRP (r=0.44, P<0.05) levels. TNF-alpha, IL-6, and CRP were significantly correlated with insulin resistance estimated by the homeostatic model assessment (r=0.48, P<0.05; r=0.56, P<0.01; and r=0.35, P<0.05, respectively). Concentrations of CRP and IL-6 decreased after weight loss (median, 8.6 and interquartile range, 2.7/14.5 vs 2.5 and 1.2/4.1 mg/L; P<0.006, and 5.13 and 2.72/12.15 vs 3.95 and 1.97/5.64 pg/mL, P<0.02, respectively), whereas serum levels of TNF-alpha remained unchanged (8.6 and 6.3/18.8 vs 11.7 and 5.8/17.2 pg/mL; NS.). Multiple regression analysis revealed that the decrease in insulin resistance remained independently and significantly correlated with the decrease in IL-6 concentrations (P<0.01) and the decrease in body mass index with the decrease in CRP (P<0.05), respectively. Weight loss in morbidly obese patients induces a significant decrease of CRP and IL-6 concentrations in association with an improvement of the IRS.

A Low-Carbohydrate as Compared with a Low-Fat Diet in Severe Obesity

Article

Jun 2003
NEW ENGL J MED

The effects of a carbohydrate-restricted diet on weight loss and risk factors for atherosclerosis have been incompletely assessed. We randomly assigned 132 severely obese subjects (including 77 blacks and 23 women) with a mean body-mass index of 43 and a high prevalence of diabetes (39 percent) or the metabolic syndrome (43 percent) to a carbohydrate-restricted (low-carbohydrate) diet or a calorie- and fat-restricted (low-fat) diet. Seventy-nine subjects completed the six-month study. An analysis including all subjects, with the last observation carried forward for those who dropped out, showed that subjects on the low-carbohydrate diet lost more weight than those on the low-fat diet (mean [+/-SD], -5.8+/-8.6 kg vs. -1.9+/-4.2 kg; P=0.002) and had greater decreases in triglyceride levels (mean, -20+/-43 percent vs. -4+/-31 percent; P=0.001), irrespective of the use or nonuse of hypoglycemic or lipid-lowering medications. Insulin sensitivity, measured only in subjects without diabetes, also improved more among subjects on the low-carbohydrate diet (6+/-9 percent vs. -3+/-8 percent, P=0.01). The amount of weight lost (P<0.001) and assignment to the low-carbohydrate diet (P=0.01) were independent predictors of improvement in triglyceride levels and insulin sensitivity. Severely obese subjects with a high prevalence of diabetes or the metabolic syndrome lost more weight during six months on a carbohydrate-restricted diet than on a calorie- and fat-restricted diet, with a relative improvement in insulin sensitivity and triglyceride levels, even after adjustment for the amount of weight lost. This finding should be interpreted with caution, given the small magnitude of overall and between-group differences in weight loss in these markedly obese subjects and the short duration of the study. Future studies evaluating long-term cardiovascular outcomes are needed before a carbohydrate-restricted diet can be endorsed.

Increase in intranuclear nuclear factor κB and decrease in inhibitor κB in mononuclear cells after a mixed meal: Evidence for a proinflammatory effect

Article

May 2004

In view of the stimulatory effect of glucose on reactive oxygen species (ROS) generation, we investigated the possibility that a mixed meal stimulates ROS generation and possibly induces concomitant proinflammatory changes. The objective was to determine whether the intake of a 900-kcal mixed meal induces an increase in ROS generation by leukocytes and an inflammatory response at the cellular level. Nine normal-weight subjects were given a 900-kcal mixed meal, and 8 normal-weight subjects were given 300 mL water after an overnight fast. Blood samples were collected at 0, 1, 2, and 3 h. ROS generation by mononuclear cells and polymorphonuclear leukocytes and the expression of p47(phox) subunit were measured. Intranuclear nuclear factor kappaB (NF-kappaB) binding and the expression of inhibitor kappaBalpha (IkappaBalpha), IkappaB kinase alpha (IKKalpha), and IkappaB kinase beta (IKKbeta) were measured. Plasma concentrations of C-reactive protein (CRP) and soluble intercellular adhesion molecule were also measured. ROS generation by mononuclear cells and polymorphonuclear leukocytes and p47(phox) expression increased significantly. The expression of IKKalpha and IKKbeta and DNA-binding activity of NF-kappaB increased significantly, whereas IkappaBalpha expression decreased. Plasma CRP concentrations increased. The intake of 300 mL water did not induce a change in any of the above indexes. These data show that the intake of a mixed meal results in significant inflammatory changes characterized by a decrease in IkappaBalpha and an increase in NF-kappaB binding, plasma CRP, and the expression of IKKalpha, IKKbeta, and p47(phox) subunit. These proinflammatory changes are probably relevant to the state of chronic hypertension and obesity and to its association with atherosclerosis.

Dietary Fiber and C-Reactive Protein: Findings from National Health and Nutrition Examination Survey Data

Article

Jun 2004

A higher intake of dietary fiber may decrease the risk of developing cardiovascular disease. We examined the association between dietary fiber and serum concentration of C-reactive protein (CRP), a possible predictor of cardiovascular events, using data from the National Health and Nutrition Examination Survey 1999-2000. Among 3920 participants > or = 20 y old, dietary fiber intake was inversely associated with serum CRP concentration. The odds ratio (OR) for increased CRP concentration (>3.0 mg/L) was 0.49 (95% CI 0.37-0.65; P for trend < 0.001) for the highest quintile of fiber intake compared with the lowest. Adjustment for age, gender, race, education, smoking, physical activity, BMI, total energy, and fat intake resulted in a slight attenuation (OR 0.59; CI 0.41-0.85; P for trend = 0.006). Excluding participants with cardiovascular conditions, diabetes, or cancer did not alter the results. Our findings indicate that fiber intake is independently associated with serum CRP concentration and support the recommendation of a diet with a high fiber content.

A Low-Carbohydrate, Ketogenic Diet versus a Low-Fat Diet To Treat Obesity and Hyperlipidemia A Randomized, Controlled Trial

Low Carbohydrate, High Fat Diet Increases C-Reactive Protein during Weight Loss

Abstract

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