To assess whether selenium and carboxymethyl-lysine (CML), two biomarkers of oxidative stress, are independent predictors of anemia in older, community-dwelling adults.
Plasma selenium, CML, folate, vitamin B12, testosterone, and markers of iron status and inflammation were measured at baseline in 1,036 adults, ≥65 years, in the InCHIANTI Study, a population-based cohort study of aging in Tuscany, Italy, and examined in relationship to prevalent anemia and incident anemia over 6 years of follow-up.
At enrollment, 11.6% of participants were anemic. Of 472 participants who were non-anemic at enrollment 72 (15.3%) developed anemia within 6 years of follow-up. At enrollment, plasma CML in the highest quartile (>425 ng/mL) and plasma selenium in the lowest quartile (<66.6 μg/L) predicted incident anemia (Hazards Ratio [H.R.] 1.67, 95% Confidence Interval [C.I.] 1.07–2.59, P = 0.02; H.R. 1.55, 95% C.I.1.01–2.38, P = 0.05, respectively) in a multivariate Cox proportional hazards model that adjusted for age, education, body mass index, cognition, inflammation, red cell distribution width, ferritin, vitamin B12, testosterone, and chronic diseases.
Elevated plasma carboxymethyl-lysine and low plasma selenium are long-term independent predictors of anemia among older community-dwelling adults. These findings support the idea that oxidative stress contributes to the development of anemia.
advanced glycation end products; aging; anemia; carboxymethyl-lysine; oxidative stress; selenium
This study investigated the role of L-arginine supplementation to undernourished and Cryptosporidium parvum-infected suckling mice.
The following regimens were initiated on the 4th day of life and given subcutaneously daily: either 200mM of L-arginine or PBS for the C. parvum-infected controls. L-arginine-treated mice were grouped to receive either 20mM of NG-nitroarginine-methyl-ester (L-NAME) or PBS. Infected mice received orally 106 excysted-C. parvum oocysts on day 6 and were euthanized on day 14th at the infection peak.
L-arginine improved weight gain compared to the untreated infected controls. L-NAME profoundly impaired body weight gain as compared to all other groups. Cryptosporidiosis was associated with ileal crypt hyperplasia, villus blunting, and inflammation. L-arginine improved mucosal histology following infection. L-NAME abrogated these arginine-induced improvements. Infected control mice showed an intense arginase expression, which was even greater with L-NAME. L-arginine reduced parasite burden, an effect that was reversed by L-NAME. C. parvum infection increased urine NO3-/NO2- concentration when compared to uninfected controls, which was increased by L-arginine supplementation, an effect that was also reversed by L-NAME.
These findings show a protective role of L-arginine during C. parvum infection in undernourished mice with involvement of arginase I and nitric oxide synthase enzymatic actions.
Cryptosporidium parvum; diarrhea; malnutrition; arginine; growing mice
High sugar intake increases heart disease risk in humans. In animals, sugar intake accelerates heart failure development via increased reactive oxygen species (ROS). Glucose 6-phosphate dehydrogenase (G6PD) can fuel ROS production by providing NADPH for superoxide generation by NADPH oxidase. On the other hand, G6PD also facilitates ROS scavenging via the glutathione pathway. We hypothesized that high sugar intake would increase flux through G6PD to increase myocardial [NADPH] and ROS, and accelerate cardiac dysfunction and death.
Research Methods & Procedures
Six-week old TO-2 hamsters, a nonhypertensive model of genetic cardiomyopathy caused by a δ-sarcoglycan mutation, were fed a long-term diet of either high starch or high sugar (57% of energy from sucrose+fructose).
After 24 weeks, δ-sarcoglycan deficient animals displayed expected decreases in survival and cardiac function associated with cardiomyopathy (ejection fraction: control=68.7±4.5%; TO-2 starch=46.1±3.7, p<0.05 TO-2 starch vs control; TO-2 sugar=58.0±4.2%, N.S. vs TO-2 starch or control; median survival: TO-2 starch=278 days, TO-2 sugar=318 days, P=0.133). Although we expected high sugar intake to exacerbate cardiomyopathy, surprisingly there was no further decrease in ejection fraction or survival with high sugar compared to starch in cardiomyopathic animals. Cardiomyopathic animals had systemic and cardiac metabolic abnormalities (elevated serum lipids and glucose, and decreased myocardial oxidative enzymes) which were unaffected by diet. High sugar intake increased myocardial superoxide, but [NADPH] and lipid peroxidation were unaffected.
A sugar enriched diet did not exacerbate ventricular function, metabolic abnormalities, or survival in heart failure despite an increase in NADPH and superoxide production.
heart failure; reactive oxygen species; δ-sarcoglycan; diet; sugar; fructose; sucrose
Dynapenia (pronounced dahy-nuh-pē-nē-a, Greek translation for poverty of strength, power, or force) is the age-associated loss of muscle strength that is not caused by neurologic or muscular diseases. Dynapenia predisposes older adults to an increased risk for functional limitations and mortality. For the past several decades, the literature has largely focused on muscle size as the primary cause of dynapenia; however, recent findings have clearly demonstrated that muscle size plays a relatively minor role. Conversely, subclinical deficits in the structure and function of the nervous system and/or impairments in the intrinsic force-generating properties of skeletal muscle are potential antecedents to dynapenia. This review highlights in the contributors to dynapenia and the etiology and risk factors that predispose individuals to dynapenia. In addition, we address the role of nutrition in the muscular and neurologic systems for the preservation of muscle strength throughout the life span.
Aging; Strength; Weakness; Function; Muscle; Disability; Sarcopenia; Dynapenia
We previously reported an association between prenatal exposure to airborne PAH and lower birth weight, birth length and head circumference. The main goal of the present analysis was to assess the possible impact of co-exposure to PAH-containing of barbecued meat consumed during pregnancy on birth outcomes.
The birth cohort consisted of 432 pregnant women who gave birth at term (>36 weeks of gestation). Only non-smoking women with singleton pregnancies, 18-35 years of age, and who were free from chronic diseases such as diabetes and hypertension were included in the study. Detailed information on diet over pregnancy was collected through interviews and the measurement of exposure to airborne PAHs was carried out by personal air monitoring during the second trimester of pregnancy. The effect of barbecued meat consumption on birth outcomes (birthweight, length and head circumference at birth) was adjusted in multiple linear regression models for potential confounding factors such as prenatal exposure to airborne PAHs, child’s sex, gestational age, parity, size of mother (maternal prepregnancy weight, weight gain in pregnancy) and prenatal environmental tobacco smoke (ETS).
The multivariable regression model showed a significant deficit in birthweight associated with barbecued meat consumption in pregnancy (coeff = −106.0 g; 95%CI: −293.3, −35.8); The effect of exposure to airborne PAHs was about the same magnitude order (coeff. = −164.6 g; 95%CI: −172.3, − 34.7). Combined effect of both sources of exposure amounted to birth weight deficit of 214.3 g (95%CI: −419.0, − 9.6). Regression models performed for birth length and head circumference showed similar trends but the estimated effects were of borderline significance level. As the intake of barbecued meat did not affect the duration of pregnancy, the reduced birthweight could not have been mediated by shortened gestation period.
In conclusion, the study results provided epidemiologic evidence that prenatal PAH exposure from diet including grilled meat might be hazardous for fetal development.
barbecued meat; pregnancy; birth weight; birth cohort study
Vitamin D deficiency is common in tuberculosis (TB) and this may modulate immune responses.
To determine vitamin D status in patients with TB and examine sources of vitamin D in Tbilisi, Georgia.
Research Methods and Procedures
We measured plasma 25-hydroxyvitamin D (25(OH)D) and dietary vitamin D intake in pulmonary TB patients (n=85) in Tbilisi, Georgia. To determine the impact of season on vitamin D status, we tested in vitro conversion of 7-dehydrocholesterol (7-DHC) to previtamin D3 after sunlight exposure.
In TB subjects, mean plasma 25(OH)D concentrations were 14.5 ± 7.0 ng/mL, and vitamin D insufficiency (25(OH)D < 30 ng/mL) occurred in 97% of subjects. Dietary sources of vitamin D were mainly fish, eggs, and butter. Daily intake was well below recommended daily intakes in TB subjects (172 IU + 196 IU). The conversion of 7-DHC to previtamin D3 was undetectable between October to March, and highest in June and July between 11:00 and 14:00 h.
Insufficient vitamin D dietary intake and limited production of vitamin D from sunlight during the majority of the year, may explain the high prevalence of vitamin D insufficiency TB patients in Tbilisi.
cholecalciferol; 7-dehydrocholesterol; dietary intake
Deficient 25-hydroxyvitamin D [25(OH)D] levels are associated with cardiovascular disease (CVD) events and mortality. Both 25(OH)D deficiency and stroke are more prevalent among blacks. We examined whether low 25(OH)D contributes to the excess risk of fatal stroke in blacks compared to whites.
Research Methods and Procedures
The Third National Health and Nutrition Examination Survey, a probability sample of US civilians, measured 25(OH)D levels and CVD risk factors between 1988–1994. Vital status through December 2006 was obtained via linkage with the National Death Index. Among white and black adults without CVD reported at baseline (n=7981), Cox regression models were fit to estimate hazard ratios (HR) for fatal stroke by 25(OH)D status and race.
During a median of 14.1 years, there were 116 and 60 fatal strokes among whites and blacks respectively. The risk of fatal stroke was greater in blacks compared to whites in models adjusted for socio-economic status and CVD risk factors, [HR 1.60 (95% CI 1.01–2.53)]. Mean baseline 25(OH)D levels were significantly lower in blacks compared to whites (19.4 vs 30.8 ng/mL, respectively). In multivariable-adjusted models, deficient 25(OH)D levels <15 ng/mL were associated with fatal stroke among whites [HR 2.13 (1.01–4.50)] but not blacks [HR 0.93 (0.49–1.80)].
Vitamin D deficiency was associated with increased risk of stroke death in whites but not blacks. Although blacks had a higher rate of fatal stroke compared to whites, the low 25(OH)D levels in blacks were unrelated to stroke incidence and therefore 25(OH)D levels did not explain this excess risk.
vitamin D; stroke; racial differences
Over the past three decades obesity has become a major public health crisis in the United States. The prevalence of obesity in the United States and in other parts of the World has led to the new word, globesity, now being used to describe the problem. As a result of this increased emphasis on understanding the causes and consequences of obesity, novel theories have stimulated new research aimed to prevent, intervene with, and ameliorate the effects and reduce the incidence and medical consequences of globesity. One theory that has gained popularity in recent years, which we described and analyzed in our previous paper Neurobiology of Food Addiction, is based on the idea that excessive intake of highly-palatable foods shares similarities with the effects on brain and behavior that are seen with some drugs of abuse. While this theory is not new, empirically-based translational research has only recently provided strong support for this hypothesis. In this article, we review the present state of the science in this area and describe a variety of newer clinical and preclinical works that shed light on innovative and interesting overlaps between excessive palatable food intake and drug use.
Addiction; Dopamine; Food intake; Obesity; Overeating
This pilot study was designed to determine if metabolic effects in different brain regions (left and right parietal lobes, midbrain) due to 3 days of food consumption without methionine or cysteine could be detected by proton magnetic resonance spectroscopy (MRS).
Research Methods & Procedures
Healthy individuals aged 18-36 y (n=8) were studied by MRS after receiving diet with adequate sulfur amino acids (SAA) or with zero SAA for 3 days. Pulse sequences were used to selectively measure glutathione (GSH) and linear combination modeling (LCM) of spectra was used to measure other high abundance brain metabolites, and expressed relative to creatine (Cr).
Although dietary SAA are required to maintain glutathione (GSH), the 3-d SAA insufficiency resulted in no significant change in GSH/Cr in the three brain regions. Principal component analysis of 16 metabolites measured by LCM showed that the metabolic pattern in the midbrain, but not the parietal lobes, was distinguished according to the dietary SAA. Multivariate statistical analysis showed that the major discriminating factors were signals of glutamate/Cr, (glutamate+glutamine)/Cr, and myo-inositiol/Cr. Correlation analyses between midbrain metabolites and GSH-related metabolites in plasma showed that midbrain glutamate/Cr had an inverse correlation with plasma cystine.
The data show that MRS is a non-invasive tool suitable for nutritional assessment and suggest that nutritional imbalance caused by 3-d of sulfur amino acid-free food more selectively affects midbrain than the parietal lobes.
Brain metabolism; oxidative stress; amino acid metabolism; nutritional assessment; protein malnutrition; glutathione
Roux-en-Y gastric bypass (RYGB) surgery is the most common surgical intervention for long-term weight loss in morbidly obese patients. By reducing obesity-associated hyperfiltration, diabetes, and hypertension, RYGB is touted to stabilize if not prevent progression of chronic renal disease. To test this, we compare renal histology of diet-induced obese rats that have undergone RYGB surgery to pair-fed and sham obese controls.
Research Methods and Procedures
Sprague-Dawley rats, fed a high fat, low-oxalate diet to induce gross obesity, were randomized to RYGB (n=6), GI-intact sham-operated obese controls (Sham, n=4), or GI-intact sham-operated obese pair-fed rats (Fed, n=8). Daily body weight and food intake were recorded. On post-operative day 42, renal histology and immunohistochemistry was examined. Renal pathology was assessed by a categorical glomerular lesion score and a quantitative glomerular/tubular scoring system by experienced veterinary pathologists. Osteopontin (OPN) and ED-1 (monocyte/macrophage cell) staining were estimated on percentage of stained area and number of counted cells/high power field respectively.
Compared to sham and fed controls, RYGB rats had significant reductions in body weight (p<0.001), more glomerular lesions (p=0.02), and received higher glomerular and tubular lesion scores (p<0.01). RYGB rodents had significantly stronger staining for OPN within the inner medullary region (p<0.005) and ED-1 within the outer medullary region (P<0.02) compared to sham and fed controls.
In this diet-induced obese rat model, RYGB is associated with chronic glomerulosclerosis and tubulointerstitial nephritis, confirmed by histology and immunohistochemistry. Prospective studies to better define the injurious mechanisms in this model are planned.
morbid obesity; interstitial nephritis; gastric bypass; oxalate
Lower brain glucose metabolism is present before the onset of clinically-measurable cognitive decline in two groups of people at risk of Alzheimer’s disease (AD) - carriers of apoE4, and in those with a maternal family history of AD. Supported by emerging evidence from in vitro and animal studies, these reports suggest that brain hypometabolism may precede and contribute to the neuropathological cascade leading cognitive decline in AD. The reason for brain hypometabolism is unclear but may include defects in glucose transport at the blood-brain barrier, glycolysis, and/or mitochondrial function. Methodological issues presently preclude knowing with certainty whether or not aging in the absence of cognitive impairment is necessarily associated with lower brain glucose metabolism. Nevertheless, aging appears to increase the risk of deteriorating systemic control of glucose utilization which, in turn, may increase the risk of declining brain glucose uptake, at least in some regions. A contributing role of deteriorating glucose availability to or metabolism by the brain in AD does not exclude the opposite effect, i.e. that neurodegenerative processes in AD further decrease brain glucose metabolism because of reduced synaptic functionality and, hence, reduced energy needs, thereby completing a vicious cycle. Strategies to reduce the risk of AD by breaking this cycle should aim to – (i) improve insulin sensitivity by improving systemic glucose utilization, or (ii) bypass deteriorating brain glucose metabolism using approaches that safely induce mild, sustainable ketonemia.
Glucose; ketones; brain; aging; Alzheimer’s disease; PET; insulin; cognition; mitochondria
We recently identified an inverse relationship between systolic blood pressure (SBP) and serum 16α-hydroxyestrone, a metabolite of 17β-estradiol, in postmenopausal women. Formation of 16α-hydroxyestrone is catalyzed primarily by CYP1A2, a cytochrome P450 enzyme. The objective of this study was to evaluate the relationships between known modifiers of CYP1A2 activity and serum 16α-hydroxyestrone in postmenopausal women. We hypothesized that fruits, vegetables, and grains, which contain more soluble fiber (a known inducer of CYP1A2) as a proportion of total fiber, would be more positively associated with serum 16α-hydroxyestrone than legumes, which contain less soluble fiber as a proportion of total fiber.
Materials and Methods
Serum from a population-based sample of 42 postmenopausal women aged 55–69 living in Cook County, Illinois, was assayed for 16α-hydroxyestrone using mass spectrometry. Ordinal logistic regression was used to evaluate the cross-sectional relationship between dietary fiber and serum 16α-hydroxyestrone after adjusting for multiple covariates.
Relative to dietary fiber from legumes, dietary fiber from fruits and vegetables was associated with a greater log odds (B = 0.201, p = 0.036) of having higher serum concentrations of 16α-hydroxyestrone. The log odds of having higher serum concentrations of 16α-hydroxyestrone was also lower among African-American women (B = −2.300, p = .030) compared to white women.
These results are consistent with previous studies demonstrating a negative relationship between SBP and dietary fruits and vegetables and a positive relationship between African-American race and SBP. Further research is needed regarding dietary factors that may influence the serum concentration of 16α-hydroxyestrone.
nutrition; fiber; fruits; vegetables; estrogen; metabolism; blood pressure
The continually increasing rate of myocardial infarction (MI) in the Western world at least partly can be explained by a poor diet lacking in green vegetables, fruits, and fish, and enriched in food that contains saturated fat. In contrast, a number of epidemiological studies provide strong evidence highlighting the cardioprotective benefits of the Mediterranean diet enriched in green vegetables, fruits, fish and grape wine. Regular consumption of these products leads to an accumulation of nitrate/nitrite/NO•, polyunsaturated fatty acids (PUFA), and polyphenolic compounds, such as resveratrol, in the human body. Studies have confirmed that these constituents are bioactive exogenous mediators, which induce strong protection against MI. The aim of this review is to provide a critical, in-depth analysis of the cardioprotective pathways mediated by nitrite/NO•, PUFA, and phenolic compounds of grape wines discovered in the recent years, including cross-talk between different mechanisms and compounds. Overall, these findings may facilitate the design and synthesis of novel therapeutic tools for the treatment of MI.
The objective of the study was to evaluate LINE-1 methylation as an intermediate biomarker for the effect of folate and vitamin B12 on the occurrence of higher grades of cervical intraepithelial neoplasia (CIN 2+).
Study included 376 women who tested positive for HR-HPVs and were diagnosed with CIN 2+ (cases) or ≤ CIN 1 (non-cases). CIN 2+ (yes/no) was the dependent variable in logistic regression models that specified the degree of LINE-1 methylation of peripheral blood mononuclear cells (PBMCs) and of exfoliated cervical cells (CCs) as the independent predictors of primary interest. In analyses restricted to non-cases, PBMC LINE-1 methylation (≥70% vs. <70%) and CC LINE-1 methylation (≥54% vs. <54%) were the dependent variables in logistic regression models that specified the circulating concentrations of folate and vitamin B12 as the primary independent predictors.
Women in the highest tertile of PBMC LINE-1 methylation had 56% lower odds of being diagnosed with CIN 2+ (OR = 0.44; 95% CI, 0.24-0.83; P = 0.011) while there was no significant association between degree of CC LINE-1 methylation and CIN 2+ (OR = 0.86; 95% CI, 0.51-1.46; P = 0.578). Among non-cases, women with supra-physiologic concentrations of folate (>19.8 ng/mL) and sufficient concentrations of plasma vitamin B12 (≥ 200.6 ng/mL) were significantly more likely to have highly methylated PBMCs compared to women with lower folate and lower vitamin B12 (OR = 3.92; 95% CI, 1.06-14.52; P = 0.041). None of the variables including folate and vitamin B12 were significantly associated with CC LINE-1 methylation.
These results suggest that a higher degree of LINE-1 methylation in peripheral blood mononuclear cells, a one-carbon nutrient related epigenetic alteration, is associated with a lower risk of developing cervical intraepithelial neoplasia.
methylation; cervical; neoplasia
Leptin was discovered in 1994 as a hormone produced by adipose tissue with a modulatory effect on feeding behavior and weight control. Recently, the stomach has been identified as an important source of leptin and growing evidence has shown diverse functions for leptin in the gastrointestinal tract.
Using leptin as a keyword in PubMed, more than 17 000 articles were identified, of which more than 500 articles were related to the role of leptin in the gastrointestinal tract. Available abstracts were reviewed and more than 200 original articles were reviewed in detail.
The available literature demonstrated that leptin can modulate several important functions of the gastrointestinal tract. Leptin interacts with the vagus nerve and cholecystokinin to delay gastric emptying and has a complex effect on motility of the small bowel. Leptin modulates absorption of macronutrients in the gastrointestinal tract differentially in physiologic and pathologic states. In physiologic states, exogenous leptin has been shown to decrease carbohydrate absorption and to increase the absorption of small peptides by the PepT1 di-/tripeptide transporter. In certain pathologic states, leptin has been shown to increase absorption of carbohydrates, proteins, and fat. Leptin has been shown to be upregulated in the colonic mucosa in patients with inflammatory bowel disease. Leptin stimulates gut mucosal cell proliferation and inhibits apoptosis. These functions have led to speculation about the role of leptin in tumorigenesis in the gastrointestinal tract, which is complicated by the multiple immunoregulatory effects of leptin.
Leptin is an important modulator of major aspects of gastrointestinal tract functions, independent of its more well-described roles in appetite regulation and obesity.
Colon; Inflammation; Intestine; Leptin; Motility; Nutrient absorption
Esophageal cancer consists of two distinct types –esophageal adenocarcinoma (EAC) and squamous cell carcinoma (SCC), both of which differ significantly in their etiology. Freeze dried black raspberry (BRB) has been consistent in its ability to modulate the biomarkers and reduce the incidence of carcinogen-induced SCC in rats. In our previous studies in the esophagoduodenal anastomosis (EDA) model, we have shown that the early modulation of Manganese Superoxide dismutase (MnSOD) significantly correlates with the development of reflux-induced EAC in rats. In this study we looked at the short-term effects of a BRB supplemented diet on the modulation of antioxidant enzymes in reflux-induced esophagitis.
Male SD rats (8 wo; n=3–5) were randomized into 3 groups- sham-operated, fed control AIN-93M diet (SH-CD), EDA operated and fed either control diet (EDA-CD) or 2.5% (w/w) BRB diet (EDA-BRB). The effect of both reflux and dietary supplementation was analyzed 2 and 4 weeks after EDA surgery.
Animals in EDA groups had significantly lower weight gain and diet intake compared to SH-CD (p<0.05). The sham operated animals, received an average esophagitis score of 0.1 ± 0.1, this increased significantly in EDA –CD animals to 1.8 ± 0.14 (p< 0.001 vs SH-CD) and in EDA-BRB group to 1.7 ± 0.06 (p< 0.001 vs SH-CD), with BE changes also present. However, dietary supplementation of BRB did not alter or ameliorate the grade of esophagitis or the induction of BE. BRB diet caused a 43% increase in MnSOD levels compared to EDA-CD (0.73 ± 0.16; p=0.09), however, this effect was not statistically significant and at 4 weeks, EDA-CD (0.58 ±0.12) showed an increase in MnSOD expression compared to SH-CD (0.34 ± 0.01).
In conclusion, our data suggests that dietary BRB does not increase the levels of cellular antioxidant enzymes or reduce the levels of lipid peroxidation compared to a control diet, in a short-term study of gastroesophageal reflux induction in the EDA animal model. However, it remains to be tested whether this is indicative of its ineffectiveness to inhibit reflux-induced EAC incidence over long-term.
Black raspberry; reflux-esophagitis; barrett’s esophagus; esophagoduodenal anastomosis; esophageal adenocarcinoma; superoxide dismutase; cellular antioxidant enzymes
Oxidation of plasma cysteine/cystine (Cys/CySS) redox potential (EhCySS) has been associated with risk factors for cardiovascular disease in humans. Cys and CySS are derived from dietary sulfur amino acids (SAA), but the specific effects of SAA depletion and repletion on Cys/CySS redox indices are unknown. The present study examined the effect of dietary SAA intake level on free Cys, free CySS and EhCySS in human plasma under fasting conditions.
Research Methods and Procedures
Healthy individuals aged 18–36 y (n=13) were equilibrated to foods providing the RDA for SAA and then fed chemically defined diets without SAA (0 mg·kg−1·d−1; n=13) followed by SAA at levels approximating the mean (56 mg·kg−1·d−1; n=8) or 99th percentile (117 mg·kg−1·d−1; n=5) intake levels of Americans. Fasting plasma samples were collected daily during 4-d study periods and analyzed for free Cys, free CySS and the EhCySS.
The SAA-free diet significantly (p<0.05) decreased plasma free Cys concentrations and oxidized EhCySS values after 4 days of SAA depletion. With SAA repletion at 56 mg·kg−1·d− 1, plasma free Cys increased significantly and values for EhCySS became more reducing. Administration of a diet providing a higher dose of SAA (117 mg·kg−1·d−1) resulted in a significantly higher level of free Cys and a more reducing EhCySS.
These results show that free Cys and Cys/CySS redox potential (EhCySS) in fasting plasma are affected by dietary SAA intake level in humans. Significant changes occur slowly over 4 days with insufficient SAA intake, but rapidly (after 1 day) with repletion.
Oxidative stress; amino acid balance; cardiovascular disease; methionine
Green tea (Camellia sinensis) has shown to exert cardio-protective benefits in observational studies. The objective of this clinical trial was to assess the effects of green tea on features of metabolic syndrome and inflammation in obese subjects.
We conducted a randomized controlled trial in obese subjects with metabolic syndrome. Thirty-five subjects [age (mean±SE) 42.5±1.7 years, BMI 36.1±1.3 kg/m2] completed the 8-week study and were randomly assigned to receive green tea (4 cups/day), green tea extract (2 capsules and 4 cups water/day), or no treatment (4 cups water/day). Both the beverage and extract groups had similar dosing of epigallocatechin-3-gallate (EGCG), the active green tea polyphenol. Fasting blood samples were collected at screening, four, and eight weeks of the study.
Green tea beverage or extract supplementation did not significantly alter features of metabolic syndrome or biomarkers of inflammation including adiponectin, C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-1β (IL-1β), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), leptin, or leptin:adiponectin ratio. However, both green tea beverage and extracts significantly reduced plasma serum amyloid alpha (SAA) versus no treatment (p<0.005).
This study suggests that the daily consumption of green tea beverage or extracts for 8 weeks was well tolerated but did not affect the features of metabolic syndrome. However, green tea significantly reduced plasma SAA, an independent CVD risk factor, in obese subjects with metabolic syndrome.
Green tea; Inflammation; Serum amyloid A; Metabolic syndrome
Sepsis, severe injury, and cancer are associated with loss of muscle mass. Muscle wasting in these conditions is mainly caused by increased proteolysis, at least in part regulated by NF-kB. Despite recent progress in the understanding of mediators and mechanisms involved in muscle wasting, effective and universally accepted treatments by which muscle atrophy can be prevented or reversed are still lacking. Here, we review recent evidence suggesting that curcumin (diferuloylmethane), a component of the spice turmeric, may prevent loss of muscle mass during sepsis and endotoxemia and may stimulate muscle regeneration after traumatic injury. Curcumin has been part of the traditional Asian medicine for centuries, mainly because of its anti-inflammatory properties. Studies suggest that inhibition of NF-kB is one of the mechanisms by which curcumin exerts its ant-inflammatory effects. Curcumin is easily accessible, inexpensive, and non-toxic even at high doses, and may therefore offer an important treatment modality in muscle wasting and injury. It should be noted, however, that the muscle-sparing effects of curcumin are not universally accepted, and more studies are therefore needed to further test the role of curcumin in the prevention and treatment of muscle wasting.
Muscle atrophy; proteolysis; NF-kB; catabolic
Animal studies have demonstrated that dietary supplementation with flaxseed oil inhibits colorectal cancer growth. Recent data indicate that walnuts have strong antiproliferative properties against colon cancer cells in vitro but no previous study has assessed the effects of walnuts in vivo or performed a joint evaluation of flaxseed oil and walnuts. The aim of the present study was to examine the effect of dietary walnuts on colorectal cancer in vivo and to comparatively evaluate their efficacy in relation to flaxseed oil.
HT-29 human colon cancer cells were injected in 6-wk-old female nude mice. After a 1-wk acclimation period, mice (n = 48) were randomized to diets containing ~ 19% of total energy from walnuts, flaxseed oil, or corn oil (control) and were subsequently studied for 25 d.
Tumor growth rate was significantly slower in walnut-fed and flaxseed-fed mice compared with corn oil-fed animals (P < 0.05) by 27% and 43%, respectively. Accordingly, final tumor weight was reduced by 33% and 44%, respectively (P < 0.05 versus control); the differences between walnut and flaxseed diets did not reach significance. We found no differences among groups in metabolic and hormonal profile, serum antioxidant capacity, or inflammation (P > 0.05). However, walnuts and flaxseed oil significantly reduced serum expression levels of angiogenesis factors, including vascular endothelial growth factor (by 30% and 80%, respectively), and approximately doubled total necrotic areas despite smaller tumor sizes (P < 0.05 versus control). Dietary walnuts significantly decreased angiogenesis (CD34 staining; P = 0.017 versus control), whereas this effect did not reach significance in the flaxseed oil group (P = 0.454 versus control).
We conclude that walnuts in the diet inhibit colorectal cancer growth by suppressing angiogenesis. Further studies are needed to confirm our findings in humans and explore underlying mechanisms.
Nuts; Linseed; Colon cancer; Xenograft; VEGF
Elevated plasma total homocysteine (tHcy) is a risk factor for a variety of human diseases. Homocysteine is formed from methionine and has two primary metabolic fates: remethylation to form methionine or commitment to the transulfuration pathway by the action of cystathionine β-synthase (CBS). Here, we have examined the metabolic response in mice of a shift from a methionine-replete (M+) to a methionine-free (M−) diet.
We found that shifting three-month old C57BL6 mice to a M− diet caused a transient increase in tHcy, as well as an increase in the tHcy/methionine ratio. Since CBS is a key regulator of tHcy, we examined CBS protein levels and found that within 3 days on methionine-deficient diet, animals had a 50% reduction in the levels of liver CBS protein and enzyme activity. Examination of CBS mRNA and studies of transgenic animals that express CBS from a heterologous promoter indicate that this reduction is occurring post-transcriptionally. Loss of CBS protein was unrelated to intracellular levels of S-adenosylmethionine, a known regulator of CBS activity and stability.
Our results imply that methionine deprivation induces a metabolic state in which methionine is effectively conserved in tissue by shutdown of the transsulfuration pathway via an S-adenosylmethionine-independent mechanism that signals a rapid down-regulation of CBS protein.
Metabolism; Genetics; Amino Acids; Cardiovascular Disease
Insulin is an important regulator of glucose, lipid and protein metabolism. It suppresses hepatic glucose and triglyceride production, inhibits adipose tissue lipolysis and whole-body and muscle proteolysis and stimulates glucose uptake in muscle. In this review we discuss what is currently known about the control of substrate metabolism by insulin in men and women. The data available so far indicate that women are more sensitive to insulin with regards to glucose metabolism (both in the liver and in muscle) whereas there are no differences between men and women in insulin action on lipolysis. Potential differences exist in the regulation of plasma triglyceride concentration and protein metabolism by insulin and in changes in insulin-action in response to stimuli (e.g., weight loss and exercise) that are known to alter insulin sensitivity. However, these areas have not been studied comprehensively enough to draw firm conclusions.
glucose uptake; hepatic glucose production; lipolysis; triglyceride secretion; triglyceride clearance; proteolysis
Associations between dietary glycemic load (GL) and cardiovascular disease (CVD) risk factors, including plasma lipoprotein/lipid levels, blood pressure (BP), and glucose metabolism factors, in the Women's Health Initiative Observational Study were examined.
A random sample of 878 Observational Study participants (postmenopausal women age 50 to 79 years) with baseline blood measures (647 White, 104 Black, 127 Hispanic) was included. Dietary GL was estimated from baseline food frequency questionnaires, which assessed dietary intake over the previous three months. At the baseline visit, participants completed demographic and health habit questionnaires, fasting blood samples were collected, anthropometric measurements were completed, and BP was assessed.
In all participants combined, GL was inversely associated with high-density lipoprotein (HDL) cholesterol (P for trend = 0.004) and positively associated with log10-transformed triglycerides (P = 0.008). While there were no statistically significant interactions of race/ethnicity with associations between GL and CVD risk factors, stratified results were suggestive, showing that GL was positively associated with total cholesterol (P = 0.018) and low-density lipoprotein (LDL) cholesterol (P = 0.038) in Hispanics. In Whites, there was a trend of reduced HDL cholesterol with higher GL (P = 0.003), while GL was positively associated with log10-transformed triglycerides (P = 0.015). Associations between GL and HDL cholesterol and GL and triglycerides also varied by BMI, although the interactions were not statistically significant.
Among these generally healthy postmenopausal women, GL was associated with HDL cholesterol and triglycerides. Suggestive effects of race/ethnicity and BMI on these associations need to be confirmed in larger studies.
Glycemic load; Glycemic index; Carbohydrate; Cardiovascular disease; Women's Health Initiative