Improving Adherence to a Mediterranean Ketogenic Nutrition Program for High-Risk Older Adults: A Pilot Randomized Trial.

(1) Background: Mediterranean ketogenic nutrition (MKN) may directly target multiple neurobiological mechanisms associated with dementia risk in older adults. Despite its promise, this type of nutrition can be challenging to learn and adhere to in a healthy manner. Our team used the National Institutes of Health Obesity Related Behavioral Intervention Trials (NIH ORBIT) model to develop and pilot a program to help older adults with memory concerns use MKN. (2) Methods: Using a two-arm, randomized design, we evaluated an MKN Adherence (MKNA) program compared to an MKN education (MKNE) program (N = 58). The primary difference between study arms involved the use of motivational interviewing (MI) strategies and behavior change techniques (BCT) only in the MKNA arm. Participants were included if they evidenced subjective memory concerns or objective memory impairment on the Montreal Cognitive Assessment (Score 19 ≤ 26). Primary outcomes examined included feasibility, acceptability, adherence, and clinical outcomes associated with the program. (3) Results: Overall, there was relatively high program completion in both groups, with 79% of participants completing the 6-week program. The recruitment protocol required adjustment but was successful in reaching the target sample size. Retention (82%) and session attendance (91%) were higher in the MKNA arm compared to the MKNE (retention = 72%; attendance = 77%). Overall, most participants in both groups rated the program as "excellent" using the client satisfaction questionnaire. Participants in the MKNA arm evidenced higher objective and self-reported adherence to MKN during the 6-week program. Further, there was some evidence of clinical benefits of the program, although these effects diminished as adherence decreased in the 3 months follow-up. (4) Discussion: This pilot trial demonstrated that the MKN program incorporating MI and BCT strategies may better engage and retain participants than a nutrition education program alone, although participants in both groups reported high satisfaction.

Improving Dietary Intake of Essential Nutrients Can Ameliorate Inflammation in Patients with Diabetic Foot Ulcers.

Diabetic foot ulcers (DFUs) are classified as chronic wounds and are one of the most common complications of diabetes. In chronic wounds, management of inflammation is a key step in treatment. Nutrition plays an important role in managing and controlling inflammation. This study evaluated the effects of nutrition supplementation and education on inflammatory biomarkers in patients with DFUs. Eligible patients with foot ulcers were randomly assigned to either a treatment (n = 15) or control group (n = 14). Both groups received standard care for wound treatment from the clinic; however, the treatment group was also provided with nutritional supplementation and education. Plasma concentrations of inflammatory biomarkers, namely C-reactive protein (CRP), interleukin 6 (IL6), interleukin 10 (IL10), and tristetraprolin (TTP), were evaluated at baseline and every four weeks, until complete wound closure had occurred or up to 12 weeks. The mean plasma concentration of IL6 significantly decreased in the treatment group (p = 0.001). The interaction between time and group was not statistically significant for the mean plasma concentrations of CRP, IL10, and TTP during the 12 weeks of the study. The results of this study showed the positive effects of nutritional intervention on controlling inflammation in DFU patients. More clinical trials with a larger population and longer duration of time are needed to confirm our results.

The Short-Term Effect of Prunes in Improving Bone in Men.

Osteoporosis is a major health concern in aging populations, where 54% of the U.S. population aged 50 and older have low bone mineral density (BMD). Increases in inflammation and oxidative stress play a major role in the development of osteoporosis. Men are at a greater risk of mortality due to osteoporosis-related fractures. Our earlier findings in rodent male and female models of osteoporosis, as well as postmenopausal women strongly suggest the efficacy of prunes (dried plum) in reducing inflammation and preventing/reversing bone loss. The objective of this study was to examine the effects of two doses of prunes, daily, on biomarkers of inflammation and bone metabolism in men with some degree of bone loss (BMD; t-score between -0.1 and -2.5 SD), for three months. Thirty-five men between the ages of 55 and 80 years were randomized into one of three groups: 100 g prunes, 50 g prunes, or control. Consumption of 100 g prunes led to a significant decrease in serum osteocalcin (p < 0.001). Consumption of 50 g prunes led to significant decreases in serum osteoprotegerin (OPG) (p = 0.003) and serum osteocalcin (p = 0.040), and an increase in the OPG:RANKL ratio (p = 0.041). Regular consumption of either 100 g or 50 g prunes for three months may positively affect bone turnover.

Feasibility of an MI-CBT ketogenic adherence program for older adults with mild cognitive impairment.

BACKGROUND: The National Institutes of Health Obesity-Related Behavioral Intervention Trials model for intervention development was used to establish the feasibility and proof of concept of a motivational ketogenic nutrition adherence program for older adults with mild cognitive impairment. METHODS: This was a single-arm, single-center feasibility trial. A comprehensive assessment protocol, including a clinical interview, neuropsychological testing, and genetic sequencing was used as an initial screening. Nine participants (aged 64-75) with possible amnestic mild cognitive impairment were consented for the intervention. Participants completed pre- and post-intervention neuropsychological assessments using the updated Repeatable Battery for Assessment of Neuropsychological Status. Participants tracked their macronutrient consumption using food diaries and ketone levels using urinalysis test strips daily. Mood and other psychosocial variables were collected through surveys, and qualitative exit interviews were completed. RESULTS: 100% of participants who began the trial completed the 6-week ketogenic nutrition adherence program, including completion of the pre- and post-assessments. Eight participants achieved measurable levels of ketones during the program. The average self-rated adherence across the program was 8.7 out of 10. A Wilcoxon Signed-Rank test demonstrated significant improvement in cognitive performance from baseline (median = 88) to follow up (median = 96, Z = - 2.26, p = .024). The average difference in cognitive performance from baseline to follow-up was - 7.33 (95% CI - 12.85, - 1.82). CONCLUSIONS: Results supported the feasibility for moving to the next phase and demonstrated proof of concept for the intervention. The next step is a randomized pilot trial to test clinical signals of effect compared to a control condition. TRIAL REGISTRATION: This trial was retrospectively registered with clinicaltrials.gov on July 13, 2021. The trial number is NCT04968041.

Effects of strawberries on bone biomarkers in pre- and stage 1-hypertensive postmenopausal women: a secondary analysis.

Postmenopausal women experience an increase in bone remodeling with the rate of bone resorption superseding the rate of bone formation. This results in a net bone loss with a subsequent increased risk for osteoporosis and fractures. High blood pressure (BP) has been associated with loss of bone mineral density and increased propensity to fractures. Strawberries are rich in polyphenols, which have been shown to have anti-hypertensive and bone-protective properties. Thus, we examined whether daily intake of strawberries would positively affect biomarkers of bone metabolism in postmenopausal women with pre- and stage 1-hypertension. Participants (age: 59 ± 6 years; body mass index: 31.5 ± 4.1 kg m-2; systolic BP: 140 ± 13 mmHg) were randomly assigned to consume (1) 50 g of freeze-dried strawberry powder (FDSP), (2) 25 g FDSP + 25 g of placebo powder, or (3) 50 g placebo powder for eight weeks. Results indicate a significant time-by-treatment interaction (P = 0.04) for serum insulin-like growth factor (IGF)-1, a hormone that plays a major role in bone formation. Serum concentrations of bone-specific alkaline phosphatase, a marker of bone formation, and tartrate-resistant acid phosphatase-5b, a specific marker of bone resorption, were not affected by FDSP compared to placebo. Although not statistically significant, after eight weeks, osteocalcin increased in the 50 g FDSP group with a large effect size (d = 0.6) when compared to the placebo-control group. Adiponectin increased by 5% and 6% in the 25 g and 50 g FDSP groups, respectively, while it declined in the placebo-control group by 25% (P = 0.03 for time-by-treatment interaction). Our findings suggest that consumption of 25 g FDSP increases IGF-1 in postmenopausal women with pre- and stage 1-hypertension. However, further studies are needed to assert the effectiveness of a strawberry intervention for bone health.

Cornus officinalis var. koreana Kitam polyphenol extract decreases pro-inflammatory markers in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages by reducing Akt phosphorylation.

ETHNOPHARMACOLOGICAL RELEVANCE: Cornus officinalis var. koreana Kitam (CO) is found predominantly in China but also in Korea and Japan and has been used in Eastern medicine for over 2000 years to treat several conditions including diabetes, cardiovascular disease and kidney disease. Chronic inflammation underlies the pathogenesis of these diseases. The mechanisms by which CO may exert its anti-inflammatory effects have not been well defined. AIM OF THE STUDY: We aimed to determine whether Cornus officinalis var. koreana Kitam extract (COE) attenuate the inflammatory response induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages, and to elucidate the mechanisms which contribute to these anti-inflammatory effects. MATERIALS AND METHODS: COE was prepared using ethanolic extraction, followed by solvent evaporation and freeze-drying. RAW 264.7 macrophages were treated with 0, 50, 100, 200 and 400 µg/ml of COE. After 2 h, cells were treated with 100 ng/ml of LPS for 6 h. Cells were then collected for whole cell protein expression analysis of signaling and inflammatory molecules via western blot. RESULTS: Pre-treatment with 100, 200 and 400 µg/ml of COE significantly reduced Akt phosphorylation in LPS stimulated macrophages compared to LPS alone (P ≤ 0.003). NF-κB expression was significantly attenuated with 400 µg/ml of COE compared to LPS treatment alone (P = 0.01). LPS induced cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) expression, which was significantly decreased by treatment with 400 µg/ml COE (P = 0.0001 and 0.02, respectively). COE dose-dependently decreased LPS-induced expression of interleukin (IL)-1ß (P ≤ 0.0008) and IL-6 (P = 0.01). CONCLUSION: In summary, COE attenuated the inflammatory response induced by LPS in RAW 264.7 macrophages, likely due to Akt inhibition.

Macrophage Polarization and Osteoporosis: A Review.

Over 200 million people suffer from osteoporosis worldwide. Individuals with osteoporosis have increased rates of bone resorption while simultaneously having impaired osteogenesis. Most current treatments for osteoporosis focus on anti-resorptive methods to prevent further bone loss. However, it is important to identify safe and cost-efficient treatments that not only inhibit bone resorption, but also stimulate anabolic mechanisms to upregulate osteogenesis. Recent data suggest that macrophage polarization may contribute to osteoblast differentiation and increased osteogenesis as well as bone mineralization. Macrophages exist in two major polarization states, classically activated macrophages (M1) and alternatively activated macrophage (M2) macrophages. The polarization state of macrophages is dependent on molecules in the microenvironment including several cytokines and chemokines. Mechanistically, M2 macrophages secrete osteogenic factors that stimulate the differentiation and activation of pre-osteoblastic cells, such as mesenchymal stem cells (MSC's), and subsequently increase bone mineralization. In this review, we cover the mechanisms by which M2 macrophages contribute to osteogenesis and postulate the hypothesis that regulating macrophage polarization states may be a potential treatment for the treatment of osteoporosis.

The Relationship between Protein Intake and Source on Factors Associated with Glycemic Control in Individuals with Prediabetes and Type 2 Diabetes.

Type 2 diabetes (T2D) is a major contributor to morbidity and mortality largely due to increased cardiovascular disease risk. This study examined the relationships among protein consumption and sources on glycemic control and cardiovascular health in individuals with prediabetes and T2D. Sixty-two overweight or obese participants with prediabetes or T2D, aged 45-75 years were stratified into the following three groups based on protein intake: <0.8 g (gram)/kg (kilogram) body weight (bw), ≥0.8 but <1.0 g/kg bw, and ≥1.0 g/kg bw as below, meeting, and above the recommended levels of protein intake, respectively. Body mass, body mass index (BMI), hip circumference (HC), waist circumference (WC), lean mass, and fat mass (FM) were significantly higher in participants who consumed below the recommended level of protein intake as compared with other groups. Higher animal protein intake was associated with greater insulin secretion and lower triglycerides (TG). Total, low-density, and high-density cholesterol were significantly higher in participants who met the recommended protein intake as compared with the other groups. These data suggest that high protein consumption is associated with lower BMI, HC, WC, and FM, and can improve insulin resistance without affecting lipid profiles in this population. Furthermore, higher intake of animal protein can improve ß-cell function and lower plasma TG.

Effects of Montmorency Tart Cherry Juice Consumption on Cardiometabolic Biomarkers in Adults with Metabolic Syndrome: A Randomized Controlled Pilot Trial.

Greater than one-third of adults in the United States have metabolic syndrome (MetS), a cluster of risk factors highly associated with the development of cardiovascular diseases. Premature vascular dysfunction in MetS may lead to accelerated age-related atherogenesis and arterial stiffening, thereby increasing cardiovascular risk. Montmorency tart cherries (Prunus cerasus L.) are rich in bioactive compounds, such as anthocyanins, known to exert cardiovascular protective effects. Previous research suggests that tart cherry juice consumption may improve cardiovascular health. The objective of this study was to evaluate the effects of daily consumption of tart cherry juice on hemodynamics, arterial stiffness, and blood biomarkers of cardiovascular and metabolic health in men and women with MetS. In a randomized, single-blind, placebo-controlled, parallel-arm pilot clinical trial, 19 men and women 20 to 60 years of age with MetS consumed 240 mL of tart cherry juice (Tart Cherry; n = 5 males, 4 females) or an isocaloric placebo-control drink (Control; n = 5 males, 5 females) twice daily for 12 weeks. Arterial stiffness (pulse wave velocity), brachial and aortic blood pressures, wave reflection (augmentation index), and blood biomarkers of cardiovascular and metabolic health were assessed at baseline and 6 and 12 weeks. Oxidized low-density lipoprotein and soluble vascular cell adhesion molecule-1 were significantly lower (P = .047 and P = .036, respectively) in Tart Cherry than Control at 12 weeks, but were not significantly lower than baseline values. There was a trend for total cholesterol to be lower (P = .08) in Tart Cherry than Control at 12 weeks. No significant changes were observed in hemodynamics, arterial stiffness, or other blood biomarkers assessed. These results suggest that daily tart cherry consumption may attenuate processes involved in accelerated atherogenesis without affecting hemodynamics or arterial stiffness parameters in this population. The pilot nature of this study warrants interpreting these findings with caution, and future clinical trials with a larger sample size are needed to confirm these findings.

Gender differences in the effect of blackberry supplementation in vascular senescence and atherosclerosis in ApoE-/- mice.

As the cardiovascular system ages, it becomes more vulnerable to the effects of oxidative stress and inflammation. The aging process, along with external factors such as radiation exposure and lifestyle, induces vascular senescence and accelerates atherosclerotic plaque accumulation. Expression of nicotinamide adenine dinucleotide phosphate oxidase 1 (Nox1), which produces superoxide, is associated with senescence in vascular smooth muscle cells in vitro and atherosclerosis in ApoE-/- mice in vivo. However, it is unknown whether Nox1 could be down-regulated by nutritional interventions aimed to reduce atherosclerosis. Here we study the effect of blackberry supplementation in Nox1 expression and atherosclerosis. Four-month-old ApoE-/- male and female mice were fed low-fat, high-fat or high-fat supplemented with 2% freeze-dried blackberry powder diets for 5 weeks. Analysis of the aorta showed that diet supplemented with blackberry significantly decreased plaque accumulation, senescence associated-ß-galactosidase and Nox1 expression in the aorta of male but not female mice. The lipid profile was unchanged by blackberry in both female and male animals. Thus, the known role of Nox1 in atherosclerosis suggests that the atheroprotective effect of blackberry is mediated by Nox1 down-regulation in male mice and that Nox1 is regulated in a gender-dependent manner in females.

Is soy protein effective in reducing cholesterol and improving bone health?

Hyperlipidemia associated with cardiovascular health, and bone loss with regard to osteoporosis contribute to increased morbidity and mortality and are influenced by diet. Soy protein has been shown to reduce cholesterol levels, and its isoflavones may improve bone health. The objective of this study was to determine the effects of soy protein on lipid profiles and biomarkers of bone metabolism and inflammation. Ninety men and women (aged 27-87) were randomly assigned to consume 40 g of soy or casein protein daily for three months. Both soy and casein consumption significantly reduced bone alkaline phosphatase (P = 0.011) and body fat % (P < 0.001), tended to decrease tartrate-resistant acid phosphatase (P = 0.066), and significantly increased serum insulin-like growth factor-I (IGF-1) (P < 0.001), yet soy increased IGF-1 to a greater extent (P = 0.01) than casein. Neither treatment affected total cholesterol, HDL cholesterol, LDL cholesterol, or C-reactive protein. These results demonstrate that daily supplementation of soy and casein protein may have positive effects on indices of bone metabolism and body composition, with soy protein being more effective at increasing IGF-1, an anabolic factor, which may be due to soy isoflavones' role in upregulating Runx2 gene expression, while having little effect on lipid profiles and markers of inflammation.

Influence of daily fresh pear consumption on biomarkers of cardiometabolic health in middle-aged/older adults with metabolic syndrome: a randomized controlled trial.

Previous research suggests potential for fresh pears as a functional food for promoting cardiometabolic health. The purpose of this randomized, open-label, placebo-controlled, crossover clinical trial was to evaluate the influence of daily fresh pear consumption on blood pressure (primary outcome) and other biomarkers of cardiometabolic health in middle-aged/older adults with metabolic syndrome (MetS). Forty men and women aged 45-65 years with MetS were included and randomly assigned to receive either two medium-sized fresh pears (Pear) or a calorie-matched control drink (Control) per day for each 12-week treatment period, each separated by a 4-week washout period. After 12 weeks of daily fresh pear consumption, systolic blood pressure tended to be reduced (130 ± 2 mmHg vs. 134 ± 2 mmHg at baseline, P = 0.07) and pulse pressure was significantly reduced (51 ± 1 vs. 54 ± 1 at baseline, P < 0.05). At 12 weeks, leptin concentrations were lower in the Pear group than Control (52.5 [7.6, 120.5] ng dL-1vs. 53.4 [5.0, 120.5] ng dL-1, respectively, P < 0.05), and there was a significant group by time interaction (P < 0.05). Leptin concentrations were significantly reduced at 12 weeks compared to baseline in the Pear group (52.5 [7.6, 120.5] ng dL-1vs. 54.8 [6.4, 120.5] ng dL-1 at baseline, P < 0.05) but not in the Control group. Waist circumference was significantly reduced at 12 weeks in the Pear group (107.7 ± 2.0 cm vs. 108.4 ± 2 cm at baseline, P < 0.05) with a trend for a group by time interaction (P < 0.1), and significantly lower in the Pear group than Control (108.1 ± 2.0 cm vs. 108.8 ± 2 cm, P < 0.05) at 6 weeks with a significant group by time interaction (P < 0.05). Conversely, values were significantly increased at 6 weeks (108.8 ± 2 cm vs. 108.3 ± 2.0 cm at baseline, P < 0.05) in the Control group and sustained at 12 weeks. Waist-to-hip ratio was significantly reduced (0.92 ± 0.01 vs. 0.93 ± 0.01 at baseline, P < 0.05) at 12 weeks in the Pear group, and significantly lower than Control at 6 weeks (0.93 ± 0.01 vs. 0.93 ± 0.01, respectively, P < 0.05) and 12 weeks (0.92 ± 0.01 vs. 0.93 ± 0.01, P < 0.05). These findings suggest that daily fresh pear consumption may promote modest improvements in cardiometabolic health in middle-aged/older adults with MetS. This trial was registered at clinicaltrials.gov as NCT02228837.

Egg consumption may improve factors associated with glycemic control and insulin sensitivity in adults with pre- and type II diabetes.

Without appropriate interventions, prediabetes is typically followed by type II diabetes. Eggs are a rich source of important nutrients including protein, vitamins, minerals, carotenoids and lecithin. In this 12-week, parallel, randomized controlled trial, 42 overweight or obese individuals between the ages of 40 and 75 years with pre- and type II-diabetes were included. Participants were randomly assigned to receive either one large egg per day or an equivalent amount of egg substitute for 12 weeks. Blood samples were obtained to analyze lipid profile and biomarkers associated with glycemic control at all time points. Regular egg consumption resulted in improvements of fasting blood glucose, which was significantly (P = 0.05) reduced by 4.4% at the final visit in the egg group. Participants in the egg group had significantly (P = 0.01) lower levels of homeostatic model assessment of insulin resistance (HOMA-IR) at all visits. In the egg group, ATP-binding cassette protein family A1 (ABCA1) was significantly higher at the 6-week visit (0.78 ± 0.21 vs. 0.28 ± 0.05 mg dL-1, P < 0.001) and tended to be higher at the final visit (0.62 ± 0.11 vs. 0.55 ± 0.18 mg dL-1, P = 0.1). The mean apolipoprotein A1 (apo A1) level was also significantly higher at the final visit in the egg group compared to the control (147.43 ± 5.34 vs. 142.81 ± 5.09 mg dL-1, P = 0.01). There were no significant changes in total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels. Daily consumption of one large egg may reduce the risk of diabetes without having any adverse effects on lipid profiles in individuals with pre- and type II diabetes.

Functionality in Middle-Aged and Older Overweight and Obese Individuals with Knee Osteoarthritis.

Patients with knee osteoarthritis (OA) suffer from immobility and pain. The objective of this cross-sectional study was to investigate the relationship between pain and functionality in middle-aged and older overweight and obese individuals with mild-to-moderate knee OA. Overall pattern, physical activity, and total energy expenditure (TEE) were assessed in 83 participants. The Western Ontario McMaster Universities Arthritis Index (WOMAC) was used to assess lower extremity pain and function. The six-minute walk test (6-MWT) and range of motion (ROM) were also assessed. Results indicated that age was inversely associated with body mass index (BMI) (r = 0.349) and total WOMAC scores (r = 0.247). BMI was positively associated with TEE (r = 0.430) and WOMAC scores (r = 0.268), while ROM was positively associated with the 6-MWT (r = 0.561) and negatively associated with WOMAC (r = 0.338) and pain scores (r = 0.222). Furthermore, women had significantly greater WOMAC scores (p = 0.046) than men. Older participants (≥65 years old) had significantly lower BMI (p = 0.002), and distance traveled during the 6-MWT (p = 0.013). Our findings indicate that older individuals in this population with knee OA had lower BMI, greater ROM, and less pain and stiffness and walked slower than middle-aged individuals. Women reported greater pain, stiffness, and reduced functionality, indicating that the manifestation of OA may vary due to gender.

Gain-of-function mutations in beet DODA2 identify key residues for betalain pigment evolution.

The key enzymatic step in betalain biosynthesis involves conversion of l-3,4-dihydroxyphenylalanine (l-DOPA) to betalamic acid. One class of enzymes capable of this is 3,4-dihydroxyphenylalanine 4,5-dioxygenase (DODA). In betalain-producing species, multiple paralogs of this gene are maintained. This study demonstrates which paralogs function in the betalain pathway and determines the residue changes required to evolve a betalain-nonfunctional DODA into a betalain-functional DODA. Functionalities of two pairs of DODAs were tested by expression in beets, Arabidopsis and yeast, and gene silencing was performed by virus-induced gene silencing. Site-directed mutagenesis identified amino acid residues essential for betalamic acid production. Beta vulgaris and Mirabilis jalapa both possess a DODA1 lineage that functions in the betalain pathway and at least one other lineage, DODA2, that does not. Site-directed mutagenesis resulted in betalain biosynthesis by a previously nonfunctional DODA, revealing key residues required for evolution of the betalain pathway. Divergent functionality of DODA paralogs, one clade involved in betalain biosynthesis but others not, is present in various Caryophyllales species. A minimum of seven amino acid residue changes conferred betalain enzymatic activity to a betalain-nonfunctional DODA paralog, providing insight into the evolution of the betalain pigment pathway in plants.

Impact of daily strawberry consumption on blood pressure and arterial stiffness in pre- and stage 1-hypertensive postmenopausal women: a randomized controlled trial.

Growing evidence indicates that strawberries are cardioprotective. We conducted an eight-week randomized, double-blind, placebo-controlled, parallel arm clinical trial to investigate the effects of daily consumption of freeze-dried strawberry powder (FDSP) on blood pressure (BP) and arterial stiffness in pre- and stage 1-hypertensive postmenopausal women. Sixty postmenopausal women were randomly assigned to one of three groups: (1) control, (2) 25 g FDSP and (3) 50 g FDSP (n = 20 per group). Assessments of body weight, BP, arterial stiffness as measured by pulse wave velocity (PWV), and collection of blood samples for analyses of vasoactive and antioxidant molecules were performed at baseline, four and eight weeks. After eight weeks, systolic BP, as well as brachial- and femoral-ankle PWV were lower than baseline in the 25 g FDSP group (141 ± 3 to 135 ± 3 mmHg, P = 0.02; 15.5 ± 0.5 to 14.8 ± 0.4 m s-1, P = 0.03, and 11.0 ± 0.2 to 10.4 ± 0.2 m s-1, P = 0.02, respectively), whereas no statistically significant changes were observed in the control or 50 g FDSP groups. Plasma nitric oxide metabolite levels increased at four and eight weeks in the 50 g FDSP group compared to baseline (8.5 ± 1.2 to 13.6 ± 1.3 and 13.3 ± 1.5, respectively, P = 0.01), whereas no significant changes were observed in the control or 25 g FDSP groups. Serum levels of superoxide dismutase increased at four weeks returning to baseline levels at eight weeks in all three groups. Significant differences among groups were not detected for any of the parameters. Although BP and arterial stiffness improved in the 25 g FDSP group over time, a treatment effect was not observed. Thus, it would be premature to affirm that daily consumption of FDSP improves BP or vascular function in pre- and stage 1-hypertensive postmenopausal women. This trial was registered at as NCT02099578.

Bone-Protective Effects of Dried Plum in Postmenopausal Women: Efficacy and Possible Mechanisms.

Osteoporosis is an age-related chronic disease characterized by a loss of bone mass and quality, and is associated with an increased risk of fragility fractures. Postmenopausal women are at the greatest risk of developing osteoporosis due to the cessation in ovarian hormone production, which causes accelerated bone loss. As the demographic shifts to a more aged population, a growing number of postmenopausal women will be afflicted with osteoporosis. Certain lifestyle factors, including nutrition and exercise, are known to reduce the risk of developing osteoporosis and therefore play an important role in bone health. In terms of nutrition, accumulating evidence suggests that dried plum (Prunus domestica L.) is potentially an efficacious intervention for preventing and reversing bone mass and structural loss in an ovariectomized rat model of osteoporosis, as well as in osteopenic postmenopausal women. Here, we provide evidence supporting the efficacy of dried plum in preventing and reversing bone loss associated with ovarian hormone deficiency in rodent models and in humans. We end with the results of a recent follow-up study demonstrating that postmenopausal women who previously consumed 100 g dried plum per day during our one-year clinical trial conducted five years earlier retained bone mineral density to a greater extent than those receiving a comparative control. Additionally, we highlight the possible mechanisms of action by which bioactive compounds in dried plum exert bone-protective effects. Overall, the findings of our studies and others strongly suggest that dried plum in its whole form is a promising and efficacious functional food therapy for preventing bone loss in postmenopausal women, with the potential for long-lasting bone-protective effects.

Effects of daily blueberry consumption on circulating biomarkers of oxidative stress, inflammation, and antioxidant defense in postmenopausal women with pre- and stage 1-hypertension: a randomized controlled trial.

Oxidative stress and inflammation are central to the development of a number of chronic diseases including cardiovascular disease and previous research suggests that blueberry consumption may attenuate these processes. The present study investigated the effects of blueberries on blood biomarkers of oxidative stress, inflammation, and antioxidant defense in postmenopausal women with pre- and stage 1-hypertension. In a randomized, parallel-arm, double-blind, placebo-controlled clinical trial, 40 pre- and stage 1-hypertensive postmenopausal women aged 45 to 65 years were randomly assigned to receive 22 g freeze-dried highbush blueberry powder per day (Blueberry) or 22 g placebo powder per day (Control) for 8 weeks. A blood biomarker of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine (8-OHdG), as well as blood biomarkers of oxidative stress, inflammation, and antioxidant defense were assessed at baseline, 4 and 8 weeks. 8-OHdG levels were significantly (P = 0.008) lower in Blueberry compared to Control at 4 weeks with a significant time-by-treatment interaction (P = 0.04). Levels were not different between groups at 8 weeks. Other biomarkers measured were not affected by blueberry consumption. Daily consumption of blueberries for 4 weeks, but not 8 weeks, attenuated a biomarker of oxidative DNA damage in pre- and stage 1-hypertensive postmenopausal women. Future clinical studies should directly evaluate the effects of blueberry consumption on oxidative stress, inflammation, and antioxidant defense at the cellular level and in the vasculature in this population.

TTG2 controls the developmental regulation of seed coat tannins in Arabidopsis by regulating vacuolar transport steps in the proanthocyanidin pathway.

The brown color of Arabidopsis seeds is caused by the deposition of proanthocyanidins (PAs or condensed tannins) in their inner testa layer. A transcription factor complex consisting of TT2, TT8 and TTG1 controls expression of PA biosynthetic genes, just as similar TTG1-dependent complexes have been shown to control flavonoid pigment pathway gene expression in general. However, PA synthesis is controlled by at least one other gene. TTG2 mutants lack the pigmentation found in wild-type seeds, but produce other flavonoid compounds, such as anthocyanins in the shoot, suggesting that TTG2 regulates genes in the PA biosynthetic branch of the flavonoid pathway. We analyzed the expression of PA biosynthetic genes within the developing seeds of ttg2-1 and wild-type plants for potential TTG2 regulatory targets. We found that expression of TT12, encoding a MATE type transporter, is dependent on TTG2 and that TTG2 can bind to the upstream regulatory region of TT12 suggesting that TTG2 directly regulates TT12. Ectopic expression of TT12 in ttg2-1 plants partially restores seed coat pigmentation. Moreover, we show that TTG2 regulation of TT12 is dependent on TTG1 and that TTG1 and TTG2 physically interact. The observation that TTG1 interacts with TTG2, a WRKY type transcription factor, proposes the existence of a novel TTG1-containing complex, and an addendum to the existing paradigm of flavonoid pathway regulation.

Tyrosine Hydroxylation in Betalain Pigment Biosynthesis Is Performed by Cytochrome P450 Enzymes in Beets (Beta vulgaris).

Yellow and red-violet betalain plant pigments are restricted to several families in the order Caryophyllales, where betacyanins play analogous biological roles to anthocyanins. The initial step in betalain biosynthesis is the hydroxylation of tyrosine to form L-DOPA. Using gene expression experiments in beets, yeast, and Arabidopsis, along with HPLC/MS analysis, the present study shows that two novel cytochrome P450 (CYP450) enzymes, CYP76AD6 and CYP76AD5, and the previously described CYP76AD1 can perform this initial step. Co-expressing these CYP450s with DOPA 4,5-dioxygenase in yeast, and overexpression of these CYP450s in yellow beets show that CYP76AD1 efficiently uses L-DOPA leading to red betacyanins while CYP76AD6 and CYP76AD5 lack this activity. Furthermore, CYP76AD1 can complement yellow beetroots to red while CYP76AD6 and CYP76AD5 cannot. Therefore CYP76AD1 uniquely performs the beet R locus function and beets appear to be genetically redundant for tyrosine hydroxylation. These new functional data and ancestral character state reconstructions indicate that tyrosine hydroxylation alone was the most likely ancestral function of the CYP76AD alpha and beta groups and the ability to convert L-DOPA to cyclo-DOPA evolved later in the alpha group.