Omega-3 Supplementation for the Prevention of Cognitive Decline in Older Adults: Does It Depend on Homocysteine Levels?

BACKGROUND: Recent evidence point towards an interaction between omega-3 (n-3) polyunsaturated fatty acids (PUFA) and plasma homocysteine (Hcy). OBJECTIVES: This study tested the hypothesis that effects of red blood cell n-3 PUFA are modified according to baseline plasma Hcy in the large Mulit-domain Alzheimer Prevention Trial (MAPT) throughout the 3-years of treatment with an additional 2 years of observational follow-up. DESIGN: Experimental study. PARTICIPANTS: From the 1680 participants that were randomized in the four groups of the MAPT study (two of which received n-3 PUFA, the other two without n-3 PUFA), 782 were selected because they had baseline data on both Hcy and n-3 PUFA. MEASUREMENTS: Cognitive performance was measured with a broad set of cognitive tests including free and total recall of the cued selective reminding test, digit symbol substitution test, category naming test and Trail-making tests (TMT-A and B) and Clinical dementia rating scale. RESULTS: We found a significant association between TMT-A and red blood cell n-3 PUFA levels in participants with Hcy values ≤16.8 µMol/L after adjustments at baseline (Estimate: -1.3, 95% CI: -2.3; -0.3, p=0.01). Additionally, participants with high Hcy values had a significant worsening after adjustments in TMT-B after a 5-year n-3 PUFA supplementation, compared to low levels of Hcy (Mean difference: 34.8, 95% CI: 7.8;61.7). CONCLUSION: This study shows that Hcy levels could modify the association between red blood cell n-3 PUFA and executive function. People with high Hcy may benefit less from a n-3 PUFA supplementation to prevent cognitive decline.

Effects of trace mineral amount and source on aspects of oxidative metabolism and responses to intramammary lipopolysaccharide challenge in midlactation dairy cows.

Trace minerals have important roles in immune function and oxidative metabolism; however, little is known about the relationships between supplementation level and source with outcomes in dairy cattle. Multiparous Holstein cows (n=48) beginning at 60 to 140 days in milk were utilized to determine the effects of trace mineral amount and source on aspects of oxidative metabolism and responses to intramammary lipopolysaccharide (LPS) challenge. Cows were fed a basal diet meeting National Research Council (NRC) requirements except for no added zinc (Zn), copper (Cu) or manganese (Mn). After a 4-week preliminary period, cows were assigned to one of four topdress treatments in a randomized complete block design with a 2×2 factorial arrangement of treatments: (1) NRC inorganic (NRC levels using inorganic (sulfate-based) trace mineral supplements only); (2) NRC organic (NRC levels using organic trace mineral supplements (metals chelated to 2-hydroxy-4-(methythio)-butanoic acid); (3) commercial inorganic (approximately 2×NRC levels using inorganic trace mineral supplements only; and (4) commercial organic (commercial levels using organic trace mineral supplements only). Cows were fed the respective mineral treatments for 6 weeks. Treatment effects were level, source and their interaction. Activities of super oxide dismutase and glutathione peroxidase in erythrocyte lysate and concentrations of thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) in plasma were measured as indices of oxidative metabolism. Effects of treatment on those indices were not significant when evaluated across the entire experimental period. Plasma immunoglobulin G level was higher in cows supplemented with organic trace minerals over the entire treatment period; responses assessed as differences of before and after Escherichia coli J5 bacterin vaccination at the end of week 2 of treatment period were not significant. Cows were administered an intramammary LPS challenge during week 5; during week 6 cows fed commercial levels of Zn, Cu and Mn tended to have higher plasma TAC and cows fed organic sources had decreased plasma TBARS. After the LPS challenge, the extent and pattern of response of plasma cortisol concentrations and clinical indices (rectal temperature and heart rate) were not affected by trace mineral level and source. Productive performance including dry matter intake and milk yield and composition were not affected by treatment. Overall, results suggest that the varying level and source of dietary trace minerals do not have significant short-term effects on oxidative metabolism indices and clinical responses to intramammary LPS challenge in midlactation cows.

Cross-Sectional Associations of Total Plasma Homocysteine with Cortical ß-Amyloid Independently and as a Function of Omega 3 Polyunsaturated Fatty Acid Status in Older Adults at Risk of Dementia.

OBJECTIVES: Elevated total plasma homocysteine is a risk factor for Alzheimer's disease (AD) and there is some evidence that omega-3 polyunsaturated fatty acids (n-3 PUFAs) can modulate the effects of homocysteine-lowering B vitamins on AD related pathologies. Hence we investigated the relationship between total plasma homocysteine and cortical ß-amyloid (Aß) in older adults at risk of dementia. The role of erythrocyte membrane n-3 PUFAs (omega 3 index) on this relationship was also explored. DESIGN: This is a cross-sectional study using data from the Multidomain Alzheimer Preventive Trial (MAPT); a randomised controlled trial. SETTING: French community dwellers aged 70 or over reporting subjective memory complaints, but free from a diagnosis of clinical dementia. PARTICIPANTS: Individuals were from the MAPT trial (n = 177) with data on total plasma homocysteine at baseline and cortical Aß load. MEASUREMENTS: Cortical-to-cerebellar standard uptake value ratios were assessed using [18F] florbetapir positron emission tomography (PET). Total baseline plasma homocysteine was measured using an enzymatic cycling assay. Baseline omega 3 index was measured using gas chromatography. Cross-sectional associations were explored using adjusted multiple linear regression models. RESULTS: We found that total baseline plasma homocysteine was not significantly associated with cortical Aß as demonstrated using multiple linear regression models adjusted for age, sex, education, cognitive status, time interval between baseline and PET-scan, omega-3 index, MAPT group allocation and Apolipoprotein E ε4 status (B-coefficient -0.001, 95 % CI: -0.008,0.006, p = 0.838). Exploratory analysis showed that homocysteine was however significantly associated with cortical Aß in subjects with low baseline omega-3 index (< 4.72 %) after adjustment for Apolipoprotein E ε4 status (B-coefficient 0.041, 95 % CI: 0.017,0.066, p = 0.005, n = 10), but not in subjects with a high baseline omega-3 index (B-coefficient -0.010, 95 % CI: -0.023,0.003, p = 0.132, n = 66). CONCLUSIONS: The role of n-3 PUFAs on the relationship between homocysteine and cerebral Aß warrants further investigation.

Meta-analysis of lactation performance in dairy cows receiving supplemental dietary methionine sources or postruminal infusion of methionine.

The objectives of our study were to evaluate the productive response to methionine supplementation in lactating dairy cows and to define a relationship between metabolizable Met (MP Met) intake and production. A database of 64 papers meeting the selection criteria was developed evaluating postruminally infused dl-methionine (9 papers with 18 control diets and 35 treatment comparisons), 2-hydroxy-4-methylthio butanoic acid (HMTBa) provided as either a liquid or Ca salt form (17 papers with 34 control diets and 46 treatment comparisons), Mepron (Evonik Industries, Essen, Germany; 18 papers with 35 control diets and 42 treatment comparisons), and Smartamine (Adisseo Inc., Antony, France; 20 papers with 30 control diets and 39 treatment comparisons). Dietary ingredients and their accompanying nutritional compositions as described in the reports were entered into the Cornell-Penn-Miner software to model the diets and to predict nutrients that were not reported in the original publication. Data were analyzed using a weighted analysis of response to supplementation compared with the intraexperiment control, as well as through a regression analysis to changing dietary MP Met. Data included in the analysis were from experiments published between 1970 and 2011 with cows supplemented with between 3.5 and 67.9 g of Met or its equivalent from HMTBa. Cows supplemented with Smartamine consumed more, whereas cows supplemented with Mepron consumed less DM compared with controls. Milk yield did not significantly respond to Met supplementation, although it tended to increase for cows supplemented with HMTBa and Mepron. Milk protein yield was increased due to supplementation from all sources or from infusion, and protein concentration was greater for all supplements or infusion of dl-Met, except for cows supplemented with HMTBa. Irrespective of Met source, milk protein yield increased 2.23 g of protein/g of MP Met until reaching the breakpoint. Milk fat yield was increased for Mepron and HMTBa, whereas milk fat concentration was increased for infused dl-Met and for cows supplemented with HMTBa. Based on regression analysis, response of milk fat yield to Met supplementation was not different for infused dl-Met, Mepron, and Smartamine (1.87 g of fat/g of MP Met), whereas the response to HMTBa was significantly greater at 5.38 g of fat/g of MP Met.

Serum vitamin D concentrations are associated with falling and cognitive function in older adults.

OBJECTIVES: To elucidate the mechanism through which vitamin D is associated with decreased falls. DESIGN: This was a convenience sample from a larger observational study examining correlations between vitamin D and 1) falls, 2) motor function, and 3) cognition (n=159). SETTING: Falls data were collected via weekly on-line surveys completed in the participants' homes. Yearly evaluations of motor and cognitive function were conducted in an out-patient setting of a large tertiary medical center. PARTICIPANTS: Participants from the Intelligent Systems for Assessment of Aging Changes Study (ISAAC), a community-based cohort study of independently living older adults over age 70, who had vitamin D concentration within 6 months of clinical evaluations were included in the analysis. RESULTS: Participants mean age was 85 years and 74% were women. Fallers (n=37) had significantly lower vitamin D concentration (32.9ng/ml) compared to non-fallers (39.2ng/ml) (p<0.01). The relationship between vitamin D and falls remained significant after adjusting for age, health status (via CIRS), and supplement use (p=0.004). Vitamin D concentration were significantly associated with cognitive impairment (Clinical Dementia Rating = 0.5) (p=0.02) and MMSE (p<0.01) after adjusting for age, gender, and education. Vitamin D concentrations did not correlate with any motor measures. CONCLUSION: Vitamin D concentrations correlated with cognition and falls, but not with motor measures. Further research is needed to demonstrate a causal relationship between vitamin D and cognitive function and determine if cognition plays a role in falls reduction.

Effects of feeding a dietary antioxidant in diets with oxidized fat on lactation performance and antioxidant status of the cow.

The objective of the study was to evaluate the effect of feeding the dietary antioxidant Agrado Plus (AOX; Novus International, St. Louis, MO) in diets that contained 2% fresh fat (FF) or oxidized fat (OF) on milk production and composition and antioxidant status of cows during mid to late lactation. Forty-four mid to late lactating primiparous cows housed in a tie-stall barn were fed a diet that contained 2% FF for 15 d as adaptation period and then randomly allocated to 1 of the 4 dietary treatments (FF, FF+AOX, OF, OF +AOX) for 6 wk. Feeding AOX increased dry matter intake, 3.5% fat-corrected milk, and milk fat yield, and decreased milk protein content but not yield. Feeding OF increased milk fat yield, but decreased dry matter intake and body weight gain. Milk fat composition changed with treatments: AOX increased cis 18:1 and decreased trans-11 18:1, whereas OF decreased trans-9 and trans-11 18:1 and cis-9, trans-11 18:2 in milk. Plasma antioxidant enzymes and status were affected by treatments. Feeding OF increased superoxidase dismutase activity but decreased plasma antioxidant status, whereas AOX supplementation increased glutathione peroxidase activity across fat types and increased the antioxidant status and superoxidase dismutase activity when feeding OF diets. It can be concluded that feeding AOX improved lactation performance and the antioxidant status of the cow across fat types, and feeding OF increased milk fat yield but decreased dry matter intake, body weight gain, and antioxidant status. The negative effects of feeding OF were partially alleviated by AOX.

The proportion of the diet to which fibrolytic enzymes are added affects nutrient digestion by lactating dairy cows.

Eight lactating Holstein cows, four with ruminal cannulas, were used in a duplicated 4 x 4 Latin square design to investigate a fibrolytic enzyme product characterized by xylanase and cellulase activities (Promote N.E.T. Agribrands International, St. Louis, MO). The diet consisted of concentrate containing rolled barley and supplement, barley silage and alfalfa haylage (55% to 45% DM basis, forage to concentrate ratio) and differed in enzyme application: 1) control, 2) enzyme applied to concentrate (45% of TMR), 3) enzyme applied to supplement (4% of TMR), and 4) enzyme applied to premix (0.2% of TMR). All diets that were supplemented with the enzyme product delivered about 1.0 grams per cow per day. Digestibility of OM, NDF and ADF in the total tract was increased in comparison to the control when enzymes were added to the entire concentrate. Enzyme treatments that were applied to a smaller portion of the diet showed only numerical increases in digestibility over the control. However, there was an increase in microbial N synthesis for cows fed enzymes added to the premix. The effects of enzyme supplementation on milk production and composition were not statistically significant, but cows receiving the enzyme product added to the concentrate had a numerically higher FCM compared to the control cows. These results indicate that enzyme supplementation increases total tract digestibility of organic matter and fiber. The proportion of the diet to which the enzyme is applied must be maximized to ensure a beneficial response.