α-Linolenic acid, linoleic acid and heart failure in women

α-Linolenic acid (18?:?3n-3) intake and linoleic acid (18?:?2n-6) intake have been associated with lower rates of CHD, though results have not been consistent. The relationship of these fatty acids with incident heart failure (HF) is not well established. We examined the hypothesis that women with higher intakes of 18?:?3n-3 and 18?:?2n-6 would have lower rates of HF hospitalisation and mortality. We measured 18?:?3n-3 and 18?:?2n-6 intake in 36?234 Swedish Mammography Cohort participants aged 48-83 years using FFQ and followed participants through Swedish inpatient and cause-of-death registers from 1 January 1998 until 31 December 2006. Cox models were used to calculate incidence rate ratios (RR) and 95?% CI. Because of multicollinearity, 18?:?3n-3 and 18?:?2n-6 were examined separately. Over 9 years, 596 women were hospitalised and fifty-five died due to HF. In models accounting for age and other covariates, the RR for HF comparing the top quintile of 18?:?3n-3 (median 1·50?g/d) with the bottom quintile (median 0·88?g/d) was 0·91 (95?% CI 0·71, 1·17, P trend?=?0·41). The RR comparing the top quintile of 18?:?2n-6 (median 7·8?g/d) with the bottom quintile (median 4·6?g/d) was 1·14 (95?% CI 0·88, 1·46, P trend?=?0·36). We did not find evidence for the interaction of 18?:?3n-3 and 18?:?2n-6 with each other or with long-chain n-3 fatty acids. In conclusion, these data do not support our hypothesis that 18?:?3n-3 and 18?:?2n-6 are associated with HF. However, these results may not be generalisable to populations with higher intakes of 18?:?3n-3.     

High levels of stearic acid,palmitoleic acid,and dihomo-γ-linolenic acid and low levels of linoleic acid in serum cholesterol ester are associated with high insulin resistance

The association of fatty acid composition with insulin resistance and type 2 diabetes has been reported in Western populations, but there is limited evidence of this association among the Japanese, whose populace consume large amounts of fish. To test the hypothesis that high palmitic, palmitoleic, and dihomo-γ-linolenic acids and low levels of linoleic and n-3 fatty acids are associated with higher insulin resistance among the Japanese, the authors investigated the relationship between serum fatty acid composition and serum C-peptide concentrations in 437 Japanese employees aged 21 to 67 years who participated in a workplace health examination. Serum cholesterol ester and phospholipid fatty acid compositions were measured by gas-liquid chromatography. Desaturase activity was estimated by fatty acid product-to-precursor ratios. A multiple regression was used to assess the association between fatty acid and C-peptide concentrations. C-peptide concentrations were associated inversely with linoleic acid levels in cholesterol ester and phospholipid (P for trend = .01 and .02, respectively) and positively with stearic and palmitoleic acids in cholesterol ester (P for trend =.02 and .006, respectively) and dihomo-γ-linolenic acid in cholesterol ester and phospholipid (P for trend < .0001 for both). C-peptide concentrations were not associated with n-3 polyunsaturated fatty acids. C-peptide concentrations significantly increased as δ-9-desaturase (16:1 n-7/16:0) and δ-6-desaturase (18:3 n-6/18:2 n-6) increased (P for trend = .01 and .03, respectively) and δ-5-desaturase (20:4 n-6/20:3 n-6) decreased (P for trend = .004). In conclusion, a fatty acid pattern with high levels of serum stearic, palmitoleic, or dihomo-γ-linolenic acids; δ-9-desaturase (16:1 n-7/16:0) or δ-6-desaturase (18:3 n-6/18:2 n-6) activities; and low levels of serum linoleic acid or δ-5-desaturase (20:4 n-6/20:3 n-6) activity might be associated with higher insulin resistance in Japanese adults.     

Conjugated linoleic acid improves glucose utilization in the soleus muscle of rats fed linoleic acid–enriched and linoleic acid–deprived diets

The effect that conjugated linoleic acid (CLA) has on glucose metabolism in experimental animals depends on nutritional conditions. Therefore, we hypothesized that CLA improves glucose utilization and insulin sensitivity in rats fed different levels of dietary linoleic acid (LA). We investigated the effect of CLA on the uptake, incorporation, and oxidation of glucose and glycogen synthesis in the soleus muscle of rats who were fed either LA-enriched (⁺LA) or LA-deprived (⁻LA) diets, under basal conditions and in the absence or presence of insulin and/or palmitate. For 60 days, male Wistar rats were fed 1 of 4 diets consisting of ⁺LA, ⁻LA, or ⁺LA and ⁻LA supplemented with CLA. Nutritional parameters and soleus glucose metabolism were evaluated. Under basal conditions, CLA enhanced soleus glucose oxidation, whereas increased glucose uptake and incorporation were observed in the ⁻LA + CLA group. Conjugated linoleic acid–supplemented rats presented a lower response to insulin on glucose metabolism compared with non–CLA-supplemented rats. Palmitate partially inhibited the effect of insulin on the uptake and incorporation of glucose in the ⁺LA and ^–LA groups but not in the ⁺LA + CLA or ⁻LA + CLA groups. Dietary CLA increased glucose utilization under basal conditions and prevented the palmitate-induced inhibition of glucose uptake and incorporation that is stimulated by insulin. The beneficial effects of CLA were better in LA-deprived rats. Conjugated linoleic acid may also have negative effects, such as lowering the insulin response capacity. These results demonstrate the complexities of the interactions between CLA, palmitate, and/or insulin to differentially modify muscle glucose utilization and show that the magnitude of the response is related to the dietary LA levels.     

Combined effect of sesamin and α-lipoic acid on hepatic fatty acid metabolism in rats

Purpose

Dietary sesamin (1:1 mixture of sesamin and episesamin) decreases fatty acid synthesis but increases fatty acid oxidation in rat liver. Dietary α-lipoic acid lowers hepatic fatty acid synthesis. These changes can account for the serum lipid-lowering effect of sesamin and α-lipoic acid. It is expected that the combination of these compounds in the diet potentially ameliorates lipid metabolism more than the individual compounds. We therefore studied the combined effect of sesamin and α-lipoic acid on lipid metabolism in rats.

Methods

Male Sprague–Dawley rats were fed diets supplemented with 0 or 2 g/kg sesamin and containing 0 or 2.5 g/kg α-lipoic acid for 22 days.

Results and conclusions

Sesamin and α-lipoic acid decreased serum lipid concentrations and the combination of these compounds further decreased the parameters in an additive fashion. These compounds reduced the hepatic concentration of triacylglycerol, the lignan being less effective in decreasing this value. The combination failed to cause a stronger decrease in hepatic triacylglycerol concentration. The combination of sesamin and α-lipoic acid decreased the activity and mRNA levels of hepatic lipogenic enzymes in an additive fashion. Sesamin strongly increased the parameters of hepatic fatty acid oxidation enzymes. α-Lipoic acid antagonized the stimulating effect of sesamin of fatty acid oxidation through reductions in the activity of some fatty acid oxidation enzymes and carnitine concentration in the liver. This may account for the failure to observe strong reductions in hepatic triacylglycerol concentration in rats given a diet containing both sesamin and α-lipoic acid.     

Is folic acid good for everyone?

Fortification of food with folic acid to reduce the number of neural tube defects was introduced 10 y ago in North America. Many countries are considering whether to adopt this policy. When fortification is introduced, several hundred thousand people are exposed to an increased intake of folic acid for each neural tube defect pregnancy that is prevented. Are the benefits to the few outweighed by possible harm to some of the many exposed? In animals, a folic acid-rich diet can influence DNA and histone methylation, which leads to phenotypic changes in subsequent generations. In humans, increased folic acid intake leads to elevated blood concentrations of naturally occurring folates and of unmetabolized folic acid. High blood concentrations of folic acid may be related to decreased natural killer cell cytotoxicity, and high folate status may reduce the response to antifolate drugs used against malaria, rheumatoid arthritis, psoriasis, and cancer. In the elderly, a combination of high folate levels and low vitamin B-12 status may be associated with an increased risk of cognitive impairment and anemia and, in pregnant women, with an increased risk of insulin resistance and obesity in their children. Folate has a dual effect on cancer, protecting against cancer initiation but facilitating progression and growth of preneoplastic cells and subclinical cancers, which are common in the population. Thus, a high folic acid intake may be harmful for some people. Nations considering fortification should be cautious and stimulate further research to identify the effects, good and bad, caused by a high intake of folic acid from fortified food or dietary supplements. Only then can authorities develop the right strategies for the population as a whole.     

反义核酸(antisense nucleic acid)

与细胞内DNA或RNA序列相互补形成杂交体而阻断或减弱其转录和翻译过程的DNA片段或RNA片段叫反义核酸。在许多原核细胞中发现存在天然的反义RNA。反义核酸的上述性质 ,使其有可能作为药物治疗人类疾病。目前研究较多的反义核酸有反义寡核苷酸 (antisenseoligodeoxynucleotide ,ODN)、反义RNA和核酶 (ribozyme)。ODN能与双螺旋DNA结合形成三股螺旋或与局部解链的DNA单链结合而抑制DNA复制和转录。ODN可以Watson—Crick碱基配对方式与mRNA靶序列结合而阻断mRNA的加工、成熟、核 浆转移和翻译。采用基因重组技术 ,在合适的启…     

Fatty acid–binding protein-2 genotype influences lipid and lipoprotein response to eicosapentaenoic acid supplementation in hypertriglyceridemic subjects

ObjectiveThe blood lipid-lowering effects of eicosapentaenoic acid (EPA) on hypertriglyceridemic subjects with different fatty acid–binding protein-2 (FABP2) genotypes have not, to our knowledge, been previously studied.MethodsTwenty-three FABP2 Ala54 and 23 Thr54 carriers with hypertriglyceridemia (triacylglycerol level >200 mg/dL) were enrolled in this study. Participants took 2 g of pure EPA daily for 8 wk. Fasting blood lipid and lipoprotein profiles were determined and changes from baseline were measured.ResultsBlood lipids and lipoprotein responses of the FABP2 genotypes differed after EPA supplementation. Changes from baseline for triacylglycerol (19.2% decrease for Ala54 and 60.5% for Thr54, P < 0.001), very low-density lipoprotein (20.0% decrease for Ala54 and 60.5% for Thr54, P < 0.001), apolipoprotein CIII (22.8% decrease for Ala54 and 36.4% for Thr54, P < 0.01), and high-density lipoprotein cholesterol (17.6% increase for Ala54 and 30.7% for Thr54, P < 0.01) differed significantly between the two carrier groups. However, changes in total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B were not significant. EPA supplementation increased plasma EPA in Ala54 and Thr54 carriers. Although EPA supplementation increased the level of plasma EPA in both carrier groups, this effect was more pronounced in the Thr54 carriers.ConclusionTherefore, EPA consumption has more favorable effects on blood lipids of hypertriglyceridemics with Thr54 genotype rather than those with Ala54. The level of plasma EPA increases after EPA supplementation. Because the FABP2 Thr54 polymorphism appears to be prevalent in hypertriglyceridemic subjects, increasing EPA intake in these subjects could be an effective strategy for reducing blood triacylglycerol concentration.     

Is glutamine a conditionally essential amino acid?

The nonessential amino acid glutamine has recently been the focus of extensive scientific interest because of its importance in cell and tissue cultures and its physiologic role in animals and humans. Glutamine appears to be a unique amino acid, serving as a preferred respiratory fuel for rapidly proliferating cells, such as enterocytes and lymphocytes; a regulator of acid-base balance through the production of urinary ammonia; a carrier of nitrogen between tissues; and an important precursor of nucleic acids, nucleotides, amino sugars, and proteins. Abundant evidence suggests that glutamine may become a "conditionally essential" amino acid in the critically ill. During stress the body's requirements for glutamine appear to exceed the individual's ability to produce sufficient amounts of this amino acid. Provision of supplemental glutamine in specialized enteral or parenteral feeding may enhance nutritional management and augment recovery of the seriously ill while minimizing hospital stay.     

Lead poisoning in inherited δ-aminolevulinic acid dehydratase deficiency

Summary -Aminolevulinic acid dehydratase (ALA-D, respectively porphobilinogen synthase, EC 4.2.1.24) activity can be lowered by toxic, metabolic and hereditary factors. A 30-year-old painter was suffering from lead poisoning with an acute abdominal-neurologic syndrome and anemia. Blood lead was measured at 414 g/l. Urinary ALA and coproporphyrin excretion as well as erythrocyte protoporphyrin had increased extremely, whereas ALA-D activity in erythrocytes had decreased extremely to 8% of controls. Excretion parameters, protoporphyrin, hemoglobin and lead returned to normal after treatment, but four years later ALA-D activity still remained diminished (30% of controls). An inherited enzyme deficiency was assumed and found in the mother, analogous to the subnormal ALA-D activity in heterozygotes of four other families. The inherited enzyme deficiency sensitized the patient to lead exposure and intoxication, which is a toxogenetic disease in this case.     

Implications of dietary α-linolenic acid in bone health

Recent evidence implies the benefit of ω-3 polyunsaturated fatty acids in bone health. Although eicosapentaenoic acid and docosahexaenoic acid, present in fish oil, have been extensively researched, much less is known about the influence of α-linolenic acid (ALA; present in flaxseeds), a metabolic precursor of eicosapentaenoic acid and docosahexaenoic acid, on bone. Our objective was to evaluate the published literature and distinguish between the individual effects of flaxseed oil and flax lignans on bone to elucidate the exact role of ALA in skeletal biology. The search was conducted in several databases resulting in 129 articles of which 30 were eligible for inclusion in this review. The studies showed that consumption of whole flaxseeds did not lead to a marked improvement of osteoporotic bones in humans and animals. However, when combined with estrogen therapy, flaxseed supplementation offered an extra benefit to bone in animal models. Similar results were found in studies conducted with flaxseed oil (predominantly ALA), but the favorable role of flaxseed oil was more obvious in various pathologic conditions (kidney disease, obesity with insulin resistance), resulting in improved bone properties. In contrast, despite a marginal estrogenic effect, the consumption of flax lignans resulted in little benefit to bone and the effect was limited to early life of females only in animal models. Based on the available studies, it could be concluded that supplementation with flaxseeds may contribute to some improvement in osteoporotic bone properties but the bone-protective effect may be attributed to ALA, not to the lignan fraction of flaxseeds.     

Efficacy and safety of docosahexaenoic acid and arachidonic acid addition to infant formulas: can one buy better vision and intelligence?

Long chain polyunsaturated fatty acids (LCPUFA) namely arachidonic acid (ARA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3) are highly concentrated in the phospholipid bilayer of biologically active brain and retinal neural membranes and are important in phototransduction and neuronal function. The rationale for adding these LCPUFA to infant formula (IF) was primarily because of their presence in large quantities in the retina and brain and in human milk. In addition, infants fed IF containing LCPUFA and breastfed infants have comparable ARA and DHA levels in red cell and plasma, in contrast to the lower ARA and DHA levels in those fed IF containing only the essential fatty acids: linoleic (LA, 18:2n-6) and linolenic (LNA, 18:3n-3), the precursors to ARA and DHA, respectively. However, functional benefits in particular visual or neural development from IF containing LCPUFA remains controversial. Potential for excessive and/or imbalanced intake of n-6 and n-3 fatty acids exists with increasing fortification of LCPUFA to infant foods other than IF.     

δ-Aminolevulinic acid dehydratase activity,urinary δ-aminolevulinic acid concentration and zinc protoporphyrin level among people with low level of lead exposure

To evaluate the relationship of δ-aminolevulinic acid dehydratase (ALAD) activity, urinary δ-aminolevulinic acid (ALAU) level and blood zinc protoporphyrin (ZPP) concentration to low blood lead (PbB) levels, these biomarkers were determined for all subjects enrolled from a rural area of southeast China where people had low levels of exposure to lead. The mean values of PbB, ALAD, ALAU and ZPP were 67.11 μg/L (SD: 1.654, range: 10.90-514.04), 339.66 nmol ml⁻¹ h⁻¹ (1.419, 78.33-793.13), 20.64 μg/L (1.603, 2.00-326.00), and 0.14 μmol/L (3.437, 0.01-2.26), respectively. ALAD was inversely associated with low levels of PbB. ZPP was inversely related to low levels of PbB but positively related to relatively higher levels of PbB. Alcohol drinking contributed to low ALAD in men. Women had higher ZPP than men. ALAU had no significant association with PbB. In conclusion, ALAD possibly has a non-linear relation with low to moderate levels of PbB. At moderate levels of PbB, ZPP increases with increasing levels of PbB. ALAU is not suitable as an indicator for low levels of lead exposure.     

Food mineral composition and acid–base balance in rabbits

Summary Background Alkalirich diets are often recommended in human medicine to prevent the pathological consequences of nutritional acid load in conditions of impaired renal function. Aim of the study This study was undertaken in rabbits as common laboratory animals for basic medical research to explore the impact of high versus low dietary alkali intake on systemic acid–base balance and renal control in a typical herbivore. Methods Male rabbits (2.3–4.8 kg) were kept in a metabolism cage. The 24h urine and arterial blood samples were analysed for acidbase data. The metabolic CO₂ production was measured to calculate alveolar ventilation. Three randomized groups of animals were fed ad libitum with rabbit chow providing sufficient energy but variable alkali load, assessed by the ashes’ cationanion difference. Results The average daily nutritional alkali load (± SEM) was 67.1 ± 2.2 mEq · kg^–1 (N = 58) in the group on high, 45.4 ± 2.5 mEq · kg^–1 (N = 31) in the group on normal and 1.7 ± 0.5 mEq · kg^–1 (N = 11) in the group on low alkali food. Respective mean arterial base excess values (BE) were 1.4 ± 0.3 mM, 0.3 ± 0.4 mM and 0.0 ± 0.3 mM, being significantly higher on high alkali food (P < 0.05) than in the other groups. Arterial PCO₂, alveolar ventilation and metabolic CO₂ production were not significantly different between groups. On normal and high–alkali chow, an alkaline urine (pH_u > 8.0) with 18–20mmol· kg^–1 bicarbonate/carbonate was excreted daily, typically containing an insoluble precipitate of 35–60% carbonate. On low–alkali diet, the mean pH_u decreased to 6.26 ± 0.14, due to a strong reduction of daily excreted soluble bicarbonate and precipitated carbonate to 1.2 ± 0.6 and 0.7 ± 0.2mmol· kg^–1, respectively. Thereby, nearly complete fractional base reabsorption of 97.8 ± 0.7 % was reached. Conclusion Herbivore nutritional alkaliload elicited large rates of renal base excretion including precipitates, to which the urinary tract of the rabbits appeared to be adapted. Dietary base variations were more accurately reflected in the urine than by the blood acid–base status. A strongly base–deficient diet exerted maximum impact on renal base saving mechanisms, implying a critical precondition for growing susceptibility to metabolic acidosis also in the rabbit.