Eha Nurk

The Hordaland Homocysteine Study: A Community-Based Study of Homocysteine, Its Determinants, and Associations with Disease

The Hordaland Homocysteine Study (HHS) is a population-based study of more than 18,000 men and women in the county of Hordaland in Western Norway. The first investigation (HHS-I) took place in 1992-93, when the subjects were aged 40-67 y. In 1997-99, a follow-up study (HHS-II) of 7,053 subjects was carried out. In this large population, plasma levels of total homocysteine (tHcy) are associated with several physiologic and lifestyle factors and common diseases. Increasing age, male sex, smoking, coffee consumption, high blood pressure, unfavorable lipid profile, high creatinine, and the MTHFR 677C > T polymorphism are among the factors associated with increased tHcy levels; physical activity, moderate alcohol consumption, and a good folate or vitamin B-12 status are associated with lower tHcy levels. Subjects with raised tHcy levels have increased risk of cardiovascular morbidity, cardiovascular and noncardiovascular mortality, and are more likely to suffer from depression and from cognitive deficit (elderly). Among women, raised tHcy levels are associated with decreased bone mineral density and increased risk of osteoporosis. Women with raised tHcy levels also have an increased risk of having suffered from pregnancy complications and an adverse pregnancy outcome. Significant associations between tHcy and clinical outcomes are usually observed for tHcy levels > 15 micromol/L, but for most conditions, there is a continuous concentration-response relation with no apparent threshold concentration. Overall, the findings from HHS indicate that a raised tHcy level is associated with multiple clinical conditions, whereas a low tHcy level is associated with better physical and mental health.

Intake of Flavonoid-Rich Wine, Tea, and Chocolate by Elderly Men and Women Is Associated with Better Cognitive Test Performance

In a cross-sectional study, we examined the relation between intake of 3 common foodstuffs that contain flavonoids (chocolate, wine, and tea) and cognitive performance. 2031 participants (70-74 y, 55% women) recruited from the population-based Hordaland Health Study in Norway underwent cognitive testing. A cognitive test battery included the Kendrick Object Learning Test, Trail Making Test, part A (TMT-A), modified versions of the Digit Symbol Test, Block Design, Mini-Mental State Examination, and Controlled Oral Word Association Test. Poor cognitive performance was defined as a score in the highest decile for the TMT-A and in the lowest decile for all other tests. A self-reported FFQ was used to assess habitual food intake. Participants who consumed chocolate, wine, or tea had significantly better mean test scores and lower prevalence of poor cognitive performance than those who did not. Participants who consumed all 3 studied items had the best test scores and the lowest risks for poor test performance. The associations between intake of these foodstuffs and cognition were dose dependent, with maximum effect at intakes of approximately 10 g/d for chocolate and approximately 75-100 mL/d for wine, but approximately linear for tea. Most cognitive functions tested were influenced by intake of these 3 foodstuffs. The effect was most pronounced for wine and modestly weaker for chocolate intake. Thus, in the elderly, a diet high in some flavonoid-rich foods is associated with better performance in several cognitive abilities in a dose-dependent manner.

Plasma total homocysteine and memory in the elderly: The Hordaland Homocysteine study

We examined the relation between plasma total homocysteine (tHcy), folate, vitamin B12, and episodic memory in elderly community‐dwelling subjects. A population‐based study was conducted in 1992 and 1993, and subjects were re‐investigated after 6 years. Plasma analytes were determined on both occasions. At follow‐up, memory performance, using the Kendrick Object Learning Test, was investigated in 2,189 subjects (age, 65–67 years at baseline). Subjects with memory deficit (test score, <25) had higher tHcy and lower folate at follow‐up compared with those without memory deficit: 12.6 (95% confidence interval [CI], 12.1, 13.1) versus 11.5 (95% CI, 11.3, 11.6) μmol/L (p < 0.001) for tHcy, and 6.7 (95% CI, 6.2, 7.1) versus 7.6 (95% CI, 7.5, 7.8) nmol/L (p < 0.001) for folate. The risk of memory deficit increased according to quintiles of tHcy both at baseline and at follow‐up. A decline in tHcy, or an increase in folate, over a 6‐year period was associated with a higher memory test score; and vice versa. These findings indicate that increased plasma tHcy is an independent risk factor for memory deficit both cross‐sectionally and prospectively, and that a “favorable” change in folate or tHcy concentrations over time is associated with better memory performance. Ann Neurol 2005

Dietary sources of vitamin B-12 and their association with plasma vitamin B-12 concentrations in the general population: the Hordaland Homocysteine Study

BACKGROUND Limited information is available on the association between vitamin B-12 status and intake from different dietary sources. OBJECTIVE We investigated the relation of dietary intake of different food items with plasma vitamin B-12 concentrations in the general population. DESIGN A cross-sectional, population-based study of 5937 subjects in 2 age groups (47-49 and 71-74 y) from the Hordaland Homocysteine Study in Norway was conducted by using a food-frequency questionnaire and measurements of plasma vitamin B-12 concentrations. RESULTS A significant difference in plasma vitamin B-12 concentrations was observed with increasing total vitamin B-12 intake. A plateau was reached at an intake of approximately 10 microg/d. Plasma vitamin B-12 was associated with intakes of increasing amounts of vitamin B-12 from dairy products or fish (P for trend <0.001 for both) but not with intakes of vitamin B-12 from meat or eggs. For the same content of vitamin B-12, intake from dairy products led to the greatest increase in plasma vitamin B-12. Total intake of vitamin B-12, particularly from milk and fish, decreased the risk of vitamin B-12 concentrations <200 pmol/L and impaired vitamin B-12 function (vitamin B-12 <200 pmol/L and methylmalonic acid >0.27 micromol/L) in the total group and in 71-74-y-old subjects. CONCLUSIONS Dietary intake of dairy products and fish are significant contributors to plasma vitamin B-12 and may improve plasma vitamin B-12 status. Vitamin B-12 appears to be more bioavailable from dairy products; guidelines for improving vitamin B-12 status should take this into consideration.

Determinants of Plasma Methylmalonic Acid in a Large Population: Implications for Assessment of Vitamin B12 Status

BACKGROUND Methylmalonic acid (MMA) in plasma or serum is widely used for assessment of vitamin B(12) status. However, data are sparse regarding factors, besides renal function, that may influence MMA concentrations. We searched for important determinants of plasma MMA in the general population. METHODS In 6946 middle-aged (47-49 years) and elderly (71-74 years) individuals from the Hordaland Homocysteine Study in Norway, we collected anthropometric measurements, lifestyle data, and plasma MMA, vitamin B(12), and creatinine measurements. For 5820 individuals, we also collected dietary data. RESULTS Age and plasma creatinine were positively associated with plasma MMA, whereas plasma vitamin B(12) was negatively associated. These variables together with sex were the strongest determinants of plasma MMA, accounting for 16% of the variation (R(2) = 0.16). Addition of anthropometric measures and lifestyle and dietary factors only gave slight improvement (total R(2) = 0.167). Increased plasma MMA was seen when plasma vitamin B(12) was <400 pmol/L. In individuals with vitamin B(12) >or =400 micromol/L (vitamin B(12)-replete), the 2.5th-97.5th percentile reference limits for MMA were 0.10-0.28 micromol/L (middle-aged) and 0.10-0.36 micromol/L (elderly). When plotted against creatinine (nomograms), the 97.5th percentile of MMA was similar in men and women but approximately 0.15 micromol/L higher in elderly than middle-aged individuals. Vitamin B(12)-replete participants had MMA upper limits approximately 0.1 micromol/L (elderly) and 0.04 micromol/L (middle-aged) below those of the unselected population at all creatinine concentrations. CONCLUSIONS Identified determinants accounted for <17% of the overall variation in plasma MMA. The difference in MMA between middle-aged and elderly individuals is only partly explained by creatinine and vitamin B(12) concentrations.

Factor V Leiden is associated with pre-eclampsia but not with fetal growth restriction: a genetic association study and meta-analysis

Summary.  Background: Adverse pregnancy outcomes have been related to environmental and/or genetic factors. Of interest are genes associated with the clotting system as any perturbation in the balance of thrombotic and thrombolytic cascades could affect the placental circulation and hence the viability of the developing fetus. Several previous reports using relatively small numbers of cases and controls have suggested that there is a relationship between poor pregnancy outcomes and two polymorphisms, one in the factor V gene, the 1691G to A change (rs6025) located on chromosome 1q23 (factor V Leiden, FVL), and the other in the prothrombin gene, 20210G to A change (rs1799963) on chromosome 11p11‐q12 (PT). These results, however, are conflicting. Methods: We genotyped 6755 mother/infant pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC) to determine whether maternal or fetal FVL or PT, either alone or in combination, are associated with fetal growth restriction (FGR) or pre‐eclampsia (PE). We also added the present results to previous cohort studies using meta‐analysis. Results: Smoking, primiparity and lower body mass index (BMI) were all associated with FGR, but neither maternal nor fetal FVL or PT, singly or in combination, were associated with FGR in the ALSPAC cohort. Meta‐analysis confirmed the lack of association between maternal FVL and FGR with a pooled odds ratio (OR) of 1.15 [95% confidence interval (CI) 0.95–1.39]. High BMI, primiparity, diabetes and chronic hypertension were all associated with pre‐eclampsia. Combining ALSPAC results with previous studies in a meta‐analysis indicated that maternal FVL is significantly associated with pre‐eclampsia, with a pooled OR of 1.49 (95% CI 1.13–1.96). Conclusion: Neither maternal nor fetal FVL or PT, singly or in combination, are associated with FGR; this contradicts previous case–control studies and meta‐analyses based on these studies. In a meta‐analysis of all published cohort studies to date, maternal FVL appears to increase the risk of pre‐eclampsia by almost 50%. This result is robust, homogeneous and does not appear to be affected by publication bias.

Cognitive performance among the elderly in relation to the intake of plant foods. The Hordaland Health Study

Fruits and vegetables are among the most nutritious and healthy of foods, and are related to the prevention of many chronic diseases. The aim of the study was to examine the relationship between intake of different plant foods and cognitive performance in elderly individuals in a cross-sectional study. Two thousand and thirty-one elderly subjects (aged 70-74 years; 55% women) recruited from the general population in Western Norway underwent extensive cognitive testing and completed a comprehensive FFQ. The cognitive test battery covered several domains (Kendrick Object Learning Test, Trail Making Test--part A, modified versions of the Digit Symbol Test, Block Design, Mini-Mental State Examination and Controlled Oral Word Association Test). A validated and self-reported FFQ was used to assess habitual food intake. Subjects with intakes of >10th percentile of fruits, vegetables, grain products and mushrooms performed significantly better in cognitive tests than those with very low or no intake. The associations were strongest between cognition and the combined intake of fruits and vegetables, with a marked dose-dependent relationship up to about 500 g/d. The dose-related increase of intakes of grain products and potatoes reached a plateau at about 100-150 g/d, levelling off or decreasing thereafter, whereas the associations were linear for mushrooms. For individual plant foods, the positive cognitive associations of carrots, cruciferous vegetables, citrus fruits and high-fibre bread were most pronounced. The only negative cognitive association was with increased intake of white bread. In the elderly, a diet rich in plant foods is associated with better performance in several cognitive abilities in a dose-dependent manner.

Plasma stearoyl-CoA desaturase indices: association with lifestyle, diet, and body composition.

Stearoyl‐coenzyme A desaturase‐1 (SCD1) is a key enzyme in fatty acid and energy metabolism. Increased hepatic SCD1 activity is associated with obesity and obesity‐related diseases. We examined the relations of two plasma SCD activity indices (16:1n‐7/16:0, 18:1n‐9/18:0) with body composition, and the association of lifestyle and dietary variables with the plasma SCD indices.

Cognitive function in an elderly population: interaction between vitamin B12 status, depression, and apolipoprotein E ε4: the Hordaland Homocysteine Study.

Objective To investigate the cross-sectional relation between metabolic markers of vitamin B12 status and cognitive performance, and possible effect modification by the presence of depression and apolipoprotein E (ApoE) [Latin Small Letter Open E]4. Methods This is a population-based study of 1935 participants, aged 71 to 74 years, from Norway. Participants were administered a cognitive test battery, and vitamin B12 status was assessed by measurements of plasma vitamin B12, holotranscobalamin (holoTC), methylmalonic acid (MMA), and total homocysteine. Results The geometric mean (95% confidence interval) for vitamin B12 was 348 pM (341–354), whereas 5.9% of participants had vitamin B12 levels lower than 200 pM. In linear regression analyses, holoTC (p = .039) and the holoTC/vitamin B12 ratio (p = .013) were positively related, whereas MMA (p = .010) was inversely related, to global cognition, after adjustment for sex, education, ApoE status, plasma creatinine, and history of diabetes, cardiovascular disease, hypertension, and depression. Among those positive for ApoE [Latin Small Letter Open E]4, but not among those without the [Latin Small Letter Open E]4 allele, plasma vitamin B12 was positively associated with global cognition (p = .015), whereas MMA was inversely related to global cognition (p = .036) and executive function (p = .014). In participants with depression, MMA was inversely associated with global cognition (p < .001) and episodic memory (p = .001). Conclusions Among the well-nourished elderly, low vitamin B12 status is associated with cognitive deficit, particularly in those with the ApoE [Latin Small Letter Open E]4 allele or with depression.

Dietary Intake of Protein Is Positively Associated with Percent Body Fat in Middle-Aged and Older Adults

Data on associations between dietary intake of macronutrients and body composition in the general population are sparse. This population-based, cross-sectional study of 4478 middle-aged (47-49 y) and elderly (71-74 y) men and women from the Hordaland Health Study in western Norway was conducted using a validated FFQ and measurements by dual-energy X-ray absorptiometry. The relation between macronutrient intake [percentage of total energy intake (E%)] and percent body fat was investigated in the total population and in a subgroup with intermediate BMI and stable weight (BMI within the 25th-75th percentile and weight change <5% during the last 6 y; n = 975). In the total population, protein intake (E%) was associated with higher percent body fat (partial r = 0.11; P < 0.001) in multivariate linear regression analysis. In the subgroup with intermediate BMI and stable weight, there was no association between protein intake (E%) and percent body fat. Fat intake (E%) was positively associated (partial r = 0.07) whereas carbohydrate intake (E%) was inversely associated (partial r = -0.07) with percent body fat (P = 0.042 for both) in the subgroup with intermediate BMI and stable weight. Both in the total population and in the stable weight group, physical activity was inversely related to adiposity (partial r = -0.15 and -0.12, respectively; P < 0.001). Our results may explain some of the conflicting data on the effects of macronutrients in different populations and suggest the potential importance of protein intake as a factor in obesity.