Anu Ruusunen

Dietary Folate and the Risk of Depression in Finnish Middle-Aged Men

Background: Several cross-sectional studies have focused on the low blood folate levels of depressive patients. Nevertheless, no prospective studies have been published on the association between dietary folate and depression. Methods: We studied the association between dietary folate and cobalamin and receiving a discharge diagnosis of depression in a prospective follow-up setting. Our cohort was recruited between 1984 and 1989 and followed until the end of 2000, and it consisted of 2,313 men aged between 42and 60 years from eastern Finland. Results: The mean intake of folate in the whole cohort was 256 µg/day (SD = 76). Those below the median of energy-adjusted folate intake had higher risk of getting discharge diagnosis of depression (RR 3.04, 95% CI: 1.58, 5.86) during the follow-up period than those who had a folate intake above the median. This excess risk remained significant after adjustment for current socioeconomic status, the baseline HPL depression score, the energy-adjusted daily intake of fibre and vitamin C, and the total fat intake. Conclusions: A low dietary intake of folate may be a risk factor for severe depression. This also indicates that nutrition may have a role in the prevention of depression.

Coffee, tea and caffeine intake and the risk of severe depression in middle-aged Finnish men: the Kuopio Ischaemic Heart Disease Risk Factor Study

OBJECTIVE Only a few cross-sectional studies have assessed the association between coffee, tea and caffeine and the risk of depression. Our aim was to determine the association in a population-based cohort study. DESIGN The population-based Kuopio Ischaemic Heart Disease Risk Factor Study cohort was recruited between 1984 and 1989 and followed until the end of 2006. We investigated the association between the intake of coffee, tea and caffeine and depression. SETTING Eastern Finland. SUBJECTS Middle-aged men (n 2232). RESULTS Altogether, forty-nine men received a discharge diagnosis of depression. We classified subjects into quartiles according to their mean daily coffee intake: non-drinkers (n 82), light drinkers (<375 ml/d, n 517), moderate drinkers (375-813 ml/d, n 1243) and heavy drinkers (>813 ml/d, n 390). Heavy drinkers had a decreased risk (RR = 0.28, 95 % CI 0.08, 0.98) for depression when compared with non-drinkers, after adjustment for age and examination years. Further adjustment for socio-economic status, alcohol consumption, smoking, maximal oxygen uptake, BMI and the energy-adjusted daily intakes of folate and PUFA did not attenuate this association (relative risk (RR) = 0.23, 95 % CI 0.06, 0.83). No associations were observed between depression and intake of tea (drinkers v. non-drinkers; RR = 1.19, 95 % CI 0.54, 2.23) or caffeine (highest quartile v. lowest quartile; RR = 0.99, 95 % CI 0.40, 2.45). CONCLUSIONS Coffee consumption may decrease the risk of depression, whereas no association was found for tea and caffeine intake.

The intake of flavonoids and carotid atherosclerosis: the Kuopio Ischaemic Heart Disease Risk Factor Study

The role of flavonoids in CVD is still unclear. In this cross-sectional study we assessed the relation between the intakes of twenty-six flavonoids from five subclasses: flavonols, flavones, flavanones, flavan-3-ols and anthocyanidins, and the mean common carotid artery intima-media thickness (CCA-IMT). The study population consisted of 1380 middle-aged eastern Finnish men for whom the mean CCA-IMT examinations were carried out as a part of the prospective population-based Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD). The mean intake of flavonoids was 128.5 (sd 206.7) mg/d and the mean CCA-IMT was 0.78 (sd 0.17) mm. In the lowest quartile of total flavonoid intake the non-adjusted mean CCA-IMT was 0.79 (sd 0.19) mm, while the mean CCA-IMT was 0.76 (sd 0.15) in the highest quartile (P < 0.001). After adjustment for age, variables related to CCA-IMT measurement, history of atherosclerosis, smoking, BMI, diabetes, systolic blood pressure, serum HDL- and LDL-cholesterol, VO2 max, and intakes of alcohol, SFA, folate, vitamins C and E, the total flavonoid intake was inversely associated with the mean CCA-IMT (P = 0.018). Out of different flavonoid subclasses, flavan-3-ols were inversely associated with CCA-IMT (P = 0.025) after statistical adjustment. There was a trend for an inverse association between intake of flavonols and mean CCA-IMT (P = 0.055). We conclude that high intake of flavonoids is associated with decreased carotid atherosclerosis in middle-aged Finnish men.

Dietary recommendations for the prevention of depression

Background: Major depressive disorder is a common, chronic condition that imposes a substantial burden of disability globally. As current treatments are estimated to address only one-third of the disease burden of depressive disorders, there is a need for new approaches to prevent depression or to delay its progression. While in its early stages, converging evidence from laboratory, population research, and clinical trials now suggests that dietary patterns and specific dietary factors may influence the risk for depression. However, largely as a result of the recency of the nutritional psychiatry field, there are currently no dietary recommendations for depression. Aim: The aim of this paper is to provide a set of practical dietary recommendations for the prevention of depression, based on the best available current evidence, in order to inform public health and clinical recommendations. Results: Five key dietary recommendations for the prevention of depression emerged from current published evidence. These comprise: (1) follow ‘traditional’ dietary patterns, such as the Mediterranean, Norwegian, or Japanese diet; (2) increase consumption of fruits, vegetables, legumes, wholegrain cereals, nuts, and seeds; (3) include a high consumption of foods rich in omega-3 polyunsaturated fatty acids; (4) replace unhealthy foods with wholesome nutritious foods; (5) limit your intake of processed-foods, ‘fast’ foods, commercial bakery goods, and sweets. Conclusion: Although there are a number of gaps in the scientific literature to date, existing evidence suggests that a combination of healthful dietary practices may reduce the risk of developing depression. It is imperative to remain mindful of any protective effects that are likely to come from the cumulative and synergic effect of nutrients that comprise the whole-diet, rather than from the effects of individual nutrients or single foods. As the body of evidence grows from controlled intervention studies on dietary patterns and depression, these recommendations should be modified accordingly.

Dietary zinc intake and the risk of depression in middle-aged men: A 20-year prospective follow-up study

BACKGROUND Zinc is an immunomodulatory trace element suggested to be beneficial in the augmentation of antidepressant therapy. Cross-sectional studies have also suggested an association between low dietary zinc and depression. This study examined the association between dietary zinc intake and depression in a prospective setting in initially depression-free men during a 20-year follow-up. METHODS The study formed a part of the population-based Kuopio Ischemic Heart Disease Risk Factor (KIHD) Study, and comprised 2317 Finnish men aged 42-61 years. Zinc intake was assessed at baseline by a 4-d food record. Baseline depression severity was recorded with the Human Population Laboratory Depression Scale. In the prospective setting, depression was defined as having received a hospital discharge diagnosis of unipolar depressive disorder. Individuals who at baseline had elevated depressive symptoms were excluded (n=283). RESULTS Altogether, 60 (2.7%) individuals received a hospital discharge diagnosis of depression during the 20-year follow-up. In Cox regression analysis adjusted for age, baseline depression severity, smoking, alcohol use, physical exercise and the use of dietary supplements, belonging to the lowest tertile of energy-adjusted zinc intake was not associated with an increased depression risk (RR 1.06, 95% CI 0.59-1.90). LIMITATIONS These observations may not be generalizable to women, or to individuals with a depression level not warranting hospitalization. CONCLUSIONS Our findings suggest that a low dietary zinc intake may not longitudinally precede depression in men. Dietary zinc intake may not have relevance for the prevention of depression in middle-aged men with a sufficient dietary zinc intake.

How does lifestyle intervention affect depressive symptoms? Results from the Finnish Diabetes Prevention Study.

Diabet. Med. 29, e126–e132 (2012)

Serum n–6 polyunsaturated fatty acids, Δ5- and Δ6-desaturase activities, and risk of incident type 2 diabetes in men: the Kuopio Ischaemic Heart Disease Risk Factor Study

BACKGROUND The role of n-6 (ω-6) polyunsaturated fatty acids (PUFAs) in type 2 diabetes (T2D) is inconclusive. In addition, little is known about how factors involved in PUFA metabolism, such as zinc, may affect the associations. OBJECTIVES We investigated the associations of serum n-6 PUFAs and activities of enzymes involved in PUFA metabolism, Δ5 desaturase (D5D) and Δ6 desaturase (D6D), with T2D risk to determine whether serum zinc concentrations could modify these associations. DESIGN The study included 2189 men from the prospective Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60 y and free of T2D at baseline in 1984-1989. T2D was assessed by self-administered questionnaires, by fasting and 2-h oral-glucose-tolerance test blood glucose measurement at re-examination rounds 4, 11, and 20 y after baseline, and by record linkage to the hospital discharge registry and the reimbursement register on diabetes medication expenses. Multivariate-adjusted Cox proportional hazards regression models were used to analyze associations. RESULTS During the average follow-up of 19.3 y, 417 men developed T2D. Those with higher estimated D5D activity (extreme-quartile HR: 0.55; 95% CI: 0.41, 0.74; P-trend < 0.001) and higher concentrations of total n-6 PUFAs (HR: 0.54; 95% CI: 0.41, 0.73; P-trend < 0.001), linoleic acid (LA; HR: 0.52; 95% CI: 0.39, 0.70; P-trend < 0.001), and arachidonic acid (AA; HR: 0.62; 95% CI: 0.46, 0.85; P-trend = 0.007) had a lower risk and those with higher concentrations of γ-linolenic acid (GLA; HR: 1.28; 95% CI: 0.98, 1.68; P = 0.021) and dihomo-γ-linolenic acid (DGLA; HR: 1.38; 95% CI: 1.04, 1.84; P-trend = 0.005) and higher D6D activity had a higher (HR: 1.50; 95% CI: 1.14, 1.97; P-trend < 0.001) multivariate-adjusted risk of T2D. Zinc mainly modified the association with GLA on T2D risk, with a higher risk observed among those with serum zinc concentrations above the median (P-interaction = 0.04). CONCLUSIONS Higher serum total n-6 PUFA, LA, and AA concentrations and estimated D5D activity were associated with a lower risk of incident T2D, and higher GLA and DGLA concentrations and estimated D6D activity were associated with a higher risk. In addition, a higher serum zinc concentration modified the association of GLA on the risk of T2D.

Purine metabolism is dysregulated in patients with major depressive disorder

INTRODUCTION The purine cycle and altered purinergic signaling have been suggested to play a role in major depressive disorder (MDD). Nevertheless, data on this topic are scarce. Based on previous studies, we hypothesized that compared with non-depressed controls, MDD patients have distinct purine metabolite profiles. METHODS The samples comprised 99 MDD patients and 253 non-depressed controls, aged 20-71 years. Background data were collected with questionnaires. Fasting serum samples were analyzed using ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) to determine seven purine cycle metabolites belonging to the purine cycle. We investigated the levels of these metabolites in three settings: (1) MDD patients vs. non-depressed controls and (2) remitted vs. non-remitted MDD patients, and also (3) within-group changes in metabolite levels during the follow-up period. RESULTS In logistic regression adjusted for age, gender, smoking, alcohol use, physical exercise, glycosylated hemoglobin, and high-density lipoprotein cholesterol, lower levels of inosine (OR 0.89, 95% CI 0.82-0.97) and guanosine (OR 0.32, 95% CI 0.17-0.59), and higher levels of xanthine (OR 2.21, 95% CI 1.30-3.75) were associated with MDD vs. the non-depressed group. Levels of several metabolites changed significantly during the follow-up period in the MDD group, but there were no differences between remitted and non-remitted groups. CONCLUSIONS We observed altered purine metabolism in MDD patients compared with non-depressed controls. Furthermore, our observations suggest that circulating xanthine may accumulate in MDD patients.

Serum zinc and risk of type 2 diabetes incidence in men: The Kuopio Ischaemic Heart Disease Risk Factor Study

OBJECTIVES Zinc may play a role in the development of type 2 diabetes (T2D), because it is involved in antioxidant and anti-inflammatory activities. However, the role of zinc in the etiology of T2D has been poorly investigated. This study was conducted to study the association of serum zinc on T2D risk in middle-aged and older Finnish men. METHODS This was a 20-year prospective follow-up study on 2220 Finnish men from the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) who were 42 to 60 years old at baseline in 1984-1989. The main outcome was incident T2D. Serum zinc, body mass index (BMI), fasting blood glucose (FBG), serum insulin, C-reactive protein (CRP) and, in a subset of 751 participants, insulin-like growth factor-binding protein-1 (IGFBP-1), were measured. Also, the homeostatic model assessment (HOMA) was used to quantify insulin resistance (HOMA-IR), beta-cell function (HOMA-β) and insulin sensitivity (HOMA-IS). RESULTS At baseline, serum zinc was associated with higher BMI, serum insulin, HOMA-IR, HOMA-β and IGFBP-1 and lower HOMA-IS. During the average follow-up of 19.3 years, 416 men developed T2D. Men in the highest quartile of serum zinc had 60% higher risk (95% CI 20-113%; P-trend<0.001) for incident T2D compared with the men in the lowest quartile, after multivariate adjustments. This association was attenuated after adjustment for BMI (HR=1.39, 95% CI 1.04-1.85; P-trend=0.013) or HOMA-IS (HR=1.38, 95% CI 1.04-1.83; P-trend=0.015), whereas adjustment for the other factors had only modest impact on the association. CONCLUSION Higher serum zinc was associated with higher risk of T2D; effects of zinc on BMI and insulin sensitivity may partly explain the association. Further prospective studies are warranted to confirm our results and explore potential mechanisms.

Dietary magnesium intake and the incidence of depression: A 20-year follow-up study.

BACKGROUND Depression is a major global public health concern. The aetiology of depression is partly unclear; however, intake of nutrients, such as magnesium, have been suggested to affect depressive symptoms and modify depression risk. METHODS This research is a part of the Kuopio Ischemic Heart Disease Risk Factor (KIHD) Study, conducted on a sample of 2320 Eastern Finnish men aged 42-61 years old at the baseline. Magnesium intake was assessed by a 4-day food record. Hospital discharge diagnosis of unipolar depressive disorder was used as an outcome variable. RESULTS Participants in the middle tertile of dietary magnesium intake had a statistically significantly decreased risk of getting a hospital discharge diagnosis of depression compared to participants in the lowest tertile of magnesium intake (HR 0.49, CI 0.25-0.95, P=0.035) in the prospective setting after multivariable adjustments. In addition, an inverse association between magnesium intake and the risk of depression was found when the combined middle and highest tertiles of magnesium intake were compared with the lowest tertile (HR 0.53, CI 0.29-0.95, P=0.033). LIMITATIONS Our findings may not be generalizable to individuals below middle-age or women. Moreover, we were unable to consider cases with mild depression in the longitudinal setting. CONCLUSIONS The results of this study suggest that magnesium intake may have an effect on the risk to develop depression. Further studies are needed to investigate whether sufficient magnesium intake could have implications for prevention or treatment of depression.