Previous studies investigating protein intake in relation to mortality have provided conflicting results.
We investigated the associations of dietary protein and protein sources with risk of disease ...death in the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study.
The study population consisted of 2641 Finnish men, aged 42–60 y at baseline in 1984–1989. We estimated protein intakes with 4-d dietary records at baseline and collected data on disease deaths from the national Causes of Death Register. Cox proportional hazards regression models were used to estimate HRs and 95% CIs.
During the average follow-up of 22.3 y, we observed 1225 deaths due to disease. Higher intakes of total protein and animal protein had borderline statistically significant associations with increased mortality risk: multivariable-adjusted HR (95% CI) in the highest compared with the lowest quartile for total protein intake=1.17 (0.99, 1.39; P-trend across quartiles=0.07) and for animal protein intake=1.13 (0.95, 1.35; P-trend=0.04). Higher animal-to-plant protein ratio (extreme-quartile HR=1.23; 95% CI: 1.02, 1.49; P-trend=0.01) and higher meat intake (extreme-quartile HR=1.23; 95% CI: 1.04, 1.47; P-trend=0.01) were associated with increased mortality. When evaluated based on disease history at baseline, the association of total protein with mortality appeared more evident among those with a history of type 2 diabetes, cardiovascular disease, or cancer (n=1094) compared with those without disease history (n=1547) (P-interaction=0.05 or 0.07, depending on the model). Intakes of fish, eggs, dairy, or plant protein sources were not associated with mortality.
Higher ratio of animal to plant protein in diet and higher meat intake were associated with increased mortality risk. Higher total protein intake appeared to be associated with mortality mainly among those with a predisposing disease. This trial was registered at clinicaltrials.gov as NCT03221127.
The roles of different dietary proteins in the aetiology of type 2 diabetes (T2D) remain unclear. We investigated the associations of dietary proteins with the risk of incident T2D in Finnish men ...from the prospective Kuopio Ischaemic Heart Disease Risk Factor Study. The study included 2332 men aged 42-60 years at the baseline examinations in 1984-1989. Protein intakes were calculated from 4-d dietary records. Incident T2D was determined by self-administered questionnaires, fasting blood glucose measurements, 2-h oral glucose tolerance tests, and with national registers. The multivariable-adjusted risk of T2D on the basis of protein intakes was compared by the Cox proportional hazard ratios (HR). During the mean follow-up of 19·3 years, 432 incident T2D cases were identified. Total, animal, meat or dairy product protein intakes were not associated with risk of T2D when the potential confounders were accounted for. Plant (multivariable-adjusted extreme-quartile HR 0·65; 95 % CI 0·42, 1·00; P trend 0·04) and egg (HR 0·67; 95 % CI 0·44, 1·00; P trend 0·03) protein intakes were associated with a decreased risk of T2D. Adjustments for BMI, plasma glucose and serum insulin slightly attenuated associations. Replacing 1 % energy from carbohydrates with energy from protein was associated with a 5 % (95 % CI 0, 11) increased risk of T2D, but adjustment for fibre intake attenuated the association. Replacing 1 % of energy from animal protein with energy from plant protein was associated with 18 % (95 % CI 0, 32) decreased risk of T2D. This association remained after adjusting for BMI. In conclusion, favouring plant and egg proteins appeared to be beneficial in preventing T2D.
Moderate egg intake has been associated with better cognitive performance in observational studies. This association may be due to the rich content of choline, especially phosphatidylcholine, in eggs ...because choline has been suggested to have a role in the prevention of cognitive decline.
We investigated the associations of dietary choline intake with the risk of incident dementia and with cognitive performance in middle-aged and older men in the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study.
A population-based sample of 2497 dementia-free men aged 42–60 y was examined in 1984–1989. A subset of 482 men completed 5 different cognitive performance tests 4 y later. Dementia and Alzheimer disease diagnoses were retrieved from Finnish health registers. Dietary intakes were assessed with the use of 4-d food records at baseline. Cox regression and ANCOVA were used for the analyses. All analyses were also stratified by the apolipoprotein E phenotype (APOE-ε4 compared with other phenotypes). These data were available for 1259 men.
The mean ± SD total choline intake was 431 ± 88 mg/d, of which 188 ± 63 mg/d was phosphatidylcholine. During a 21.9-y follow-up, 337 men were diagnosed with dementia. Those in the highest compared with the lowest phosphatidylcholine intake quartile had 28% (95% CI: 1%, 48%; P-trend = 0.02 across quartiles) lower multivariable-adjusted risk of incident dementia. Total choline intake had no association with the risk of incident dementia. However, both total choline and phosphatidylcholine intakes were associated with better performance in cognitive tests assessing frontal and temporal lobe functioning. For example, higher intakes were associated with better performance in verbal fluency and memory functions. The APOE phenotype had little or no impact on the associations.
Higher phosphatidylcholine intake was associated with lower risk of incident dementia and better cognitive performance in men in eastern Finland. This trial was registered at clinicaltrials.gov as NCT03221127.
Vitamin D3 has transcriptome- and genome-wide effects and activates, via the binding of its metabolite 1α,25-dihydroxyvitamin D3 to the transcription factor vitamin D receptor (VDR), several hundred ...target genes. Using samples from a 5-month vitamin D3 intervention study (VitDmet), we recently reported that the expression of 12 VDR target genes in peripheral blood mononuclear cells (PBMCs) as well as 12 biochemical and clinical parameters of the study participants are significantly triggered by vitamin D3. In this study, we performed a more focused selection of further 12 VDR target genes and demonstrated that changes of their mRNA expression in PBMCs of VitDmet subjects significantly correlate with alterations of 25-hydroxyvitamin D3 serum levels. Network and self-organizing map analysis of these datasets together with that of the other 24 parameters was followed by relevance calculations and identified changes in parathyroid hormone serum levels and the expression of the newly selected genes STS, BCL6, ITGAM, LRRC25, LPGAT1 and TREM1 as well as of the previously reported genes DUSP10 and CD14 as the most relevant parameters for describing vitamin D responsiveness in vivo. Moreover, parameter relevance ranking allowed the segregation of study subjects into high and low responders. Due to the long intervention period the vitamin D response was not too prominent on the level of transcriptional activation. Therefore, we performed in the separate VitDbol trial a short-term but high dose stimulation with a vitamin D3 bolus. In PBMCs of VitDbol subjects we observed direct transcriptional effects on the selected VDR target genes, such as an up to 2.1-fold increase already one day after supplementation onset. In conclusion, both long-term and short-term vitamin D3 supplementation studies allow monitoring the vitamin D responsiveness of human individuals and represent new types of human in vivo vitamin D3 investigations.
Background: Although higher intakes of fruit, berries, and vegetables (FBV) have been associated with reduced risk of type 2 diabetes (T2D) in some observational studies, the evidence is limited and ...inconclusive.Objective: We assessed the relation of FBV intake and T2D incidence in Finnish men.Design: We studied 2332 men from the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study who were aged 42–60 y and free of T2D or impaired fasting glucose at baseline in 1984–1989. Food intake was assessed with 4-d food recording. T2D was assessed by using self-administered questionnaires, a fasting blood glucose measurement, a 2-h oral-glucose-tolerance test, and record linkage to a reimbursement register on diabetes medication expenses. In the Cox proportional hazards model, HRs for T2D were computed for the highest compared with lowest quartiles of FBV intake adjusted for age, examination year, body mass index, waist-to-hip ratio, smoking, education, physical activity, family history of diabetes, and energy and alcohol intakes.Results: During the mean follow-up time of 19.3 y, 432 new cases of T2D occurred. For the total FBV intake (with the exclusion of potatoes and fruit and berry juices), the extreme-quartile multivariable-adjusted HR for T2D was 0.76 (95% CI: 0.57, 1.02; P-trend = 0.15). In the analysis for FBV components, berries had a corresponding HR of 0.65 (95% CI: 0.49, 0.88; P-trend = 0.003), whereas no significant associations were shown for fruit, fruit and berry juices, and vegetables.Conclusion: Fruit and vegetables, particularly berries, may reduce risk of T2D in men.
•Replacing saturated fat with polyunsaturated fat is recommended for CHD prevention.•Several trials in the 1950s-1970s tested this diet-heart hypothesis.•Recently recovered data from two of the ...trials challenged the hypothesis.•Many of the old trials had limitations, which prevents drawing firm conclusions.
Several trials in the 1950s through 1970s tested the hypothesis that replacing saturated fat in the diet predominantly with n-6 polyunsaturated fat (PUFA) would reduce the incidence of coronary heart disease (CHD), mainly through modifying blood lipid profile. Most of these trials did observe a reduction in serum total cholesterol in the intervention group, but many trials failed to find a significant reduction in the incidence of CHD. However, some meta-analyses have found a reduced incidence of CHD by pooling the results from the trials. Recently, new recovered and reanalyzed data has emerged from two of the old trials. The new findings seemed to counteract the classical diet-heart hypothesis, when they found no cardiovascular benefit and even suggested harm, despite reduction in the serum total cholesterol concentration after replacing saturated fat especially with n-6 PUFA. This has raised criticism regarding the validity of the dietary recommendations that suggest partially replacing saturated fats with n-6 PUFA. This paper introduces the classical diet-heart trials and their main results and how the new findings relate to the overall study data of the cardiovascular effects of the n-6 PUFA. For multiple reasons considered here, it is difficult to draw firm conclusions of the cardiovascular effects of the n-6 PUFA based only on the findings in the old diet-heart trials. A more comprehensive picture emerges when also other lines of evidence is considered. The overall study data, including findings also from prospective cohort studies and from dietary trials with intermediate outcomes, still suggests that replacing saturated fat with n-6 PUFA would rather be beneficial than harmful for the prevention of CHD.
•In human PBMCs 702 genes are significantly (p < 005) affected by a vitamin D3 bolus.•These genes are involved in general protein translation, monocyte differentiation and cellular growth ...control.•The expression pattern of vitamin D target genes differed significantly between individuals.
In the vitamin D intervention study VitDbol (NCT02063334) blood samples were drawn directly before an oral bolus (2000 μg vitamin D3) and 24 h later. The focus of phase II of VitDbol was the transcriptome-wide analysis of the effects of vitamin D gene expression in human peripheral blood mononuclear cells (PBMCs). All five participants responded in an individual fashion to the bolus by increases in serum levels of the vitamin D metabolites 25-hydroxyvitamin D3 (25(OH)D3) and 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). RNA sequencing identified 15.040 commonly expressed genes in PBMCs, 702 (4,7%) of which were significantly (p < 0,05) affected by the vitamin D3 bolus. KEGG pathway analysis suggested that these genes are involved in general protein translation, monocyte differentiation and cellular growth control. Previously published transcriptome-wide studies in comparable cell systems confirmed 234 of the 702 vitamin D target genes, leaving many genes, such as HLA-A and HLA-C, as novel discoveries. Interestingly, in vivo stimulated PBMCs of this study showed a larger number of common vitamin D target genes with the monocytic cell line THP-1 than with in vitro stimulated PBMCs. The expression pattern of vitamin D target genes differed significantly between individuals and the average expression change can serve as a marker for vitamin D responsiveness. In conclusion, this study demonstrates that under in vivo conditions changes in 25(OH)D3 and 1,25(OH)2D3 serum concentrations alter the expression of more than 700 vitamin D target genes in human leukocytes.
Experimental data suggest that egg intake could have a beneficial impact on several risk factors for type 2 diabetes. In contrast, some recent epidemiological studies have concluded that egg ...consumption may increase diabetes risk. We performed a dose-response meta-analysis of prospective cohorts on the relation of egg consumption with incident type 2 diabetes. We searched for cohort studies that assessed egg consumption and diabetes risk up to June 2015. We identified 416 articles and extracted data independently and in duplicate from ten eligible studies. We used random-effects generalised least squares models for pooled dose-response estimation based on thirteen estimates. Our study included 251 213 individuals and 12 156 incident type 2 diabetes cases. Egg intake was associated with incident type 2 diabetes (risk ratio (RR)/egg per d 1·13; 95 % CI 1·04, 1·22). We identified study location as a major source of heterogeneity. For studies conducted in the USA, we observed a stronger association (RR 1·47; 95 % CI 1·32, 1·64), whereas results were null for studies conducted elsewhere. Studies considered to be of high quality yielded null findings (RR 0·94; 95 % CI 0·74, 1·19). The association of egg intake with increased risk of incident type 2 diabetes may be restricted to US cohort studies. There are limited data to support a biological mechanism that could underlie this association; thus, the possibility that these results may be due to residual confounding by dietary behaviours restricted to certain populations cannot be excluded.
Meat is not only a source of several nutrients but also a proposed risk factor for several non-communicable diseases. Here, we describe the totality of evidence for the role of meat intake for ...chronic disease outcomes, discuss potential mechanistic pathways, knowledge gaps, and limitations of the literature. Use of the scoping review is based on a
systematic review (SR) and meta-analysis on the association between poultry intake and cardiovascular disease (CVD) and type 2 diabetes (T2D), qualified SRs (as defined in the Nordic Nutrition Recommendations 2023 project) on meat intake and cancer by the World Cancer Research Fund (WCRF), the International Agency for Research on Cancer (IARC), and a systematic literature search of SRs and meta-analyses. The quality of the SRs was evaluated using a modified AMSTAR 2 tool, and the strength of evidence was evaluated based on a predefined criteria developed by the WCRF. The quality of the SRs was on average critically low. Our findings indicate that the evidence is too limited for conclusions for most of the chronic disease outcomes. However, findings from qualified SRs indicate strong evidence that processed meat increases the risk of colorectal cancer and probable evidence that red meat (unprocessed, processed, or both) increases the risk. The evidence suggests that both unprocessed red meat and processed meat (also including processed poultry meat) are probable risk factors for CVD mortality and stroke, and that total red meat and processed meat are risk factors for CHD. We found no sufficient evidence suggesting that unprocessed red meat, processed red meat, total red meat, or processed meat (including red and white meat) would be protective of any chronic disease. There was also no sufficient evidence to conclude on protective effect of poultry on any chronic diseases; effects on the risk of CVD, stroke, and T2D, to any direction, were regarded as unlikely.
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.
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.
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.
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).
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.
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