Tommy Cederholm | Uppsala University (original) (raw)

Papers by Tommy Cederholm

The American Journal of Clinical Nutrition, 2008

Background: Desaturase indexes, as markers of endogenous fatty acid desaturation, and a character... more Background: Desaturase indexes, as markers of endogenous fatty acid desaturation, and a characteristic serum fatty acid (FA) composition are related to cardiovascular and metabolic diseases, but the relation to mortality is poorly investigated. Objective: The objective was to evaluate the relation between dietary fat biomarkers, desaturase indexes, and mortality. Design: In this community-based prospective sample, 50-y-old men were followed for a maximum of 33.7 y. Cox proportional hazard analysis was conducted to investigate desaturase indexes (stearoyl-CoA-desaturase and ⌬ 6-and ⌬ 5-desaturase) and the relation of individual serum esterified fatty acids (FAs) in relation to total and cardiovascular mortality in the total study sample (n ҃ 2009) and in a healthy subsample (n ҃ 1885). Desaturase indexes were estimated as product-to-precursor FA ratios. Results: During follow-up, 1012 men in the total sample died and 931 men in the healthy subsample died. Desaturase indexes predicted both total and cardiovascular mortality. The relations were independent of smoking status, physical activity, BMI, total cholesterol, and hypertension. The adjusted and standardized (per SD) hazard ratios (HRs) and 95% CIs for cardiovascular mortality were 1.15 (1.04, 1.27) for stearoyl-CoA-desaturase, 1.12 (1.0, 1.24) for ⌬ 6-desaturase, and 0.88 (0.80, 0.98) for ⌬ 5-desaturase, respectively. The proportion of serum linoleic acid was inversely related, whereas serum FAs associated with saturated fat intake (palmitic, palmitoleic, and dihomo-␥-linolenic acids) were directly related to total and cardiovascular mortality. Conclusions: Altered endogenous FA desaturation might contribute to mortality risk because we observed independent associations between desaturase activity indexes and mortality. The proportion of linoleic acid was inversely related, and FAs reflecting saturated fat intake were directly related to mortality.

Circulation, Nov 25, 2014

Increased intake of certain polyunsaturated fatty acids (PUFA) in place of saturated fatty acids ... more Increased intake of certain polyunsaturated fatty acids (PUFA) in place of saturated fatty acids has shown beneficial effects on cardiovascular disease (CVD) risk, although results are inconsistent. This may partly be explained by sex differences and shortcomings with self-reported intake data. The objective was to evaluate associations between markers of PUFA intake, from vegetable oils and fish, with CVD incidence and mortality (all-cause). In a representative population-based prospective cohort study including 2193 women and 2039 men (all aged 60 y) in Stockholm County, Sweden, PUFA were measured in serum cholesteryl esters by gas chromatography at baseline (1997-1998). Using national registers, 484 first CVD events (male, n=294; female, n=190) and 456 deaths (n=265; n=191) were identified during follow-up (median 14.5y), in individuals without prior CVD events at baseline. Associations between PUFA intake (assessed by circulating PUFA [linoleic acid, LA; α-linolenic acid, ALA; eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA]) and risk of CVD and mortality were evaluated in men and women separately and together, by Cox proportional hazard models. Hazard ratios (HR) with 95% confidence interval (95%CI) were estimated in crude models and after adjusting for BMI, sex, education, smoking, physical activity, alcohol intake, diabetes, hypertension, and hypercholesterolemia. In the whole population, EPA and DHA were inversely associated with mortality risk in adjusted model; 1 SD increment in EPA and DHA decreased the risk of mortality by 21% (HR 0.79 [95%CI 0.65-0.96]) and 22% (0.78 [0.66, 0.93]), respectively. Among women, EPA and DHA were associated with reduced CVD risk (HR 0.79 [95% CI 0.64-0.97] and 0.74 [0.61-0.89], respectively), whereas women with high ALA levels had moderately increased risk of CVD (1.16 [1.02-1.32]). High LA levels were associated with reduced mortality in men (0.73 [0.64-0.83]). In line with some previous studies, circulating PUFA reflecting dietary n-3 and n-6 PUFA intake were in general inversely linked with CVD and/or mortality. Sex specific relations between PUFA and CVD/mortality motivate further investigations and may partly explain previous inconsistencies regarding dietary PUFA in CVD prevention.

Journal of Nephrology, 2020

Background In persons with CKD, adherence to plant-based diets is associated with lower risk of C... more Background In persons with CKD, adherence to plant-based diets is associated with lower risk of CKD progression and death, but underlying mechanisms are poorly characterized. We here explore associations between adherence to plant-based diets and measures of insulin sensitivity and inflammation in men with CKD stages 3–5. Methods Cross-sectional study including 418 men free from diabetes, aged 70–71 years and with cystatin-C estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 and not receiving kidney-specific dietetic advice. Information from 7-day food records was used to evaluate the adherence to a plant-based diet index (PBDi), which scores positively the intake of plant-foods and negatively animal-foods. Insulin sensitivity and glucose disposal rate were assessed with the gold-standard hyperinsulinemic euglycemic glucose clamp technique. Inflammation was evaluated by serum concentrations of C-reactive protein (CRP) and interleukin (IL)-6. Associations were explored ...

Nutrients, 2019

To date, little is known about how dietary patterns may link to measures of sleep quality in olde... more To date, little is known about how dietary patterns may link to measures of sleep quality in older subjects, who often suffer from sleep problems. Here, we investigated, in an older male population from Sweden (n = 970; aged 71 ± 1 year), whether adherence to the Healthy Diet Indicator (HDI; based on recommendations from the World Health Organization) or the Mediterranean Diet (MD) is linked to sleep disturbances. The diet scores were calculated using a seven-day food diary, and self-reported sleep initiation or maintenance problems were assessed by questionnaires. When adjusted for potential confounders, no associations between dietary scores and sleep parameters were found. In contrast, low consumption of milk and dairy products —one of the dietary features of the MD —was associated with better subjective sleep initiation. This association was, however, not found in men with adequate reports of daily energy intake (~54% of the cohort). To summarize, our findings do not suggest tha...

Journal of the American Geriatrics Society, 2017

ObjectivesTo examine the longitudinal associations between aging with preserved functionality, i.... more ObjectivesTo examine the longitudinal associations between aging with preserved functionality, i.e. independent aging and survival, and lifestyle variables, dietary pattern and cardiovascular risk factors.DesignCohort study.SettingUppsala Longitudinal Study of Adult Men, Sweden.ParticipantsSwedish men (n = 1,104) at a mean age of 71 (range 69.4–74.1) were investigated, 369 of whom were evaluated for independent aging 16 years later, at a mean age of 87 (range 84.8–88.9).MeasurementsA questionnaire was used to obtain information on lifestyle, including education, living conditions, and physical activity. Adherence to a Mediterranean‐like diet was assessed according to a modified Mediterranean Diet Score derived from 7‐day food records. Cardiovascular risk factors were measured. Independent aging at a mean age of 87 was defined as lack of diagnosed dementia, a Mini‐Mental State Examination score of 25 or greater, not institutionalized, independence in personal activities of daily livi...

The American journal of clinical nutrition, 2017

Background: Vitamin D has been implicated as being important for maintaining cognitive function i... more Background: Vitamin D has been implicated as being important for maintaining cognitive function in old age. Results from longitudinal studies examining the association of vitamin D with incident dementia and cognitive impairment have been inconsistent.Objective: We investigated the relation between vitamin D, assessed in 3 different ways, and the risk of dementia.Design: We measured plasma 25-hydroxyvitamin D [25(OH)D] with the use of high-performance liquid chromatography-mass spectrometry, assessed dietary vitamin D intake with the use of 7-d dietary records, and created a vitamin D-synthesis genetic risk score (GRS) at baseline (1991-1995) in a cohort of 1182 Swedish men (mean age: 71 y). In a maximum of 18 y (median: 12 y) of follow-up, 116 men developed Alzheimer disease, 64 men developed vascular dementia, and 250 men developed all-cause dementia. An additional 80 men declined in cognitive function as assessed with the use of the Mini-Mental State Examination. Adjusted HRs and...

PLOS ONE, 2017

Abdominal obesity is a key contributor of metabolic disease. Recent trials suggest that dietary f... more Abdominal obesity is a key contributor of metabolic disease. Recent trials suggest that dietary fat quality affects abdominal fat content, where palmitic acid and linoleic acid influence abdominal obesity differently, while effects of n-3 polyunsaturated fatty acids are less studied. Also, fatty acid desaturation may be altered in abdominal obesity. We aimed to investigate cross-sectional associations of serum fatty acids and desaturases with abdominal obesity prevalence in a population-based cohort study. Serum cholesteryl ester fatty acids composition was measured by gas chromatography in 60-year old men (n = 1883) and women (n = 2015). Cross-sectional associations of fatty acids with abdominal obesity prevalence and anthropometric measures (e.g., sagittal abdominal diameter) were evaluated in multivariable-adjusted logistic and linear regression models, respectively. Similar models were employed to investigate relations between desaturase activities (estimated by fatty acid ratios) and abdominal obesity. In logistic regression analyses, palmitic acid, stearoyl-CoA-desaturase and Δ6-desaturase indices were associated with abdominal obesity; multivariable-adjusted odds ratios (95% confidence intervals) for highest versus lowest quartiles were 1.45 (1.19-1.76), 4.06 (3.27-5.05), and 3.07 (2.51-3.75), respectively. Linoleic acid, α-linolenic acid, docohexaenoic acid, and Δ5-desaturase were inversely associated with abdominal obesity; multivariable-adjusted odds ratios (95% confidence intervals): 0.39 (0.32-0.48), 0.74 (0.61-0.89), 0.76 (0.62-0.93), and 0.40 (0.33-0.49), respectively. Eicosapentaenoic acid was not associated with abdominal obesity. Similar results were obtained from linear regression models evaluating associations with different anthropometric measures. Sex-specific and linear associations were mainly observed for n3-polyunsaturated fatty acids, while associations of the other exposures were generally non-linear and similar across sexes. In accordance with findings from short-term trials, abdominal obesity was more common among individuals with relatively high proportions of palmitic acid, whilst the PLOS ONE |

Kostmonster och risk for utveckling av demenssjukdom : en 12 ars uppfoljning av 70 ariga man

Journal of Renal Nutrition, 2016

Clinical kidney journal, 2015

Both albuminuria and kidney dysfunction may affect circadian blood pressure (BP) rhythm, while ex... more Both albuminuria and kidney dysfunction may affect circadian blood pressure (BP) rhythm, while exacerbating each other's effects. We investigated associations and interactions of these two risk factors with circadian BP rhythm variation and non-dipper pattern progression in community-dwelling older men. This was a cross-sectional and longitudinal analyses in the third and fourth cycles of the Uppsala Longitudinal Study of Adult Men, including 1051 men (age 71 years) with assessments on urinary albumin excretion rate (UAER), 24-h ambulatory BP monitoring (ABPM) and cystatin-C-estimated glomerular filtration rate (eGFR). Of these, 574 men attended re-examination after 6 years. Study outcomes were ABMP changes and non-dipping BP pattern (prevalence and progression). UAER associated with circadian BP rhythm both cross-sectionally and longitudinally. Longitudinally, significant interactions were observed between UAER and kidney dysfunction (eGFR < 60 mL/min/1.73 m(2)) in its assoc...

Journal of Applied Physiology, 2015

The delivery of efficient nonpharmacological treatment to prevent the loss of muscle mass in olde... more The delivery of efficient nonpharmacological treatment to prevent the loss of muscle mass in older adults is a major challenge, and information on the combined effects of training and diet is particularly important. Here we aimed to evaluate the effects of 24 wk of resistance training combined with a healthy dietary approach (n-6/n-3 ratio < 2) in a population of healthy and physically active older women (65-70 years). The three-armed randomized controlled trial included a resistance training + healthy diet group (RT-HD), a resistance training group (RT), and controls (CON). All subjects included in the study were physically active and had low levels of serum inflammatory markers. In accordance with the dietary goals, the n-6/n-3 ratio dietary intake significantly decreased only in RT-HD by 42%. An increase in 1 repetition maximum in leg extension occurred in RT (+20.4%) and RT-HD (+20.8%), but not in CON. Interestingly, leg lean mass significantly increased only in RT-HD (+1.8%)...

The Journal of Clinical Endocrinology & Metabolism, 2015

Nephrology Dialysis Transplantation, 2013

Introduction and Aims: Albuminuria is an independent predictor of cardiovascular (CV) mortality, ... more Introduction and Aims: Albuminuria is an independent predictor of cardiovascular (CV) mortality, regardless of the presence of diabetes or hypertension. Still, only single urine samples are available in most previous studies and so far, there is no consensus of numbers urine samples needed for risk prediction. This study examined the impact of increasing numbers of urine samples at different albuminuria cutoff levels for prediction of long-term CV mortality. Methods: In a prospective cohort study from the population-based Nord-Trøndelag Health Study (HUNT), Norway, we followed 9,158 adults with known diabetes, treated hypertension or randomly selected for 13 years. Albumin-to-creatinine ratios (ACR) in 3 morning urine samples were available from each participant. Adjusted hazard ratios (HR) for CV mortality on increasing number of positive ACR at different ACR cutoffs were assessed in Cox survival analyses, and predictive performance of models based on Framingham variables plus 1 versus 3 ACRs was evaluated. Results: For levels above high-normal ACR range (i.e. cutoffs >1.0 mg/mmol), single urine sample was enough to demonstrate a significant association to CV mortality (HR 1.36; 95% CI, 1.13-1.64; P = 0.001) in the total sample. This applied to all subgroups for cutoff levels >2.7 mg/mmol. For lower levels, 2 or 3 urine samples were needed for significance. There was neither improvement in discrimination (C-statistics 0.822 vs. 0.822; P=0.65) or calibration using 3 compared to 1 ACR value, nor did reclassification improve CV risk prediction (Net Reclassification Improvement 0.007 (-0.01-0.02)). However, considering ACR cutoffs below the high albuminuria ("microalbuminuria") range, multiple ACR measurements might be superior. Conclusions: Single urine ACR measurement will, in most clinical situations, be sufficient for CV mortality risk evaluation, since additional urine samples only improved diagnostic accuracy marginally.

Nephrology Dialysis Transplantation, 2012

Background. Polyunsaturated fatty acids (PUFA) are essential nutrients with anti-inflammatory and... more Background. Polyunsaturated fatty acids (PUFA) are essential nutrients with anti-inflammatory and cardioprotective properties. We investigated the association of essential dietary PUFA intake, reflected by plasma fatty acid composition, with inflammation and mortality in dialysis patients. Methods. We recruited 222 Swedish dialysis subjects (39% women) with median age of 57 years and average 12 months of dialysis vintage. Plasma phospholipid PUFA were assessed by gas-liquid chromatography. Overall mortality was assessed after 18.4 (10th-90th percentiles: 2.3-60) months of follow-up. Results. Linoleic acid (LA), Mead acid (MA), α-linolenic acid (ALA) and long-chain n-3 PUFA (LC n-3; the sum of eicosapentaenoic, docosapentaenoic and docosahexaenoic acids) represented 19.7, 0.26, 0.26 and 7.64% of all fatty acids in plasma, respectively. This may reflect an adequate n-3 PUFA intake. LA was negatively (β = − 0.21, P = 0.004) but MA positively (β = 0.25, P < 0.001) associated with interleukin (IL)-6 in multivariate analyses. Neither ALA nor LC n-3 were independently associated with IL-6. During follow-up, 61 deaths and 115 kidney transplants occurred. Fully adjusted competing risk models showed that every percent increase in the proportion of plasma LA was associated with 12% reduction in mortality risk before transplantation (hazard ratio 0.88, 95% confidence interval 0.79-0.99). MA was directly associated with mortality. Neither ALA nor LC n-3 predicted outcome. Conclusions. The proportion of plasma phospholipid LA is inversely associated with IL-6 and all-cause mortality in Swedish dialysis patients. We raise the hypothesis that dialysis patients could benefit from increased intake of vegetable oils, the primary source of LA in the Western-type diet.

Journal of Internal Medicine, 2013

ObjectivesThe causes of the multiple metabolic disorders of individuals with chronic kidney disea... more ObjectivesThe causes of the multiple metabolic disorders of individuals with chronic kidney disease (CKD) are not fully known. We investigated the relationships between dietary fat quality, the metabolic syndrome (MetS), insulin sensitivity and inflammation in individuals with CKD.SubjectsTwo population‐based surveys were conducted in elderly Swedish individuals (aged 70 years) with serum cystatin C‐estimated glomerular filtration rate <60 mL min−1/1.73 m2: the Uppsala Longitudinal Study of Adult Men (ULSAM) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) surveys. The present population comprised 274 men and 187 subjects (63% women) from the ULSAM and PIVUS cohorts, respectively.DesignFactor analyses of serum fatty acids were used to evaluate dietary fat quality. Insulin sensitivity was measured by homeostasis model assessment of insulin resistance (IR) and, in ULSAM, also by euglycaemic clamp.ResultsFactor analyses generated two fatty acid pattern...

Food & Nutrition Research, 2012

Background: A healthy Nordic diet (ND), a diet based on foods originating from the Nordic countri... more Background: A healthy Nordic diet (ND), a diet based on foods originating from the Nordic countries, improves blood lipid profile and insulin sensitivity and lowers blood pressure and body weight in hypercholesterolemic subjects. Objective: To describe and compare food and nutrient composition of the ND in relation to the intake of a Swedish reference population (SRP) and the recommended intake (RI) and average requirement (AR), as described by the Nordic nutrition recommendations (NNR). Design: The analyses were based on an estimate of actual food and nutrient intake of 44 men and women (mean age 5398 years, BMI 2693), representing an intervention arm receiving ND for 6 weeks. Results: The main difference between ND and SRP was the higher intake of plant foods, fish, egg and vegetable fat and a lower intake of meat products, dairy products, sweets and desserts and alcoholic beverages during ND (pB0.001 for all food groups). Intake of cereals and seeds was similar between ND and SRP (p 0.3). The relative intake of protein, fat and carbohydrates during ND was in accordance with RI. Intake of all vitamins and minerals was above AR, whereas sodium intake was below RI. Conclusions: When compared with the food intake of an SRP, ND is primarily a plant-based diet. ND represents a balanced food intake that meets the current RI and AR of NNR 2004 and has a dietary pattern that is associated with decreased morbidity and mortality.

Experimental Gerontology, 2013