Kjetil Retterstøl

• Holven, Kirsten Bjørklund; Dahl, Tuva Børresdatter; Bålsrud, Pia; Christensen, Jacob Juel; Ottestad, Inger Olaug & Rundblad, Amanda [Show all 15 contributors for this article] (2026). Cetoleic acid rich fish oil increases plasma levels of eicosapentaenoic and docosapentaenoic acids in healthy volunteers: a double-blinded, randomised, controlled trial. British Journal of Nutrition. ISSN 0007-1145. p. 1–28. doi: 10.1017/S0007114526107958. Full text in Research Archive Show summary

  Intake of fish and supplementation with n-3 polyunsaturated fatty acids (PUFA) are associated with reduced incidence of cardiovascular disease (CVD). Cetoleic acid promotes n-3 PUFA generation in salmon and human HepG2 cells, but data in humans are scarce. To explore the effect of cetoleic acid on n-3 PUFA levels, we performed a double-blinded randomised controlled trial in healthy adults (37 females and 12 males) for four weeks. The participants were randomised to consume either capsules with mackerel oil, naturally rich in cetoleic acid, or a control oil, both with a similar concentration of n-3 PUFA. Clinicaltrials.gov (NCT04841044). Supplements with mackerel oil resulted in higher plasma levels of the n-3 PUFAs 20:4n-3 (Eicosatetraenoic acid) and 20:5n-3 (Eicosapentaenoic acid) as compared with those receiving control oil. In addition, those who received the cetoleic-rich capsules had higher levels of 20:4n-3 in the RBC membrane and a decrease in expression of elongation of very long chain fatty acids protein 5 in peripheral blood mononuclear cells. We found no differences in lipid, glucose or C-reactive protein between the two treatment groups, consisting of healthy subjects. Our data suggests that supplementation with cetoleic-rich mackerel oil may result in increased levels of certain n-3 PUFAs. Further studies should include patients with or at risk for metabolic and CVD.

• Langslet, Gisle; Kollstad, Synne; Jørstad, Øystein Kalsnes; Erke, Maja Gran; Retterstøl, Kjetil & Holven, Kirsten Bjørklund (2026). Retinal findings in familial hypercholesterolemia: An exploratory case-control study. Atherosclerosis Plus. ISSN 2667-0909. 65. doi: 10.1016/j.athplu.2026.100571. Full text in Research Archive
• Olsen, Thomas; Elshorbagy, Amany; Tore, Elena C.; Bastani, Nasser Ezzatkhah; Stolt, Emma Theresia Kjelland & Blokland, Gabriëlla A.M. [Show all 16 contributors for this article] (2026). Higher plasma serine levels are associated with favorable values of metabolic health markers among middle-aged and older adults in The Maastricht Study. GeroScience. ISSN 2509-2715. doi: 10.1007/s11357-026-02237-4. Full text in Research Archive Show summary

  Laboratory studies indicate a mechanistic role for serine in the metabolic benefits induced by dietary restriction of methionine and cysteine. To investigate the association of plasma serine with metabolic health markers in humans, we conducted a cross-sectional analysis of a subset of data from The Maastricht Study (n = 1199). Linear regression analyses (adjusted for confounding variables) were conducted to investigate whether plasma serine is associated with markers of lipid metabolism, glucose homeostasis, and body composition. Interaction analyses were conducted to investigate whether sex, diabetes status, and plasma total cysteine modify the association of serine with metabolic markers. Correlations between dietary intake of sulfur amino acids and plasma amino acids, including methionine and total cysteine, were also investigated. Elevated plasma serine was associated with favorable changes in markers of lipid metabolism (triglycerides, total cholesterol, and indices of multiple fatty acid desaturases), glucose homeostasis (insulin resistance and glucose tolerance), fat utilization (β-hydroxybutyrate, acetoacetate, and acetone), and body composition (visceral and subcutaneous adipose depots, liver fat, and body mass index). Some associations were stronger in males than in females and in individuals with prediabetes and diabetes than in those without diabetes. Associations of plasma serine with body mass index, total fat mass, total lean mass, and subcutaneous adipose tissue weakened as plasma cysteine increased. Combined methionine and cysteine intake was inversely associated with plasma serine. Findings suggest that plasma serine is strongly associated with improved metabolic health in humans. Additional studies are required to confirm whether the associations are causal.

• Bålsrud, Pia; Ulven, Stine Marie; Hjartåker, Anette; Ottestad, Inger Olaug; Retterstøl, Kjetil & Schwab, Ursula [Show all 9 contributors for this article] (2026). Association between dietary protein intake and frailty index among home-dwelling older adults; an 8-year follow-up study. The Journal of Nutrition, Health & Aging. ISSN 1279-7707. 30(6). doi: 10.1016/j.jnha.2026.100850. Full text in Research Archive
• Klevmoen, Marianne; Lennep, Jeanine Roeters van; Bogsrud, Martin Prøven; Vesterbekkmo, Elisabeth Kleivhaug; Pedersen, Eva Ringdal & Hovland, Anders Wilhelm [Show all 14 contributors for this article] (2026). Extensive pregnancy-related off-treatment time in women with familial hypercholesterolaemia. Atherosclerosis. ISSN 0021-9150. 415. doi: 10.1016/j.atherosclerosis.2026.120668. Full text in Research Archive Show summary

  Background and aims: Women with familial hypercholesterolaemia (FH) lose substantial treatment time during their reproductive years as most lipid-lowering therapies are contraindicated from the preconception through the end of breastfeeding. We examined the duration of real-life pregnancy-related off-treatment time in 27 women with FH in Norway. Methods: Women with FH in Norway who had completed the ongoing FH-FEMINA study (ClinicalTrials.gov ID NCT05367310) were included. Women were followed from 36th week of gestation and until one year after delivery or until end of breastfeeding. Information on use of medication before, during and after the current and previous pregnancies was collected. Pregnancy-related off-treatment time was calculated from discontinuation of lipid-lowering therapy when planning pregnancy, throughout pregnancy, and after delivery. Results: The total duration of pregnancy-related off-treatment time after all childbirths (median 1, range 1-3) per woman was a median of 2.9 years (25th-75th percentile; 1.6-4.0), ranging from 0.8 to 12 years. The pregnancy itself accounted for median of 42.1% of the pregnancy-related off-treatment time, whereas the time before and after pregnancy accounted for a median of 57.9% (range 11.4% to 91.2%). When including untreated years in childhood and/or prior to diagnosis, the lifelong off-treatment time represented a median of 66.3% (range 41.9 to 100%) of lifetime without treatment. Conclusion: Early diagnosis and initiation of treatment is essential in girls with FH to compensate for pregnancy-related off-treatment time later in life. To minimize these pregnancy-related off-treatment periods, healthcare professionals should support women with FH to resume lipid-lowering therapy immediately after breastfeeding and between pregnancies. In addition, more knowledge on the potential effects of statin use during pregnancy and breastfeeding on maternal and offspring health is urgently needed.

• Pedersen, Jonas; Hedegaard, Berit Storgaard; Schmidt, Erik Berg; Dahm, Christina C.; Holven, Kirsten Bjørklund & Retterstøl, Kjetil [Show all 8 contributors for this article] (2025). Monounsaturated Fatty Acids in Cardiovascular Disease: Intake, Individual Types, and Content in Adipose Tissue as a Biomarker of Endogenous Exposure. Nutrients. 17(15). doi: 10.3390/nu17152509. Full text in Research Archive Show summary

  Unhealthy dietary patterns are a major modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD). International guidelines recommend reducing saturated fatty acid intake while increasing polyunsaturated and monounsaturated fatty acids (MUFAs) to mitigate cardiovascular risk. However, evidence regarding MUFAs and risk of ASCVD remains conflicting, with recent studies raising concern about a potential higher risk associated with MUFA intake. The aim of this narrative review is to provide an overview of current knowledge and gaps in the literature regarding MUFAs and the risk of ASCVD with a focus on intake, individual types, and content in adipose tissue as a biomarker of endogenous exposure. Main findings reveal that most studies have inappropriately combined all MUFAs together, despite individual MUFA types having different biological effects and showing varying correlations between dietary intake and adipose tissue content. Adipose tissue composition may serve as a biomarker of long-term MUFA exposure, reflecting cumulative intake over one to two years while minimizing biases inherent in dietary assessments. However, tissue levels reflect both dietary intake and endogenous synthesis, complicating interpretation. Importantly, the source of MUFAs appears critical, with plant-derived MUFAs potentially offering advantages over animal-derived sources. In conclusion, we suggest that future research should focus on individual MUFA types rather than treating them as a homogeneous group, investigate their specific dietary sources and associations with ASCVD risk, and use adipose tissue biomarkers to improve exposure assessment and clarify causal relationships while considering overall dietary patterns.

• Langslet, Gisle; Asprusten, Emil Andreas; Igland, Jannicke; Holven, Kirsten Bjørklund; Bogsrud, Martin Prøven & Retterstøl, Kjetil (2025). Cardiovascular disease and compliance with lipid-lowering therapy among young individuals with familial hypercholesterolemia in Norway – A register study. American Journal of Preventive Cardiology. 23. doi: 10.1016/j.ajpc.2025.101043. Full text in Research Archive Show summary

  Aims Investigation of cardiovascular disease (CVD), all-cause death and use of statins and ezetimibe among young Norwegian individuals with heterozygous Familial hypercholesterolemia (FH). Methods We included subjects with genetically verified FH born 1988–2008 and twenty controls per FH subject, with linkage to prescription data, hospitalization data and cause of death from national Norwegian health registries. Data on CHD and death during 2008–2018, and for dispensed prescriptions during 2004–2018, were collected. Results 1351 subjects with FH and 27,015 controls were included. Mean age (SD) at start of follow-up was 12.3 (5.4) years. There was one Coronary Heart Disease (CHD) event and 6 deaths in the FH-group and 3 CHD events and 53 deaths in the control group. CHD and all-cause death were non-significantly increased in the FH-group, hazard ratios (95 % confidence intervals) 6.68 (0.69–64.20) and 2.26 (0.98–5.28), respectively. None of the deaths in the FH-group were related to cardiovascular disease. 83 % of subjects with FH had been prescribed a statin, and 21 % ezetimibe. During the first year after the first prescription, 18.5 % of subjects did not refill their prescription within 180 days after the end date of the previous prescription. 69 % and 60 % of subjects with a prescription had >80 % of days covered with statins and ezetimibe, respectively. After 8 years, around 70 % of subjects were covered with statins. Conclusions Results suggest increased risk of CHD in FH relative to controls, but measures are imprecise because of low absolute risks. Compliance with lipid lowering therapy was moderate.

• Wisløff, Torbjørn; Mundal, Liv Jorunn; Igland, Jannicke; Svendsen, Karianne; Bogsrud, Martin Prøven & Kristiansen, Ivar Sønbø [Show all 7 contributors for this article] (2025). Ten-year costs of cardiovascular disease in genetically verified familial hypercholesterolaemia compared with age- and sex-matched controls. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. doi: 10.1093/eurjpc/zwaf592. Full text in Research Archive Show summary

  Aims Available data on economic consequences of carrying an inherited familial hypercholesterolaemia (FH) genetic variant are sparse. This study aims to explore the hospital and pharmaceutical resource use and costs associated with cardiovascular disease (CVD) in patients with genetically verified FH compared with age- and sex-matched controls during the period 2010 through 2019. Methods and results We included 5585 individuals with genetically verified FH from the Norwegian Unit for Cardiac and Cardiovascular Genetics registry and 111 483 age- and sex-matched controls from the general Norwegian population. Resource use and costs associated with CVD were collected from the Norwegian Patient Registry, the Cause of Death Registry, and the Norwegian Prescription Database. We estimated costs in European euros (EUR, €) based on diagnosis-related group (DRG) cost weights and pharmaceutical drug prices (Norwegian kroner 1 = EUR 0.1015). During 2010–19, patients with FH had CVD-related costs of €3911 per person for hospital care and €6119 for pharmaceuticals compared with €1498 and €514 among controls, respectively. The 10-year costs per person of percutaneous coronary interventions were €561 for FH and €140 for controls. The costs of CVD prescription drugs doubled in the FH population during 2010–19, largely due to the introduction of proprotein convertase subtilisin/kexin Type 9 inhibitors. Costs for prescription drugs increased in both the FH and control populations (P = 0.002 for FH and P = 0.005 for controls), while costs decreased for hospital care (P = 0. 0069 for FH and P = 0. 0943 for controls). Conclusion Familial hypercholesterolaemia patients had about three times higher CVD-related hospital costs and more than 10 times higher pharmaceutical costs than age- and sex-matched controls during a 10-year follow-up. During the 10 years, costs for pharmaceuticals increased and costs for hospital decreased.

• Bogsrud, Martin Prøven; Stava, Tonje Talsnes; Berge, Knut Erik; Strøm, Thea Bismo; Retterstøl, Kjetil & Holven, Kirsten Bjørklund (2025). LDL-cholesterol in newborns and children with genetically verified familial hypercholesterolaemia: implications for cholesterol-based screening. European Heart Journal. ISSN 0195-668X. 46(48), p. 5261–5269. doi: 10.1093/eurheartj/ehaf815. Full text in Research Archive Show summary

  Background and Aims: Cholesterol screening in children, with subsequent genetic testing of top percentile, has been suggested as an efficient universal screening approach in familial hypercholesterolaemia (FH). The potential cholesterol-based screening efficacy was investigated in a national genetically based screening programme. Methods: Data were from the Norwegian national family cascade screening programme in FH children from 1998 to 2023. Cholesterol levels [umbilical cord in newborns (n = 113) and venous blood in children 1–12 years old (n = 1346)] in variant positive and variant negative children were compared. Results: LDL cholesterol (LDL-C) was higher in FH newborns vs non-FH newborns [1.22 (.48) vs .68 (.32) mmol/L, P < .001], but overlapped widely. Cut-off levels corresponding to the 95th and 85th percentile would only identify 55.7% and 75.4% of newborns with FH, respectively. Screening efficacy in newborns did not differ in subgroups: boys and girls, null and non-null variants, variant gene, and neither for total cholesterol nor for non-HDL cholesterol. In all other age groups (from 1 to 12 years), LDL-C discriminated highly between mutation FH and non-FH children. Cut-off levels corresponding to 95th and 85th percentile of LDL-C would identify 88.4% and 94.1% of 1–12-year-old children with FH, respectively. Conclusions: Previous studies investigating lipid or genetic screening approaches for FH have limitations of only performing genetic testing in children with high LDL-C levels. The present study is the first to show the true LDL-C overlap in children with FH vs non-FH by utilizing unique data from a national family cascade screening programme. Cholesterol-based screening approaches for FH only seem feasible from 1 year of age onward.

• Melnes, Torunn; Bogsrud, Martin Prøven; Christensen, Jacob J.; Rundblad, Amanda; Retterstøl, Kjetil & Narverud, Ingunn [Show all 10 contributors for this article] (2025). LDL cholesterol burden in elderly patients with familial hypercholesterolemia: Insights from real-world data. American Journal of Preventive Cardiology. 22. doi: 10.1016/j.ajpc.2025.100986. Full text in Research Archive Show summary

  Background and aims Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) and increased risk of premature coronary heart disease (CHD). While current LDL-C levels usually guides therapy, the cumulative exposure to LDL-C (the LDL-C burden) is suggested to offer a more precise estimate of cardiovascular risk in people with FH. Therefore, using real-world data, this study aimed to estimate the LDL-C burden at different ages in elderly FH patients with and without CHD, and to assess the LDL-C burden at CHD onset. Methods Data was retrospectively collected from the medical records of elderly (>60 years) FH patients at the Lipid Clinic in Oslo. The LDL-C burden (mM-years) was estimated based on repeated LDL-C measurements and information on lipid-lowering medication. Time-weighted average (TWA) LDL-C was calculated as LDL-C burden divided by years. Results We included 112 FH patients, of which 55 (49 %) had experienced at least one CHD-event, and 58 (52 %) were females. Median age at first and last visit were 50 years and 68 years, respectively, with a median of 9 (range; 2–14) available LDL-C measurements. Subjects with CHD had higher LDL-C burden at all ages tested (45, 50 and 60 years) compared with the non-CHD group (p < 0.01, also after adjusting for sex), and had higher TWA LDL-C before treatment at the Lipid Clinic (p = 0.004), but not during follow-up (p = 0.6). There were no sex differences in LDL-C burden at all ages tested, also after adjusting for CHD (p > 0.1). However, women had higher TWA LDL-C during follow-up at the Lipid Clinic (p = 0.01). Median LDL-C burden at CHD onset was 352 mM-years; numerically lower in women than in men (320 vs. 357 mM-years, respectively. p = 0.1). Conclusion Elderly FH patients with CHD had higher estimated LDL-C burden compared with FH patients without CHD, due to higher burden prior to treatment, highlighting the importance of early detection and treatment.

• Arnesen, Erik Kristoffer; Christensen, Jacob J.; Laake, Ida; Carlsen, Monica Hauger; Veierød, Marit Bragelien & Retterstøl, Kjetil (2025). Low-fat and whole milk consumption in relation to cardiovascular disease–related and all-cause mortality: a prospective cohort study in 3 Norwegian counties. American Journal of Clinical Nutrition. ISSN 0002-9165. 122(4), p. 1075–1085. doi: 10.1016/j.ajcnut.2025.07.035. Full text in Research Archive Show summary

  Background The impact of milk consumption on cardiovascular disease (CVD) risk or mortality is unclear, and specific comparisons between types of milk are scarce. Objectives We aimed to investigate the associations between milk consumption, measured in a large Norwegian cohort in 3 counties during 1974–1988, and CVD–related mortality and all-cause mortality and to compare the associations between whole (full-fat) and low-fat milk. Methods This population-based, prospective cohort study included adults invited to repeated health screenings in the Norwegian Counties Study (>80% attendance). Dietary intake was assessed from food frequency questionnaires at each screening in 1974–1988. Cox regression analysis was used to estimate hazard ratios (HRs) with 95% CIs for the associations between milk intake (assessed as cumulative mean intake from repeated questionnaires) and risk of death from all CVD, ischemic heart disease (IHD), acute myocardial infarction (AMI), and all causes. Results Among 73,860 participants included in this study (mean age: 41.2 years at baseline; 49% females), 26,393 deaths occurred (8590 from CVD, 4372 from IHD, and 3047 from AMI) during a median follow-up of 33 y. Comparing the highest with the lowest quintile of overall milk intake, the HR was 1.12 (95% CI: 1.03, 1.21) for CVD-related mortality and 1.22 (95% CI: 1.16, 1.28) for all-cause mortality. For whole milk, high compared with no intake was positively associated with CVD (HR: 1.07; 95% CI: 0.99, 1.16), IHD (HR: 1.13; 95% CI: 1.01, 1.27), and all-cause mortality (HR: 1.15; 95% CI: 1.10, 1.21). Compared with whole milk, low-fat milk intake was associated with lower CVD-related, IHD-related, AMI-related, and all-cause mortality. The associations were attenuated in analyses considering only baseline intakes. Conclusions In this cohort with high milk consumption, whole milk is associated with higher CVD and all-cause mortality, whereas low-fat milk is not. Low-fat milk may be associated with lower risks than whole milk.

• Christensen, Jacob J; Holven, Kirsten Bjørklund; Bogsrud, Martin Prøven; Retterstøl, Kjetil; Lennep, Jeanine E Roeters van & Michelsen, Trond Melbye [Show all 8 contributors for this article] (2025). Statin use in pregnancy and risk of congenital malformations: a Norwegian nationwide study. European Heart Journal. ISSN 0195-668X. 47(3), p. 318–327. doi: 10.1093/eurheartj/ehaf592. Full text in Research Archive Show summary

  Background and Aims Statins and other lipid-modifying agents (LMAs) have traditionally been contraindicated during pregnancy due to concerns about harmful fetal effects; however, the risks associated with exposure to statins and other LMAs in human pregnancies remain unclear. Therefore, this study aimed to examine the associations between statin and LMA exposure in pregnancy and congenital malformations in offspring, while updating a 2022 meta-analysis with the results from the present study. Methods National registry data were linked for all pregnant women in Norway in 2005–18. Associations between first-trimester statin prescription fills and congenital malformations were estimated with mixed-effects logistic regression, adjusting for age, parity, pre-pregnancy folate use, smoking in early pregnancy, comorbidity, and co-medication. Meta-analyses were performed with the generic inverse–variance method and random-effects model. Results Congenital malformations occurred among 34 755 out of 803 830 (4.3%) statin non-exposed pregnancies, 74 out of 1255 (5.9%) statin-discontinuer pregnancies, and 19 out of 283 (6.7%) statin-exposed pregnancies. Adjusted odds ratios (ORs) for exposed vs non-exposed pregnancies were 1.30 [95% confidence interval (CI) .81–2.09] for any, 1.15 (.61–2.19) for major, and 1.47 (.75–2.89) for minor malformations. In analyses of exposed vs discontinuer pregnancies, there were no associations between statin exposure and any (adjusted OR 1.01, 95% CI .59–1.72), major (1.08, .52–2.25), or minor malformations (.94, .44–2.00). Results were similar across sensitivity analyses. There was also no association between any LMA exposure and heart malformations (adjusted OR 1.22, 95% CI .50–3.01). The updated meta-analysis suggested no increased risk of major (adjusted OR 1.06, 95% CI .86–1.31) or heart malformations (1.24, 95% CI .94–1.64). Conclusions In this large, nationwide study and updated meta-analysis, no significant association was observed between first-trimester exposure to statins or other LMAs and congenital malformations. Although limited power may have prevented detection of weak but clinically relevant associations, the findings do not support a strong or independent association between statin exposure in pregnancy and congenital malformations.

• Svendsen, Karianne; Christensen, Jacob J.; Igland, Jannicke; Krogh, Henriette Walaas; Mundal, Liv Jorunn & Jacobs, David R. [Show all 9 contributors for this article] (2025). Risk of adverse pregnancy outcomes and impact of statin use in pregnant women with familial hypercholesterolemia. Atherosclerosis. ISSN 0021-9150. 408, p. 1–8. doi: 10.1016/j.atherosclerosis.2025.120442. Full text in Research Archive Show summary

  Background and aims Sparse data exist on the risk of adverse pregnancy outcomes in women with familial hypercholesterolemia (FH). We investigated associations between FH and adverse pregnancy outcomes, and between statin exposure in pregnancy and adverse pregnancy outcomes among women with FH. Methods We studied 3869 pregnancies among 1869 women with genetically-proven FH and 68225 pregnancies among 33661 women from the general population. Data on adverse pregnancy outcomes were obtained during 1967–2018 from the Medical Birth Registry of Norway. Data on pharmacy-dispensed statins were obtained from the Norwegian prescription database (2004–2018) in 1051 women with FH. Associations were presented as odds ratio (OR) with 95 % CI from logistic regression adjusted for mother's age, parity, and offspring's birth year. Results Women with FH had a higher risk of preeclampsia (OR 1.21 [1.00–1.46]), but lower risk for gestational diabetes (OR 0.58 [0.36–0.92]) and intrapartum hemorrhage during delivery (OR 0.81 [0.71–0.92]) compared to controls. No excess risk of adverse pregnancy outcomes in offspring was observed for FH. Among women with FH, statin exposure (mainly in the first trimester) may be associated with higher risk of low birth weight in offspring born at term (OR 2.42 [0.51, 11.45]). Conclusions Women with FH had lower risk of gestational diabetes and intrapartum hemorrhage, but a higher risk of preeclampsia compared to controls. No adverse birth outcomes were observed for offspring of mothers with FH, but the association between statin exposure in pregnant women with FH and low birth weight in offspring warrants further study.

• Røstad-Tollefsen, Helen Kathrine; Venås, Benedicte Hagen; Kolset, Svein Olav; Retterstøl, Kjetil; Havdal, Hanne Hennig & Nordstrøm, Marianne (2025). External Factors Influencing the Motivation and Performance of Staff in Their Nutritional Work With Adults With Intellectual Disabilities. JARID: Journal of applied research in intellectual disabilities. ISSN 1360-2322. 38(1). doi: 10.1111/jar.70002. Full text in Research Archive Show summary

  Background Staff working in municipal care homes with adults with intellectual disabilities impact their diet significantly. Aim To explore how external factors influence staff's motivation and performance of nutritional work with these residents. Method Semi-structured qualitative interviews with 11 staff using systematic text condensation for analysis. Results Five main themes were revealed: Need for the implementation of the official nutritional guidelines, lack of nutritional skills and knowledge, prioritisation of nutritional work tasks, staff's ethical dilemmas with the different legislations and management anchoring and collaboration. Conclusions Implementing systematic nutritional routines and clarifying nutritional work in practice were emphasised to promote continuity and better cooperation among the staff. This, and the need for increased nutritional competence in the municipality organisation, adequate framework conditions for nutritional work and practical and pedagogical measures for nutritional tasks, were crucial factors for staff's motivation, performance, consistency and equality in nutritional practice.

• Westbye, Alexander Bauer; Dizdarevic, Lili Leko; Dahl, Sandra Rinne; Asprusten, Emil Andreas; Bliksrud, Yngve Thomas & Lövgren-Sandblom, Anita [Show all 9 contributors for this article] (2025). A sterol panel for rare lipid disorders: sitosterolemia, cerebrotendinous xanthomatosis and Smith-Lemli-Opitz syndrome. Journal of Lipid Research. ISSN 0022-2275. 66(1). doi: 10.1016/j.jlr.2024.100698. Full text in Research Archive Show summary

  Disease-specific sterols accumulate in the blood of patients with several rare lipid disorders. Biochemical measurement of these sterols is important for correct diagnosis and sometimes monitoring of treatment. Existing methods to measure sterols in blood, particularly plant sterols, are often laborious and time consuming. Partly as a result, clinical access to sterol measurements is limited in many parts of the world. A simple and rapid method to extract free sterols from human serum and quantitate their concentration using isotope-dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) without derivatization was developed. The method was designed to be compatible with routine workflows (e.g., 96-well format) in a clinical lab and extensively validated. Serum from at least 125 controls were analyzed and used to estimate the upper reference limits for sitosterol, campesterol, stigmasterol, desmosterol, 7-dehydrocholesterol (7DHC), lathosterol, and cholestanol. Serum from patients with the rare lipid disorders sitosterolemia (n = 7), Smith-Lemli-Opitz syndrome (SLOS; n = 1), and cerebrotendinous xanthomatosis (CTX; n = 1) were analyzed. All seven sitosterolemia patients had greatly elevated levels of free plant sterols (sitosterol, campesterol, and stigmasterol) compared to the controls. The SLOS serum contained massively increased concentrations of 7DHC. CTX serum contained greatly increased concentrations of cholestanol, as well as 7DHC and lathosterol. Spiking experiments indicated that the method is likely also useful for the diagnosis of desmosterolosis and lathosterolosis. The reported method is a relatively simple and fast LC-MS/MS method capable of quantitating diagnostically important sterols and differentiated patients with three rare lipid disorders from controls.

• Aaseth, Jan; Retterstøl, Kjetil; Rootwelt, Helge & Farup, Per Grønaas (2025). Reduction in Remnant Cholesterol in Obese Individuals After Bariatric Surgery with Gastric Bypass or Sleeve Gastrectomy. Nutrients. 17(1). doi: 10.3390/nu17010189. Full text in Research Archive Show summary

  Background: The effectiveness of bariatric surgery in reducing remnant cholesterol (RC) levels, particularly when obesity is accompanied by elevated glycated hemoglobin (HbA1c), is insufficiently investigated. In this study, we aimed to examine the impacts of two common bariatric procedures, Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), as regards their effects on RC and HbA1c levels. Methods: Adult morbidly obese subjects were included and assigned to receive either RYGB or SG. The levels of RC and HbA1c were determined 6 and 12 months after surgery and compared to preoperative levels to assess the efficacy of these surgical methods. In the statistical evaluation of covariations between RC and other biomarkers, previously determined C-reactive protein (CRP), triglycerides, apolipoprotein B, apolipoprotein A1, and low- and high-density lipoprotein cholesterol 6 and 12 months after surgery were included. A linear mixed regression model for repeated analyses was used. Results: The RC levels were markedly reduced both after RYGB and SG but without significant differences between the RYGB and the SG surgery. Furthermore, the RC values were strongly associated with the levels of CRP and HbA1c. Conclusions: A significant lowering of RC values after bariatric surgery appeared paralleled by concomitant reductions in HbA1c values and CRP levels. Together, these effects lead to a lower risk of cardiovascular disease.

• Olsen, Thomas; Stolt, Emma Theresia Kjelland; Øvrebø, Bente; Elshorbagy, Amany; Tore, Elena C. & Lee-Ødegård, Sindre [Show all 20 contributors for this article] (2024). Dietary sulfur amino acid restriction in humans with overweight and obesity: a translational randomized controlled trial. Journal of Translational Medicine. 22(40). doi: 10.1186/s12967-023-04833-w. Full text in Research Archive Show summary

  Background Dietary sulfur amino acid restriction (SAAR) improves metabolic health in animals. In this study, we investigated the effect of dietary SAAR on body weight, body composition, resting metabolic rate, gene expression profiles in white adipose tissue (WAT), and an extensive blood biomarker profile in humans with overweight or obesity. Methods N = 59 participants with overweight or obesity (73% women) were randomized stratified by sex to an 8-week plant-based dietary intervention low (~ 2 g/day, SAAR) or high (~ 5.6 g/day, control group) in sulfur amino acids. The diets were provided in full to the participants, and both investigators and participants were blinded to the intervention. Outcome analyses were performed using linear mixed model regression adjusted for baseline values of the outcome and sex. Results SAAR led to a ~ 20% greater weight loss compared to controls (β 95% CI − 1.14 (− 2.04, − 0.25) kg, p = 0.013). Despite greater weight loss, resting metabolic rate remained similar between groups. Furthermore, SAAR decreased serum leptin, and increased ketone bodies compared to controls. In WAT, 20 genes were upregulated whereas 24 genes were downregulated (FDR < 5%) in the SAAR group compared to controls. Generally applicable gene set enrichment analyses revealed that processes associated with ribosomes were upregulated, whereas processes related to structural components were downregulated. Conclusion Our study shows that SAAR leads to greater weight loss, decreased leptin and increased ketone bodies compared to controls. Further research on SAAR is needed to investigate the therapeutic potential for metabolic conditions in humans. Trial registration: ClinicalTrials.gov identifier: NCT04701346, registered Jan 8th 2021, https://www.clinicaltrials.gov/study/NCT04701346

• Jeevanathan, Janeni; Blom, Sigrid Marie; Olsen, Thomas; Holven, Kirsten Bjørklund; Arnesen, Erik Kristoffer & Trydal, Torleif [Show all 11 contributors for this article] (2024). Real-world impact of transitioning from one lipoprotein(a) assay to another in a clinical setting. American Journal of Preventive Cardiology. 19. doi: 10.1016/j.ajpc.2024.100726. Full text in Research Archive Show summary

  Background and aims: Different lipoprotein(a) [Lp(a)] assays may affect risk stratification of individuals and thus clinical decision-making. We aimed to investigate how transitioning between Lp(a) assays at a large central laboratory affected the proportion of individuals with Lp(a) result above clinical thresholds. Methods: We studied nationwide clinical laboratory data including 185,493 unique individuals (47.7 % women) aged 18-50 years with 272,463 Lp(a) measurements using Roche (2000-2009) and Siemens Lp(a) assay (2009-2019). Results: While the majority of individuals (66-75 %) had low levels of Lp(a) (<30 mg/dL) independent of the assay used, the Roche assay detected 20 % more individuals with Lp(a) >50 mg/dL, 40 % more individuals with Lp(a) >100 mg/dL and 80 % more individuals with Lp(a) >180 mg/dL than the currently used Siemens assay, likely due to calibration differences. Conclusion: Transitioning from one Lp(a) immunoassay to another had significant impact on Lp(a) results, particularly in individuals approaching clinically relevant Lp(a) thresholds.

• Olsen, Thomas; Vinknes, Kathrine Jørgensen; Barvíková, Kristýna; Stolt, Emma Theresia Kjelland; Lee-Ødegård, Sindre & Troensegaard, Hannibal [Show all 18 contributors for this article] (2024). Dietary sulfur amino acid restriction in humans with overweight and obesity: Evidence of an altered plasma and urine sulfurome, and a novel metabolic signature that correlates with loss of fat mass and adipose tissue gene expression. Redox Biology. 73. doi: 10.1016/j.redox.2024.103192. Full text in Research Archive Show summary

  Background In animals, dietary sulfur amino acid restriction (SAAR) improves metabolic health, possibly mediated by altering sulfur amino acid metabolism and enhanced anti-obesogenic processes in adipose tissue. Aim To assess the effects of SAAR over time on the plasma and urine SAA-related metabolites (sulfurome) in humans with overweight and obesity, and explore whether such changes were associated with body weight, body fat and adipose tissue gene expression. Methods Fifty-nine subjects were randomly allocated to SAAR (∼2 g SAA, n = 31) or a control diet (∼5.6 g SAA, n = 28) consisting of plant-based whole-foods and supplemented with capsules to titrate contents of SAA. Sulfurome metabolites in plasma and urine at baseline, 4 and 8 weeks were measured using HPLC and LC-MS/MS. mRNA-sequencing of subcutaneous white adipose tissue (scWAT) was performed to assess changes in gene expression. Data were analyzed with mixed model regression. Principal component analyses (PCA) were performed on the sulfurome data to identify potential signatures characterizing the response to SAAR. Results SAAR led to marked decrease of the main urinary excretion product sulfate (p < 0.001) and plasma and/or 24-h urine concentrations of cystathionine, sulfite, thiosulfate, H2S, hypotaurine and taurine. PCA revealed a distinct metabolic signature related to decreased transsulfuration and H2S catabolism that predicted greater weight loss and android fat mass loss in SAAR vs. controls (all pinteraction < 0.05). This signature correlated positively with scWAT expression of genes in the tricarboxylic acid cycle, electron transport and β-oxidation (FDR = 0.02). Conclusion SAAR leads to distinct alterations of the plasma and urine sulfurome in humans, and predicted increased loss of weight and android fat mass, and adipose tissue lipolytic gene expression in scWAT. Our data suggest that SAA are linked to obesogenic processes and that SAAR may be useful for obesity and related disorders.

• Melnes, Torunn; Bogsrud, Martin Prøven; Christensen, Jacob Juel; Rundblad, Amanda; Narverud, Ingunn & Retterstøl, Kjetil [Show all 10 contributors for this article] (2024). Gene expression profiling in elderly patients with familial hypercholesterolemia with and without coronary heart disease. Atherosclerosis. ISSN 0021-9150. 392. doi: 10.1016/j.atherosclerosis.2024.117507. Full text in Research Archive Show summary

  Background and aims Elderly familial hypercholesterolemia (FH) patients are at high risk of coronary heart disease (CHD) due to high cholesterol burden and late onset of effective cholesterol-lowering therapies. A subset of these individuals remains free from any CHD event, indicating the potential presence of protective factors. Identifying possible cardioprotective gene expression profiles could contribute to our understanding of CHD prevention and future preventive treatment. Therefore, this study aimed to investigate gene expression profiles in elderly event-free FH patients. Methods Expression of 773 genes was analysed using the Nanostring Metabolic Pathways Panel, in peripheral blood mononuclear cells (PBMCs) from FH patients ≥65 years without CHD (FH event-free, n = 44) and with CHD (FH CHD, n = 39), and from healthy controls ≥70 years (n = 39). Results None of the genes were differentially expressed between FH patients with and without CHD after adjusting for multiple testing. However, at nominal p < 0.05, we found 36 (5%) differentially expressed genes (DEGs) between the two FH groups, mainly related to lipid metabolism (e.g. higher expression of ABCA1 and ABCG1 in FH event-free) and immune responses (e.g. lower expression of STAT1 and STAT3 in FH event-free). When comparing FH patients to controls, the event-free group had fewer DEGs than the CHD group; 147 (19%) and 219 (28%) DEGs, respectively. Conclusions Elderly event-free FH patients displayed a different PBMC gene expression profile compared to FH patients with CHD. Differences in gene expression compared to healthy controls were more pronounced in the CHD group, indicating a less atherogenic gene expression profile in event-free individuals. Overall, identification of cardioprotective factors could lead to future therapeutic targets.

• Bålsrud, Pia; Ulven, Stine Marie; Ottestad, Inger; Retterstøl, Kjetil; Schwab, Ursula & Holven, Kirsten Bjørklund (2024). Association between inflammatory markers, body composition and frailty in home-dwelling elderly: an 8-year follow-up study. GeroScience. ISSN 2509-2715. 46, p. 5629–5641. doi: 10.1007/s11357-024-01279-w. Full text in Research Archive Show summary

  Frailty has been linked to inflammation and changes in body composition, but the findings are inconsistent. To explore this, we used the Frailty Index (FI) definition to (1) investigate the association between levels of inflammatory markers (baseline) and change in FI score after 8 years of follow-up and (2) investigate the longitudinal associations between inflammatory markers, body composition, and frailty. Home-dwelling elderly (≥ 70 years) were invited to participate in the study and re-invited to a follow-up visit 8 years later. This study includes a total of 133 participants. The inflammatory markers included were high-sensitive C-reactive protein (hs-CRP), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and glycoprotein acetyls (Gp-acetyls). We used the body composition markers fat mass, fat-free mass, and waist circumference. The FI score consisted of 38 variables. Additional clinical assessments such as blood pressure and body mass index (BMI), as well as information about daily medications, were collected at both visits. Linear regression model and Spearman’s rank correlation were used to investigate associations. We showed that the FI score increased after 8 years, and participants with higher hs-CRP levels at baseline had the largest change in the FI score. Changes in fat mass were significantly correlated with changes in hs-CRP and IL-6, and changes in waist circumference were significantly correlated with changes in TNF-α. The use of drugs increased during the 8 years of follow-up, which may have attenuated the associations between inflammation and frailty. However, elevated concentrations of hs-CRP in the elderly may be associated with an increased risk of frailty in subsequent years.

• Karlsson, Cecilia; Johnsen, Line Kristin; Greasley, Peter; Retterstøl, Kjetil; Hedberg, Jonatan & Hall, Martin [Show all 18 contributors for this article] (2024). Gastric Bypass vs Diet and Cardiovascular Risk Factors: A Nonrandomized Controlled Trial. JAMA Surgery. ISSN 2168-6254. 159(9), p. 971–980. doi: 10.1001/jamasurg.2024.2162. Full text in Research Archive Show summary

  Importance Roux-en-Y gastric bypass (RYGB) is associated with reduced cardiovascular (CV) risk factors, morbidity, and mortality. Whether these effects are specifically induced by the surgical procedure or the weight loss is unclear. Objective To compare 6-week changes in CV risk factors in patients with obesity undergoing matching caloric restriction and weight loss by RYGB or a very low-energy diet (VLED). Design, Setting, and Participants This nonrandomized controlled study (Impact of Body Weight, Low Calorie Diet, and Gastric Bypass on Drug Bioavailability, Cardiovascular Risk Factors, and Metabolic Biomarkers [COCKTAIL]) was conducted at a tertiary care obesity center in Norway. Participants were individuals with severe obesity preparing for RYGB or a VLED. Recruitment began February 26, 2015; the first patient visit was on March 18, 2015, and the last patient visit (9-week follow-up) was on August 9, 2017. Data were analyzed from April 30, 2021, through June 29, 2023. Interventions VLED alone for 6 weeks or VLED for 6 weeks after RYGB; both interventions were preceded by 3-week LED. Main Outcomes and Measures Between-group comparisons of 6-week changes in CV risk factors. Results Among 78 patients included in the analyses, the mean (SD) age was 47.5 (9.7) years; 51 (65%) were women, and 27 (35%) were men. Except for a slightly higher mean (SD) body mass index of 44.5 (6.2) in the RYGB group (n = 41) vs 41.9 (5.4) in the VLED group (n = 37), baseline demographic and clinical characteristics were similar between groups. Major atherogenic blood lipids (low-density lipoprotein cholesterol, non–high-density lipoprotein cholesterol, apolipoprotein B, lipoprotein[a]) were reduced after RYGB in comparison with VLED despite a similar fat mass loss. Mean between-group differences were −17.7 mg/dL (95% CI, −27.9 to −7.5), −17.4 mg/dL (95% CI, −29.8 to −5.0) mg/dL, −9.94 mg/dL (95% CI, −15.75 to −4.14), and geometric mean ratio was 0.55 U/L (95% CI, 0.42 to 0.72), respectively. Changes in glycemic control and blood pressure were similar between groups. Conclusions and Relevance This study found that clinically meaningful reductions in major atherogenic blood lipids were demonstrated after RYGB, indicating that RYGB may reduce CV risk independent of weight loss. Trial Registration ClinicalTrials.gov Identifier: NCT02386917

• Johansen, Anja Katrin; Bogsrud, Martin Prøven; Thoresen, Magne; Christensen, Jacob J.; Narverud, Ingunn & Langslet, Gisle [Show all 9 contributors for this article] (2024). Lipoprotein(a) in children and adolescents with genetically confirmed familial hypercholesterolemia followed up at a specialized lipid clinic. Atherosclerosis Plus. ISSN 2667-0909. 57, p. 13–18. doi: 10.1016/j.athplu.2024.06.002. Full text in Research Archive Show summary

  Background and aim Many children with an FH mutation also exhibit elevated lipoprotein(a) levels, which is an independent risk factor for atherosclerotic cardiovascular disease. Studies have reported higher levels of lipoprotein(a) in adult and middle-aged women than men. There is limited knowledge on the concentration and change of lipoprotein(a) levels in children with genetic FH, and therefore we investigated sex-differences in lipoprotein(a) level and change in lipoprotein(a) in girls and boys with genetically confirmed FH. Methods Medical records were reviewed retrospectively in 438 subjects with heterozygous FH that started follow-up below the age of 19 years at the Lipid Clinic, Oslo University Hospital in Norway, and of these we included 386 subjects with at least one Lp(a) measurement. Results Mean (SD) age at baseline was 13.8 (7.3) years and the age was similar between sexes. Girls had a higher lipoprotein(a) level than boys at baseline: median (25–75 percentile) 223 (108–487) vs. 154 (78–360) mg/L, respectively (p < 0.01). From baseline to follow-up measurement (mean [SD] 8.9 [6.1] years apart), the mean (95 % CI) absolute and percentage change in Lp(a) level in girls was 151.4 (54.9–247.8) mg/L and 44.8 (16.4–73.1) %, respectively, and in boys it was 66.8 (22.9–110.8) mg/L and 50.5 (8.8–92.3) %, respectively (both p > 0.05). Conclusions We found an increase in Lp(a) levels in children with genetic FH with age, and higher levels in girls than boys, which could impact risk assessment and future ASCVD. Further research is needed to elucidate whether subjects with FH could benefit from lipoprotein(a)-lowering therapies that are under current investigations.

• Løvheim, Eirin Brenna; Retterstøl, Kjetil; Narverud, Ingunn; Bogsrud, Martin Prøven; Halvorsen, Bente & Ueland, Thor [Show all 8 contributors for this article] (2024). Adherence to the Healthy Nordic Food Index is associated with reduced plasma levels of inflammatory markers in patients with heterozygous familial hypercholesterolemia. Atherosclerosis Plus. ISSN 2667-0909. 58, p. 38–45. doi: 10.1016/j.athplu.2024.10.003. Full text in Research Archive Show summary

  Background and aims Familial hypercholesterolemia (FH) is an inherited disease associated with hypercholesterolemia, and dietary treatment is part of the treatment. We aimed to assess the dietary pattern in relation to the Healthy Nordic Food Index (HNFI) in adults with and without heterozygous FH (HeFH), and to examine the associations between dietary quality and biomarkers related to cardiovascular disease in adults with HeFH. Methods We included 205 adults (≥18 years) with HeFH who received follow-up at the Lipid Clinic in Oslo and compared them to controls (n = 228). Dietary intake was assessed using a food frequency questionnaire and dietary quality was assessed using the HNFI. Blood samples were analysed for levels of blood lipids, plasma fatty acids (FAs), and markers of inflammation and platelet activation. Results The HeFH patients (median 60 years; 50.2 % female; 25.9 % in secondary prevention) had lower intake of total and saturated fat compared to controls (32.6 energy percent (E%) vs. 34.9 E%, and 9.6 E% vs 12.0 E%, respectively; p < 0.001 for both). In the HeFH patients, increasing dietary quality was associated with increased plasma levels of the n-3 polyunsaturated FAs (PUFAs) eicosapentaenoic acid and docosahexaenoic acid, and the n-6 PUFA linoleic acid, and lower plasma levels of the inflammatory cytokines Tumor Necrosis Factor and interleukin-6, and of the platelet-derived inflammatory cytokines Platelet Factor 4 and Neutrophil-Activating Peptide-2. Conclusion Norwegian patients with HeFH followed up at a Lipid Clinic eat healthier than controls. Adherence to a healthy dietary pattern is associated with higher plasma levels of n-3 and n-6 PUFA, and lower levels of inflammatory markers, including platelet markers. This may suggest that adherence to an overall healthy dietary pattern might be beneficial for HeFH patients independent of the cholesterol-lowering effect of the diet.

• Arnesen, Erik Kristoffer; Laake, Ida; Carlsen, Monica Hauger; Veierød, Marit Bragelien & Retterstøl, Kjetil (2024). Potato Consumption and All-Cause and Cardiovascular Disease Mortality – A Long-Term Follow-Up of a Norwegian Cohort. Journal of Nutrition. ISSN 0022-3166. 154(7), p. 2226–2235. doi: 10.1016/j.tjnut.2024.05.011. Full text in Research Archive Show summary

  Background Potatoes are a staple food in many traditional cuisines, yet their impact on long-term risk of cardiovascular disease (CVD) and mortality is unclear, hampering evidence-based dietary guidelines. Objectives This study aimed to examine the association between potato consumption and all-cause and CVD-specific death over a substantial follow-up period within a cohort predominantly consuming boiled potatoes. Methods Adults from 3 Norwegian counties were invited to 3 health screenings in 1974–1988 (>80% attendance). Dietary data were collected using semiquantitative food frequency questionnaires at each screening to categorize weekly potato consumption (≤6, 7–13, or ≥14 potatoes/wk) and calculate daily cumulative mean intakes (grams/day). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression to estimate HRs and 95% CIs for the association between potato consumption and risk of death from all causes, CVD, ischemic heart disease (IHD), and acute myocardial infarction (AMI). Results Among 77,297 participants with a mean baseline age of 41.1 y (range: 18.0–63.9 y), we observed 27,848 deaths, including 9072 deaths due to CVD, over a median follow-up of 33.5 y. Participants who consumed ≥14 potatoes/wk had a lower risk of all-cause death compared with those consuming ≤6 potatoes/wk (HR: 0.88; 95% CI: 0.84, 0.93). Potato consumption was associated with a minor, inverse risk of death due to CVD, IHD, and AMI. In continuous analyses of cumulative intakes, each 100 g/d increment was associated with 4% lower risk of death from all causes (HR: 0.96; 95% CI: 0.94, 0.98), CVD (HR: 0.96; 95% CI: 0.93, 0.99), IHD (HR: 0.96; 95% CI: 0.91, 1.00), and AMI (HR: 0.96, 95% CI: 0.91, 1.01). Conclusions In this cohort with a generally high consumption of predominantly boiled potatoes, we find modest, inverse associations between potato consumption and death from all causes, CVD, and IHD.

• Retterstøl, Kjetil & Rosqvist, Fredrik (2024). Fat and fatty acids – a scoping review for Nordic Nutrition Recommendations 2023. Food & Nutrition Research (FNR). ISSN 1654-6628. 68. doi: 10.29219/fnr.v68.9980. Full text in Research Archive Show summary

  Two de novo NNR2022 systematic reviews (SRs) as well as 21 qualified SRs (qSRs) were available. A literature search yielded an additional ~70 SRs, meta-analyses and biomarker papers. Diets lower in total fat are associated with reductions in body weight and blood pressure compared with diets higher in total fat in adults. Partial replacement of saturated fatty acid (SFA) with n-6 polyunsaturated fatty acid (PUFA) improves blood lipid profile, decreases the risk of cardiovascular disease (CVD), improves glucose-insulin homeostasis and may decrease the risk of total mortality. Long-chain n-3 PUFAs (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) decrease triglycerides and are associated with lower risk of CVD. Dietary PUFAs, both n-3 and n-6, may be associated with reduced risk of type 2 diabetes (T2D). There is inconclusive evidence to suggest that the type of dietary fat is associated with blood pressure, risk of hypertension or musculoskeletal health. Higher intake of total PUFA is associated with lower mortality from any cancer. Long-chain n-3 PUFA is associated with reduced risk of breast cancer, whereas biomarker levels of n-6 PUFA are associated with lower risk of any cancer. Intake of long-chain n-3 PUFA during pregnancy increases length of gestation and child birth weight and reduces the risk of preterm delivery, but there is inconclusive evidence to suggest that it may influence child neurodevelopment, growth or development of allergic disease. In studies with higher versus lower dietary cholesterol intake levels, total blood cholesterol increased or were unaffected by the dietary cholesterol, resulting in inconclusive results. Trans fatty acid (TFA), regardless of source, impairs blood lipid profile compared to unsaturated fat. In observational studies, TFA is positively associated with CVD and total mortality but whether associations differ by source is inconclusive. Ruminant TFA, as well as biomarker levels of odd-chain fatty acids, might be associated with lower risk of T2D.

• Arnesen, Erik Kristoffer; Laake, Ida; Veierød, Marit Bragelien & Retterstøl, Kjetil (2024). Saturated fatty acids and total and CVD mortality in Norway: a prospective cohort study with up to 45 years of follow-up. British Journal of Nutrition. ISSN 0007-1145. 132, p. 466–478. doi: 10.1017/S0007114524001351. Full text in Research Archive Show summary

  The contribution of dietary saturated fatty acids (SFA) to cardiovascular disease (CVD) and mortality remains debated after decades of research. Few previous studies had repeated dietary assessments and power to assess mortality. Evidence for individual SFA is limited. In this large population-based cohort study, we investigated associations between intake of total and individual SFA and risk of total and CVD mortality. Adult residents (mean 41·1 years at baseline) in three Norwegian counties were invited to repeated health screenings between 1974 and 1988 (> 80 % attendance). We calculated cumulative average intakes of macronutrients from semi-quantitative FFQ. Median (interquartile range) intake of SFA was 14·6 % (12·8–16·6 %) of total energy (E%). Hazard ratios (HR) and 95 % CI were estimated using multivariable Cox regression models to assess total, CVD, ischaemic heart disease (IHD) and acute myocardial infarction (AMI) mortality. Among 78 725 participants, 28 555 deaths occurred during a median follow-up of 33·5 years, with 9318 deaths due to CVD. Higher intake of SFA (replacing carbohydrates) was positively associated with all mortality endpoints, including total (HR per 5 E% increment, 1·18; 95 % CI 1·13, 1·23) and CVD mortality (1·16; 95 % CI 1·07, 1·25). Theoretical isoenergetic substitution of SFA with carbohydrates or MUFA was associated with lower risk. Of individual SFA, myristic (14:0) and palmitic acid (16:0) were positively associated with mortality. In summary, dietary SFA intake was strongly associated with higher total and CVD mortality in this long-term cohort study. This supports policies implemented to reduce SFA consumption in favour of carbohydrates and unsaturated fats.

• Angelsen, Madeleine Elisabeth; Johannessen, Emma; Retterstøl, Kjetil & Peleikis, Dawn Elisabeth (2024). Livsstilen til norske pasienter med en alvorlig psykisk lidelse. Norsk tidsskrift for ernæring (NTFE). ISSN 1503-5034. 22(1). doi: 10.18261/ntfe.22.1.2. Full text in Research Archive Show summary

  Bakgrunn: Pasienter med alvorlig psykisk lidelse har økt risiko for hjerte- og karsykdom, og modifiserbare risikofaktorer forekommer hyppig. Livsstilen til norske pasienter med alvorlig psykisk lidelse er lite studert. Materiale og metode: Pasienter med schizofreni eller bipolar lidelse ble rekruttert fra Asker distrikt-psykiatriske senter (DPS). Antropometri og blodprøver ble målt eller innhentet fra pasientjournaler. DIGIKOST (digitalt spørreskjema) målte kostholdsvaner, fysisk aktivitet og tobakk- og alkoholforbruk. Resultater: 42 pasienter, 23 menn og 19 kvinner ble inkludert. Gjennomsnittlig alder var henholdsvis 41 og 42 år. Mer enn halvparten hadde abdominal fedme. Forekomsten av metabolsk syndrom var 50 %. Kostholdet ble målt til lav/moderat kvalitet. Pasientene var lite fysisk aktive, og det var høy forekomst av røyking. Pasientene beskrev barrierer for sunn livsstil relatert til medisinering og innleggelse, og ønsket videre kostholdsveiledning. Fortolkning: Livsstilen til pasientene ved Asker DPS disponerte for økt risiko for hjerte- og karsykdom. Resultatene fra denne studien avdekket potensial for å redusere mortaliteten fra hjerte-og karsykdom hos pasienter med schizofreni eller bipolar lidelse.

• Olsen, Thomas; Elshorbagy, Amany; Stolt, Emma Theresia Kjelland; Åsberg, Anders; Zare, Hasse Khiabani & Bastani, Nasser Ezzatkhah [Show all 9 contributors for this article] (2024). Acute effects of oral mesna administration on the full amino acid profile and 3-methylhistidine: secondary results from the CYLOB dose-finding study. Amino Acids. ISSN 0939-4451. 56. doi: 10.1007/s00726-024-03398-2. Full text in Research Archive Show summary

  Plasma total cysteine (tCys) is strongly associated with fat mass in humans. Mesna lowers plasma tCys in a dose-dependent manner, but it is not known whether it interferes with metabolism of other amino acids or protein. In this Phase-1 study, we show that a single dose of mesna administered at 400, 800, 1200 or 1600 mg to 6–7 individuals per dose only slightly affects amino acid profiles, with increases in plasma valine across dose levels. There were no effects of mesna on 3-methylhistidine, a marker of protein breakdown.

• Tore, Elena C.; Adriaans, Bregje C.; Olsen, Thomas; Vinknes, Kathrine Jørgensen; Kooi, M. Eline & Elshorbagy, Amany [Show all 15 contributors for this article] (2024). Estimated stearoyl-CoA desaturase activity mediates the associations of total cysteine with adiposity: The Maastricht Study. Journal of Clinical Lipidology. ISSN 1933-2874. 19(2), p. 348–357. doi: 10.1016/j.jacl.2024.11.005. Full text in Research Archive Show summary

  Background Plasma sulfur amino acids (SAAs), particularly cysteine, are associated with obesity. One proposed mechanism is the altered regulation of the stearoyl-CoA desaturase (SCD) enzyme. Changes in the SCD enzyme activity have been linked to obesity, as well as to plasma SAA concentrations. Objective This study aimed to investigate whether estimated SCD activity mediates the associations between plasma SAAs and measures of overall adiposity and specific fat depots. Methods We examined cross-sectional data from a subset of the Maastricht Study (n=1129, 50.7% men, 56.7% with (pre)diabetes). Concentrations of methionine, total homocysteine, cystathionine, total cysteine (tCys), total glutathione (tGSH) and taurine were measured in fasting plasma. Outcomes included measures of overall, peripheral and central adiposity, and liver fat. SCD activity was estimated by ratios of serum fatty acids as SCD16 and SCD18 indices. The associations between plasma SAAs and measures of adiposity or liver fat were examined with multiple linear regression analysis. Multiple mediation analysis was used to investigate whether the significant associations were mediated by SCD16 and SCD18 indices. Results Plasma tCys was positively associated with all adiposity measures (β ranged from 0.15 to 0.30). SCD16 significantly mediated all associations (proportion mediated ranged from 5.1% to 9.7%). Inconsistent mediation effects were found for SCD18. Despite a significant inverse association of plasma tGSH with all adiposity measures (β ranged from -0.08 to -0.16), no significant mediation effect was found. Conclusions Plasma tCys may promote excessive body fat accumulation via upregulation of SCD activity.

• Gregersen, Ida; Narverud, Ingunn; Christensen, Jacob J.; Hovland, Anders Wilhelm; Øyri, Linn Kristin Lie & Ueland, Thor [Show all 11 contributors for this article] (2024). Plasma legumain in familial hypercholesterolemia: associations with statin use and cardiovascular risk markers. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 84(1), p. 24–29. doi: 10.1080/00365513.2024.2309617. Full text in Research Archive Show summary

  Legumain is known to be regulated in atherosclerotic disease and may have both pro- and anti-atherogenic properties. The study aimed to explore legumain in individuals with familial hypercholesterolemia (FH), a population with increased cardiovascular risk. Plasma legumain was measured in 251 subjects with mostly genetically verified FH, of which 166 were adults (≥18 years) and 85 were children and young adults (<18 years) and compared to 96 normolipidemic healthy controls. Plasma legumain was significantly increased in the total FH population compared to controls (median 4.9 versus 3.3 pg/mL, respectively, p < 0.001), whereof adult subjects with FH using statins had higher levels compared to non-statin users (5.7 versus 3.9 pg/mL, respectively, p < 0.001). Children and young adults with FH (p = 0.67) did not have plasma legumain different from controls at the same age. Further, in FH subjects, legumain showed a positive association with apoB, and markers of inflammation and platelet activation (i.e. fibrinogen, NAP2 and RANTES). In the current study, we show that legumain is increased in adult subjects with FH using statins, whereas there was no difference in legumain among children and young adults with FH compared to controls. Legumain was further associated with cardiovascular risk markers in the FH population. However the role of legumain in regulation of cardiovascular risk in these individuals is still to be determined.

• Myhrstad, Mari Charlotte Wik; Ruud, Emilia; Gaundal, Line; Gjøvaag, Terje; Rud, Ida & Retterstøl, Kjetil [Show all 10 contributors for this article] (2024). Gut microbiota, physical activity and/or metabolic markers in healthy individuals - towards new biomarkers of health. Frontiers in Nutrition. 11, p. 1–8. doi: 10.3389/fnut.2024.1438876. Full text in Research Archive Show summary

  Background: The global prevalence of the metabolic disease Type 2 Diabetes (T2D) is increasing. Risk factors contributing to the development of T2D include overweight and obesity, lack of physical activity (PA), and an unhealthy diet. In addition, the gut microbiota has been shown to affect metabolic regulation. Since T2D is preventable, efforts should be put into the discovery of new biomarkers for early detection of individuals at risk of developing the disease. Objective: The objective of the cross-sectional study was to explore the relationship between gut microbiota and physical activity (PA) and/or metabolic markers such as selected amino acids (AA), markers of glycaemic regulation and lipid metabolism and anthropometric measures. Design: Healthy adults (18 and 65 years) with BMI between 18.5 and 27.5 kg/m2 originally recruited to a randomised controlled trial (RCT) (n = 17: six males, eleven females), were included in this exploratory cross-sectional study. Physical activity data was calculated based on a 3-days registration, and blood metabolome, gut microbiota analyses and anthropometric measures from one visit of the intervention were used in this cross-sectional study. Results: Of the 47 gut bacteria analysed, there were a total of 87 significant correlations with AA, PA, body composition and/or metabolic markers. Several of the gut bacteria correlated with both PA, metabolic or anthropometric markers. Conclusion: In this study, we demonstrate associations between gut bacteria and PA and/or metabolic markers including AA in healthy individuals. The results may guide future studies aiming at identifying new and early biomarkers of metabolic health and diseases.

• Johansen, Anja Katrin; Bogsrud, Martin Prøven; Christensen, Jacob J.; Rundblad, Amanda; Narverud, Ingunn & Ulven, Stine Marie [Show all 9 contributors for this article] (2023). Young women with familial hypercholesterolemia have higher LDL-cholesterol burden than men: Novel data using repeated measurements during 12-years follow-up. Atherosclerosis Plus. ISSN 2667-0909. 51, p. 28–34. doi: 10.1016/j.athplu.2023.01.001. Full text in Research Archive Show summary

  Background and aims The concentration and the duration of exposure to low-density lipoprotein cholesterol (LDL-C) (LDL-C burden) is an important determinant of risk for cardiovascular disease and thresholds has recently been estimated. Individuals with familial hypercholesterolemia (FH) have increased risk of premature cardiovascular disease. The overall aim of the present study was to describe differences in LDL-C level and LDL-C burden in females and males with FH visiting an outpatient lipid clinic from a young age, using multiple LDL-C measurements during a follow-up time of 12 years. First, we aimed to study if the LDL-C concentration and the LDL-C burden is different between females and males at ages 0–10, 10–20, 20–30 and >30 years. Second, we aimed to estimate the subject-specific LDL-C burden at age 19 and 30 years, and the proportion of female and male patients that reach suggested LDL-C thresholds indicating high risk of ASCVD. Methods Data was retrospectively collected from medical records of 438 subjects (207 girls and 231 boys) with FH, referred to the Lipid Clinic, Oslo University Hospital below the age of 19 years. The LDL-C burden was estimated based on repeated LDL-C measurements over time. Results Subjects were followed over a period of mean 12.0 (SD 7.0) years, with median 10 years (7–17; 25–75 percentiles, minimum 2), with median 6 (4–9; 25–75 percentiles, minimum 2) available LDL-C measurements, starting at mean age 11 (SD 3.9) years. There was a difference in both LDL-C and LDL-C burden between sexes at different ages. On average, males had lower LDL-C over time, although this difference was less pronounced with age and males also had lower estimated LDL-C burden over time, and this difference was further exacerbated with age. Conclusion Our study shows that young women with FH have a higher LDL-C burden than their male counterparts, potentially explaining the increased excess CVD risk seen among these. It underscores the importance of careful-follow up and early treatment initiation both prior to and after pregnancies in order to limit statin-free periods.

• Øyri, Linn K. L.; Christensen, Jacob J.; Sebert, Sylvain; Thoresen, Magne; Michelsen, Trond M. & Ulven, Stine M. [Show all 12 contributors for this article] (2023). Maternal prenatal cholesterol levels predict offspring weight trajectories during childhood in the Norwegian Mother, Father and Child Cohort Study. BMC Medicine. 21. doi: 10.1186/s12916-023-02742-9. Full text in Research Archive Show summary

  Background Numerous intrauterine factors may affect the offspring’s growth during childhood. We aimed to explore if maternal and paternal prenatal lipid, apolipoprotein (apo)B and apoA1 levels are associated with offspring weight, length, and body mass index from 6 weeks to eight years of age. This has previously been studied to a limited extent. Methods This parental negative control study is based on the Norwegian Mother, Father and Child Cohort Study and uses data from the Medical Birth Registry of Norway. We included 713 mothers and fathers with or without self-reported hypercholesterolemia and their offspring. Seven parental metabolites were measured by nuclear magnetic resonance spectroscopy, and offspring weight and length were measured at 12 time points. Data were analyzed by linear spline mixed models, and the results are presented as the interaction between parental metabolite levels and offspring spline (age). Results Higher maternal total cholesterol (TC) level was associated with a larger increase in offspring body weight up to 8 years of age (0.03 ≤ Pinteraction ≤ 0.04). Paternal TC level was not associated with change in offspring body weight (0.17 ≤ Pinteraction ≤ 0.25). Higher maternal high-density lipoprotein cholesterol (HDL-C) and apoA1 levels were associated with a lower increase in offspring body weight up to 8 years of age (0.001 ≤ Pinteraction ≤ 0.005). Higher paternal HDL-C and apoA1 levels were associated with a lower increase in offspring body weight up to 5 years of age but a larger increase in offspring body weight from 5 to 8 years of age (0.01 ≤ Pinteraction ≤ 0.03). Parental metabolites were not associated with change in offspring height or body mass index up to 8 years of age (0.07 ≤ Pinteraction ≤ 0.99). Conclusions Maternal compared to paternal TC, HDL-C, and apoA1 levels were more strongly and consistently associated with offspring body weight during childhood, supporting a direct intrauterine effect.

• Røstad-Tollefsen, Helen Kathrine; Kolset, Svein Olav; Retterstøl, Kjetil; Rendal, Heidi Hesselberg & Nordstrøm, Marianne (2023). Weight reduction and dietary improvements in a cluster-randomised controlled trial for adults with intellectual disabilities. Food & Nutrition Research (FNR). ISSN 1654-6628. 67. doi: 10.29219/fnr.v67.9505. Full text in Research Archive Show summary

  Background: People with intellectual disabilities (IDs) have an increased risk of obesity and health concerns related to their nutritional status and dietary intake. Objective: To assess the effectiveness of a multi-component intervention on weight, waist circumference (WC), clinical health parameters and dietary habits in a group of overweight and obese adults with mild-to-moderate ID. Design: A 7-month cluster-randomised trial and a 7-month follow-up of the intervention group after the end of intervention when the group received usual care. The intervention consisted of monthly dietary-group courses tailored to the participants’ cognitive abilities and practical skills, monthly nutritional courses for staff, use of behaviour change techniques and nudging. The control group received usual care during the intervention. Results: There were 32 participants aged 22–61 years: 15 in the intervention group and 17 in the control group. After 7 months, a non-significant weight difference (median difference = −1.25 kg; 95% confidence interval [CI] = −2.00; 0.95 vs. +1.00 kg; CI = −1.15; 3.00, P = 0.08) and a significant WC difference were observed between the intervention and control groups (median difference = −3.75 cm; CI: −7.68; 0.11 vs. 0 cm; CI = −3.99; 1.00, P = 0.03), respectively. The median reduction in WC continued in the intervention group during the 7-month follow-up (median difference = −7.50 cm; CI: −13.57; −3.16, P = 0.002). A significant difference in frequency intake of fruit (P = 0.03) and berries (P = 0.004) was observed between the groups after 7 months, supported by a significant increase in measured serum-carotenoid levels in the intervention group after 7 months (median difference = 0.26 mmol/L; CI: −0.12; 0.52, P = 0.007). Conclusions: A significant difference in WC was observed between the groups, accompanied by changes in blood parameters and dietary habits.

• Schreuder, M.M.; Hamkour, S.; Siegers, K.E.; Holven, Kirsten Bjørklund; Johansen, Anja Katrin & Ree, de van de [Show all 14 contributors for this article] (2023). LDL cholesterol targets rarely achieved in familial hypercholesterolemia patients: A sex and gender-specific analysis. Atherosclerosis. ISSN 0021-9150. 384. doi: 10.1016/j.atherosclerosis.2023.03.022. Full text in Research Archive Show summary

  Background and aims Despite lipid lowering therapy (LLT), reaching LDL-C targets in patients with familial hypercholesterolemia (FH) remains challenging. Our aim was to determine attainment of LDL-C target levels and reasons for not reaching these in female and male FH patients. Methods We performed a cross-sectional study of heterozygous FH patients in five hospitals in the Netherlands and Norway. Clinical characteristics and information about LLT, lipid levels and reasons for not being on LDL-C treatment target were retrospectively collected from electronic medical records. Results We studied 3178 FH patients (53.9% women), median age 48.0 (IQR 34.0–59.9) years. Median LDL-C before treatment and on-treatment was higher in women compared to men (6.2 (IQR 5.1–7.3) and 6.0 (IQR 4.9–7.2) mmol/l (p=0.005) and 3.0 (IQR 2.4–3.8) and 2.8 (IQR 2.3–3.5) mmol/L (p<0.001)), respectively. A minority of women (26.9%) and men (28.9%) reached LDL-C target. In patients with CVD, 17.2% of women and 25.8% of men reached LDL-C target. Women received less often high-intensity statins and ezetimibe. Most common reported reasons for not achieving the LDL-C target were insufficient effect of maximum LLT (women 17.3%, men 24.3%) and side effects (women 15.2%, men 8.6%). Conclusions In routine practice, only a minority of women and men with FH achieved their LDL-C treatment target. Extra efforts have to be made to provide FH patients with reliable information on the safety of statins and their long-term effects on CVD risk reduction. If statin treatment is insufficient, alternative lipid lowering therapies such as ezetimibe or PCSK9-inhibitors should be considered.

• Rodriguez-Borjabad, Celia; Narverud, Ingunn; Christensen, Jacob J.; Ibarretxe, Daiana; Andreychuk, Natalia & Girona, Josefa [Show all 13 contributors for this article] (2023). Association between Nordic and Mediterranean diets with lipoprotein phenotype assessed by ¹HNMR in children with familial hypercholesterolemia. Atherosclerosis. ISSN 0021-9150. 373, p. 38–45. doi: 10.1016/j.atherosclerosis.2023.04.009. Full text in Research Archive Show summary

  Background and aims Both Nordic and Mediterranean diets are considered healthy despite notable regional differences. Although these dietary patterns may lower cardiovascular risk, it is unclear if they improve the lipoprotein phenotype in children with familial hypercholesterolemia (FH). The aim is to determine the impact of Nordic and Mediterranean diets on the advanced lipoprotein profile in children with heterozygous FH (HeFH). Methods This was a cross-sectional study performed in children with FH recruited from the Lipid Clinics at Sant Joan University Hospital in Reus (Spain) and Oslo University Hospital (Norway). Two-hundred fifty-six children (mean age 10 y/o; 48% girls): 85 Spanish and 29 Norwegian FH children, and 142 non-FH healthy controls (119 from Spain and 23 from Norway) were included in the study. A pathogenic FH-associated genetic variant was present in 81% of Spanish children with FH and all Norwegian children with FH. An 1H NMR based advanced lipoprotein test (Nightingale®) providing information on the particle number, size and lipid composition of 14 lipoprotein subclasses was performed and correlated to the dietary components. Results Levels of LDL-C, HDL-C and triglycerides were not significantly different between the Nordic and Mediterranean FH groups. Spanish children with FH had more LDL particles, mainly of the large and medium LDL subclasses, than Norwegian FH children. Spanish FH children also had more HDL particles, mainly medium and small, than Norwegian FH children. The mean LDL size of Spanish FH children was larger, while the HDL size was smaller than that of the Norwegian FH children. The HDL particle number and size were the main determinants of differences between the two groups. In Norwegian children with FH, dietary total fat and MUFAs showed a significant correlation with all apolipoprotein B-containing lipoproteins and LDL size, whereas there was no correlation to SFA. A weaker association pattern was observed in the Spanish children. Conclusions The lipoprotein profiles of Spanish and Norwegian children showed differences when studied by 1H NMR. These differences were in part associated with differences in dietary patterns.

• Tore, Elena C.; Eussen, Simone; Bastani, Nasser Ezzatkhah; Dagnelie, Pieter; Elshorbagy, Amany K & Grootswagers, Pol [Show all 14 contributors for this article] (2023). The Associations of Habitual Intake of Sulfur Amino Acids, Proteins and Diet Quality with Plasma Sulfur Amino Acid Concentrations: The Maastricht Study. Journal of Nutrition. ISSN 0022-3166. 153(7), p. 2027–2040. doi: 10.1016/j.tjnut.2023.05.008. Full text in Research Archive
• Christensen, Jacob J.; Arnesen, Erik Kristoffer; Rundblad, Amanda; Telle-Hansen, Vibeke; Narverud, Ingunn & Blomhoff, Rune [Show all 10 contributors for this article] (2023). Dietary fat quality, plasma atherogenic lipoproteins, and atherosclerotic cardiovascular disease: An overview of the rationale for dietary recommendations for fat intake. Atherosclerosis. ISSN 0021-9150. 389. doi: 10.1016/j.atherosclerosis.2023.117433. Full text in Research Archive Show summary

  The scientific evidence supporting the current dietary recommendations for fat quality keeps accumulating; however, a paradoxical distrust has taken root among many researchers, clinicians, and in parts of the general public. One explanation for this distrust may relate to an incomplete overview of the totality of the evidence for the link between fat quality as a dietary exposure, and health outcomes such as atherosclerotic cardiovascular disease (ASCVD). Therefore, the main aim of the present narrative review was to provide a comprehensive overview of the rationale for dietary recommendations for fat intake, limiting our discussion to ASCVD as outcome. Herein, we provide a core framework – a causal model – that can help us understand the evidence that has accumulated to date, and that can help us understand new evidence that may become available in the future. The causal model for fat quality and ASCVD is comprised of three key research questions (RQs), each of which determine which scientific methods are most appropriate to use, and thereby which lines of evidence that should feed into the causal model. First, we discuss the link between low-density lipoprotein (LDL) particles and ASCVD (RQ1); we draw especially on evidence from genetic studies, randomized controlled trials (RCTs), epidemiology, and mechanistic studies. Second, we explain the link between dietary fat quality and LDL particles (RQ2); we draw especially on metabolic ward studies, controlled trials (randomized and non-randomized), and mechanistic studies. Third, we explain the link between dietary fat quality, LDL particles, and ASCVD (RQ3); we draw especially on RCTs in animals and humans, epidemiology, population-based changes, and experiments of nature. Additionally, the distrust over dietary recommendations for fat quality may partly relate to an unclear understanding of the scientific method, especially as applied in nutrition research, including the process of developing dietary guidelines. We therefore also aimed to clarify this process. We discuss how we assess causality in nutrition research, and how we progress from scientific evidence to providing dietary recommendations.

• Vinknes, Kathrine Jørgensen; Olsen, Thomas; Zare, Hasse Khiabani; Bastani, Nasser Ezzatkhah; Stolt, Emma Theresia Kjelland & Dahl, Anja Falkenhaug [Show all 11 contributors for this article] (2023). Cysteine-lowering treatment with mesna against obesity: Proof of concept and results from a human phase I, dose-finding study. Diabetes, obesity and metabolism. ISSN 1462-8902. 25(11), p. 3161–3170. doi: 10.1111/dom.15210. Full text in Research Archive Show summary

  Abstract Aim To investigate whether mesna—sodium‐2‐mercaptoethane sulfonate) can reduce diet‐induced fat gain in mice, and to assess the safety of single ascending mesna doses in humans to find the dose associated with lowering of plasma tCys by at least 30%. Methods C3H/HeH mice were shifted to a high‐fat diet ± mesna in drinking water; body composition was measured at weeks 0, 2 and 4. In an open, phase I, single ascending dose study, oral mesna (400, 800, 1200, 1600 mg) was administered to 17 men with overweight or obesity. Mesna and tCys concentrations were measured repeatedly for a duration of 48 hours postdosing in plasma, as well as in 24‐hour urine. Results Compared with controls, mesna‐treated mice had lower tCys and lower estimated mean fat mass gain from baseline (week 2: 4.54 ± 0.40 vs. 6.52 ± 0.36 g; week 4: 6.95 ± 0.35 vs. 8.19 ± 0.34 g; P overall  = .002), but similar lean mass gain. In men with overweight, mesna doses of 400‐1600 mg showed dose linearity and were well tolerated. Mesna doses of 800 mg or higher decreased plasma tCys by 30% or more at nadir (4h post‐dosing). With increasing mesna dose, tCys AUC 0‐12h decreased ( P trend  &lt; .001), and urine tCys excretion increased ( P trend  = .004). Conclusions Mesna reduces diet‐induced fat gain in mice. In men with overweight, single oral doses of mesna (800‐1600 mg) were well tolerated and lowered plasma tCys efficiently. The effect of sustained tCys‐lowering by repeated mesna administration on weight loss in humans deserves investigation.

• Melnes, Torunn; Bogsrud, Martin Prøven; Thorsen, Ida; Fossum, Julie; Christensen, Jacob J. & Narverud, Ingunn [Show all 9 contributors for this article] (2022). What characterizes event-free elderly FH patients? A comprehensive lipoprotein profiling. NMCD. Nutrition Metabolism and Cardiovascular Diseases. ISSN 0939-4753. 32(7), p. 1651–1660. doi: 10.1016/j.numecd.2022.03.028. Full text in Research Archive Show summary

  Familial hypercholesterolemia (FH) is a genetic disorder characterized by lifelong elevated low-density lipoprotein cholesterol (LDL-C) and increased risk of pre- mature coronary heart disease (CHD). Cholesterol-lowering therapy (statins) reduces CHD risk, but have been available only in the last 25 years, thus, elderly FH patients have been exposed to elevated LDL-C levels most of their life. Surprisingly, some of these have never experienced any CHD event, raising the question whether they present CHD resistant characteristics. Identifying possible cardioprotective biomarkers could contribute to future CHD preventive treatment, therefore, we aimed to identify metabolic markers in event-free elderly FH subjects. Methods and results: We used a high-throughput nuclear magnetic resonance (NMR) spectroscopy platform to quantify a large number of metabolites in serum samples from 83 FH patients >65 years, and analyze differences between subjects with (n = 39) and without (n = 44) CHD. Mean age was 70 years in both groups (57% and 38% female in the event-free group and CHD group, respectively). The event-free group had significantly higher levels of large and extra-large high-density lipoprotein (HDL) particles, and higher concentration of Apolipoprotein A1 (ApoA1) and cholesterol in HDL and HDL2 particles, compared to the CHD group (p < 0.05 for all). Conclusion: CHD resistant elderly FH patients have higher levels of large HDL particles. The mechanisms behind the event-free survival among these patients remain unclear; hence, a deeper understanding of the metabolic profile in event-free elderly FH subjects may lead to development of novel preventive therapies.

• Christensen, Jacob Juel; Bogsrud, Martin Prøven; Holven, Kirsten Bjørklund; Retterstøl, Kjetil; Veierød, Marit Bragelien & Nordeng, Hedvig Marie Egeland (2022). Use of statins and other lipid-modifying agents across pregnancy: A nationwide drug utilization study in Norway in 2005–2018. Atherosclerosis. ISSN 0021-9150. p. 1–10. doi: 10.1016/j.atherosclerosis.2022.11.022. Full text in Research Archive Show summary

  Background and aims Statins are becoming more widely used among women of reproductive age; however, nationwide data on statin use across pregnancy is scarce. We therefore aimed to describe the drug utilization patterns for statins and other lipid-modifying agents (LMAs) before, during, and after pregnancy, for all pregnancies in Norway from 2005 to 2018. Methods We linked individual-level data from four nationwide electronic health care registries in Norway and characterized the prescription fills of statins and other LMAs across pregnancy. We also examined trends in pregnancy-related LMA use, and characterized women using statins and other LMAs on parameters of health status and co-morbidity. Results In total, 822,071 pregnancies for 503,723 women were included. The number of statin prescription fills decreased rapidly during the first trimester and returned to pre-pregnancy levels about one year postpartum. Pregnancy-related statin use increased from 2005 (approx. 0.11% of all pregnancies) to 2018 (approx. 0.29% of all pregnancies); however, in total, few statin prescriptions were filled within any trimester of pregnancy (n = 331, 0.04% of all pregnancies). Statin use was more common in women with higher age, higher weight, smoking, and comorbidities such as hypertension and diabetes mellitus; also, statin users often had co-medication pertinent to these conditions. Conclusions Although statins and other LMAs were increasingly being used around the time of pregnancy among women in Norway, drug use was mostly discontinued during the first trimester. Our results suggest that pregnancy-related statin use should be monitored, and that drug safety analyses for maternal and offspring health outcomes are needed.

• Christensen, Jacob Juel; Bogsrud, Martin Prøven; Holven, Kirsten Bjørklund; Retterstøl, Kjetil; Veierød, Marit Bragelien & Nordeng, Hedvig Marie Egeland (2022). Use of statins and other lipid-modifying agents across pregnancy – a nationwide drug utilization study of 822 071 pregnancies in Norway in 2005-2018. medRxiv. doi: 10.1101/2022.06.28.22276237. Full text in Research Archive
• Hovland, Anders; Mundal, Liv; Veierød, Marit Bragelien; Holven, Kirsten Bjørklund; Bogsrud, Martin Prøven & Tell, Grethe Seppola [Show all 8 contributors for this article] (2022). The risk of various types of cardiovascular diseases in mutation positive familial hypercholesterolemia; a review. Frontiers in Genetics. 13. doi: 10.3389/fgene.2022.1072108. Full text in Research Archive Show summary

  Familial hypercholesterolemia (FH) is a common, inherited disease characterized by high levels of low-density lipoprotein Cholesterol (LDL-C) from birth. Any diseases associated with increased LDL-C levels including atherosclerotic cardiovascular diseases (ASCVDs) would be expected to be overrepresented among FH patients. There are several clinical scoring systems aiming to diagnose FH, however; most individuals who meet the clinical criteria for a FH diagnosis do not have a mutation causing FH. In this review, we aim to summarize the literature on the risk for the various forms of ASCVD in subjects with a proven FH-mutation (FH+). We searched for studies on FH+ and cardiovascular diseases and also included our and other groups published papers on FH + on a wide range of cardiovascular and other diseases of the heart and vessels. FH + patients are at a markedly increased risk of a broad range of ASCVD. Acute myocardial infarction (AMI) is the most common in absolute numbers, but also aortic valve stenosis is by far associated with the highest excess risk. Per thousand patients, we observed 3.6 incident AMI per year compared to 1.9 incident aortic valve stenosis, however, standardized incidence ratio (SIR) for incident AMI was 2.3 compared to 7.9 for incident aortic valve stenosis. Further, occurrence of ischemic stroke seems not to be associated with increased risk in FH+. Clinicians should be aware of the excess risk of almost all kind of ASCVD in FH+, and the neutral risk of stroke need to be studied further in FH + patients.

• Svilaas, Tone; Klemsdal, Tor Ole; Bogsrud, Martin Prøven; Græsdal, Asgeir; Vesterbekkmo, Elisabeth Kleivhaug & Asprusten, Emil Andreas [Show all 8 contributors for this article] (2022). Høyt nivå av lipoprotein(a) – utredning og behandling. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(1). doi: 10.4045/tidsskr.21.0800. Full text in Research Archive Show summary

  Omtrent 5 % av befolkningen har betydelig forhøyet verdi av lipoprotein(a) (Lp(a)), som er en arvelig betinget risikofaktor for hjerte- og karsykdom. Måling av lipoprotein(a) kan bedre kardiovaskulær risikostratifisering og ha konsekvenser for forebyggende tiltak. Behandlingen er rettet mot en reduksjon av modifiserbare kardiovaskulære risikofaktorer, men Lp(a)-reduserende medikamenter er under utprøving. Denne artikkelen gir en oversikt over håndtering av lipoprotein(a) i klinisk praksis.

• Gaundal, Line; Myhrstad, Mari; Rud, Ida; Gjøvaag, Terje; Byfuglien, Marte G. & Retterstøl, Kjetil [Show all 9 contributors for this article] (2022). Gut microbiota is associated with dietary intake and metabolic markers in healthy individuals. Food & Nutrition Research (FNR). ISSN 1654-6628. 66. doi: 10.29219/fnr.v66.8580. Full text in Research Archive Show summary

  Background: Metabolic diseases have been related to gut microbiota, and new knowledge indicates that diet impacts host metabolism through the gut microbiota. Identifying specific gut bacteria associated with both diet and metabolic risk markers may be a potential strategy for future dietary disease prevention. However, studies investigating the association between the gut microbiota, diet, and metabolic markers in healthy indi-viduals are scarce.Objective: We explored the relationship between a panel of gut bacteria, dietary intake, and metabolic and anthropometric markers in healthy adults.Design: Forty-nine volunteers were included in this cross-sectional study. Measures of glucose, serum tri-glyceride, total cholesterol, hemoglobin A1c (HbA1c), blood pressure (BP), and body mass index (BMI) were collected after an overnight fast, in addition to fecal samples for gut microbiota analyzes using a targeted approach with a panel of 48 bacterial DNA probes and assessment of dietary intake by a Food Frequency Questionnaire (FFQ). Correlations between gut bacteria, dietary intake, and metabolic and anthropometric markers were assessed by Pearson’s correlation. Gut bacteria varying according to dietary intake and metabolic markers were assessed by a linear regression model and adjusted for age, sex, and BMI.Results: Of the 48 gut bacteria measured, 24 and 16 bacteria correlated significantly with dietary intake and metabolic and/or anthropometric markers, respectively. Gut bacteria including Alistipes, Lactobacillus spp., and Bacteroides stercoris differed according to the intake of the food components, fiber, sodium, saturated fatty acids, and dietary indices, and metabolic markers (BP and total cholesterol) after adjustments. Notably, Bacteroides stercoris correlated positively with the intake of fiber, grain products, and vegetables, and higher Bacteroides stercoris abundance was associated with higher adherence to Healthy Nordic Food Index (HNFI) and lower diastolic BP after adjustment.Conclusion: Our findings highlight the relationship between the gut microbiota, diet, and metabolic mark-ers in healthy individuals. Further investigations are needed to address whether these findings are causally linked and whether targeting these gut bacteria can prevent metabolic diseases.

• Tore, Elena C.; Elshorbagy, Amany K.; Bakers, Frans CH; Brouwers, Marin C.G.J.; Dagnelie, Pieter & Eussen, Simone J. [Show all 17 contributors for this article] (2022). Associations between plasma sulfur amino acids and specific fat depots in two independent cohorts: CODAM and The Maastricht Study. European Journal of Nutrition. ISSN 1436-6207. doi: 10.1007/s00394-022-03041-4. Full text in Research Archive Show summary

  Abstract Purpose Sulfur amino acids (SAAs) have been associated with obesity and obesity-related metabolic diseases. We investigated whether plasma SAAs (methionine, total cysteine (tCys), total homocysteine, cystathionine and total glutathione) are related to specific fat depots. Methods We examined cross-sectional subsets from the CODAM cohort ( n  = 470, 61.3% men, median [IQR]: 67 [61, 71] years) and The Maastricht Study (DMS; n  = 371, 53.4% men, 63 [55, 68] years), enriched with (pre)diabetic individuals. SAAs were measured in fasting EDTA plasma with LC–MS/MS. Outcomes comprised BMI, skinfolds, waist circumference (WC), dual-energy X-ray absorptiometry (DXA, DMS), body composition, abdominal subcutaneous and visceral adipose tissues (CODAM: ultrasound, DMS: MRI) and liver fat (estimated, in CODAM, or MRI-derived, in DMS, liver fat percentage and fatty liver disease). Associations were examined with linear or logistic regressions adjusted for relevant confounders with z-standardized primary exposures and outcomes. Results Methionine was associated with all measures of liver fat, e.g ., fatty liver disease [CODAM: OR = 1.49 (95% CI 1.19, 1.88); DMS: OR = 1.51 (1.09, 2.14)], but not with other fat depots. tCys was associated with overall obesity, e.g., BMI [CODAM: β  = 0.19 (0.09, 0.28); DMS: β  = 0.24 (0.14, 0.34)]; peripheral adiposity, e.g., biceps and triceps skinfolds [CODAM: β  = 0.15 (0.08, 0.23); DMS: β  = 0.20 (0.12, 0.29)]; and central adiposity, e.g., WC [CODAM: β  = 0.16 (0.08, 0.25); DMS: β  = 0.17 (0.08, 0.27)]. Associations of tCys with VAT and liver fat were inconsistent. Other SAAs were not associated with body fat. Conclusion Plasma concentrations of methionine and tCys showed distinct associations with different fat depots, with similar strengths in the two cohorts.

• Aaseth, Jan; Rootwelt, Helge; Retterstøl, Kjetil; Hestad, Knut & Farup, Per Grønaas (2022). Circulating Lipoproteins in Subjects with Morbid Obesity Undergoing Bariatric Surgery with Gastric Bypass or Sleeve Gastrectomy. Nutrients. 14(12). doi: 10.3390/nu14122381. Full text in Research Archive Show summary

  The efficacy of various bariatric procedures on the mitigation of the obese dyslipidemia remains debated, and the impact of these measures on lipoprotein(a) (Lp(a)) levels is unknown. In this study we aimed to compare the two most commonly used procedures: gastric bypass (RYGB) and sleeve gastrectomy (SG). Adult patients with morbid obesity were assigned to receive either RYGB or SG. The levels of non-HDL cholesterol, LDL/HDL-ratio and Lp(a) at examinations conducted 6 and 12 months postoperatively were determined and compared to preoperative levels to estimate the efficacy of the two surgical methods. All results 6 and 12 months after surgery were used in the comparisons with the preoperative results. A linear mixed regression model for repeated analyses was used. The Lp(a) and the non-HDL cholesterol levels were considerably reduced in the RYGB group, in contrast to the minor changes in the SG group. In addition, the LDL/HDL ratio was significantly more reduced in the RYGB group when compared to the SG group. Conclusively, RYGB was found to be more efficient than SG for the mitigation of obese dyslipidemia, including preoperative high Lp(a)-levels. This might have important individual and societal implications, especially regarding the potential to reduce the risk of cardiovascular disease and the related societal costs.

• Svendsen, Karianne; Olsen, Thomas; Vinknes, Kathrine Jørgensen; Mundal, Liv; Holven, Kirsten Bjørklund & Bogsrud, Martin Prøven [Show all 9 contributors for this article] (2022). Risk of stroke in genetically verified familial hypercholesterolemia: A prospective matched cohort study. Atherosclerosis. ISSN 0021-9150. 358, p. 34–40. doi: 10.1016/j.atherosclerosis.2022.08.015. Full text in Research Archive Show summary

  Background and aims: Individuals with familial hypercholesterolemia (FH), causing severely elevated LDL-C, are expected to have a higher risk of ischemic stroke. The risk of hemorrhagic stroke and impact of statin use are, however, not known. We aimed to investigate the risk of incident total, ischemic and hemorrhagic stroke in individuals with FH compared to controls, and to explore the association between cumulative statin use and risk of total stroke in FH. Methods: This prospective cohort study consists of 4186 individuals with genetically verified FH and 82 180 age and sex matched controls followed from 2008 to 2018 for incident stroke. Daily defined doses (DDD) described cumulative statin exposure: 0–5000 DDD (“low”), 5000–10,000 DDD (“intermediate”), and >10 000 DDD (“high”). Results were presented as hazard ratio (95% CI) derived from Cox proportional hazards models. Results: Individuals with FH did not have a higher risk of total stroke (1.16 (0.95–1.43) nor ischemic stroke (1.11 (0.88–1.38). Excess risk of hemorrhagic stroke was observed (1.63 (1.07, 2.48) but attenuated after adjusting for antithrombotic medication (1.25 (0.81, 1.93). Among individuals with FH, there was no association between statin use and total stroke for intermediate vs. low DDD [0.69 (0.32, 1.48)] or for high vs. low DDD [0.83 (0.41, 1.67)]. Conclusions: No significant excess risk of incident total and ischemic stroke in FH, and no difference in total stroke risk among the FH population with low, intermediate, and high statin exposure were observed. The observed relationship between FH and hemorrhagic stroke was no longer significant after adjusting for use of anti- thrombotic medication.

• Urke, Eli Bjørnøy; Igland, Jannicke; Mundal, Liv; Holven, Kirsten Bjørklund; Retterstøl, Kjetil & Svendsen, Karianne (2022). Individuals with familial hypercholesterolemia have excess risk of eating disorders: a prospectively matched cohort study. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 30(4). doi: 10.1093/eurjpc/zwac291. Full text in Research Archive
• Telle-Hansen, Vibeke; Gaundal, Line; Bastani, Nasser Ezzatkhah; Rud, Ida; Byfuglien, Marte G. & Gjøvaag, Terje [Show all 10 contributors for this article] (2022). Replacing saturated fatty acids with polyunsaturated fatty acids increases the abundance of Lachnospiraceae and is associated with reduced total cholesterol levels-a randomized controlled trial in healthy individuals. Lipids in Health and Disease. 21, p. 1–13. doi: 10.1186/s12944-022-01702-1. Full text in Research Archive Show summary

  Improving dietary fat quality strongly affects serum cholesterol levels and hence the risk of cardiovascular diseases (CVDs). Recent studies have identified dietary fat as a potential modulator of the gut microbiota, a central regulator of host metabolism including lipid metabolism. We have previously shown a significant reduction in total cholesterol levels after replacing saturated fatty acids (SFAs) with polyunsaturated fatty acids (PUFAs). The aim of the present study was to investigate the effect of dietary fat quality on gut microbiota, short-chain fatty acids (SCFAs), and bile acids in healthy individuals. In addition, to investigate how changes in gut microbiota correlate with blood lipids, bile acids, and fatty acids.

• Arnesen, Erik Kristoffer & Retterstøl, Kjetil (2022). Secular trends in serum lipid profiles in young adults in Norway, 2001-19. Atherosclerosis Plus. ISSN 2667-0909. 48, p. 60–67. doi: 10.1016/j.athplu.2022.03.006. Full text in Research Archive Show summary

  Background Lower prevalence of major cardiovascular disease (CVD) risk factors, such as dyslipidemia, hypertension and smoking, can explain a substantial part of the decline in CVD mortality and incidence for the past decades in Western countries. However, some studies have indicated less favorable trends in risk factors in recent years. We have assessed time trends in lipid profiles among young adults in Norway measured between 2001 and 2019. Methods Samples of serum lipids analyzed at one large medical laboratory in Oslo, Norway, mainly requisitioned by primary care physicians, were analyzed cross-sectionally to estimate year-to-year trends among men and women aged 18–49 years. We also assessed the lipid distributions and proportions with adverse lipid levels. Results In total, more than 2,6 million blood samples, comprising more than 1 million individuals (mean age 37.7 years) from all regions of Norway were included. All measures improved among all age groups in both women and men, especially in total and non-HDL cholesterol (-0.22 and -0.25 mmol/l per decade, respectively). There were downward shifts in the population distribution of total, non-HDL-C and LDL-C. The overall prevalences of total cholesterol ≥5.0 mmol/l and non-HDL-C ≥3.9 mmol/l similarly decreased, from ∼63 to 46% and from ∼52 to 34%, respectively. More than 1/3 had elevated levels of total and/or non-HDL-C in 2019. Conclusion In a large proportion of the Norwegian population aged 18–49 years old, the lipid profiles improved during the last two decades. As the use of lipid-lowering medications is low in this age group, this likely reflects favorable secular trends.

• Mundal, Liv; Igland, Jannicke; Svendsen, Karianne; Holven, Kirsten Bjørklund; Leren, Trond Paul & Retterstøl, Kjetil (2022). Association of familial hypercholesterolemia and statin use with risk of dementia in Norway. JAMA Network Open. 5:e227715(4), p. 1–11. doi: 10.1001/jamanetworkopen.2022.7715. Full text in Research Archive Show summary

  IMPORTANCE Hypercholesterolemia, which is a cardiovascular risk factor, may also be associated with dementia risk. The benefit of statin treatment on dementia risk is controversial. OBJECTIVE To determine whether individuals with familial hypercholesterolemia (FH), who have been exposed to lifelong hypercholesterolemia, have an excess risk of dementia and whether statin use is associated with dementia risk. DESIGN, SETTING, AND PARTICIPANTS This was a prospective cohort study performed from 2008 to 2018 in Norway. Statistical analysis was performed from January 2021 to February 2022. This study included individuals with genetically verified FH and age-matched and sex-matched controls obtained from the general Norwegian population. EXPOSURES Dementia was defined according to International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes F00-03 and G30. MAIN OUTCOMES AND MEASURES Incident cases of total dementia, vascular dementia, Alzheimer disease–dementia in Alzheimer disease, and data on lipid-lowering medication were obtained from the Norwegian Patient Registry, Cause of Death Registry, and the Norwegian Prescription Database. Hazard ratios (HRs) for risk of dementia for individuals with FH vs matched controls were calculated using Cox regression. The cumulative sum of defined daily doses (DDDs) of statins prescribed during study follow-up was calculated for individuals with FH and was analyzed as a time-varying covariate with 3 levels: 1 to 4999 DDDs, 5000 to 10 000 DDDs, and more than 10 000 DDDs. RESULTS Among the 3520 individuals with FH (1863 women [52.9%]; mean [SD] age at the start of follow-up, 51.8 [11.5] years) and the 69 713 controls (36 958 women [53.0%]; mean [SD] age at the start of follow-up, 51.7 [11.5] years), 62 patients with FH (39 women [62.9%]) and 1294 controls (801 women [61.9%]) had developed dementia over the course of 10 years of follow-up. Most dementia cases occurred among individuals aged 70 years and older (39 patients with FH [62.9%] and 870 patients [67.2%] in the control group). We found no excess risk of dementia in patients with FH vs matched controls (HR for total dementia, 0.9; 95% CI, 0.7-1.2). There was no association between cumulative DDDs of statins and total dementia in patients with FH with HRs of 1.2 (95% CI, 0.4-3.8) for cumulative DDDs of 5000 to 10 000 and 1.9 (95% CI, 0.7-5.0) for cumulative DDDs greater than 10 000. CONCLUSIONS AND RELEVANCE These findings suggest that individuals with FH have no excess risk of dementia compared with age-matched and sex-matched controls and that there is no association between use of statins and risk of dementia in patients with FH

• Sørlie, Vilde; Soysa, Ann Kristin Hjelle De; Hyldmo, Åsne Ask; Retterstøl, Kjetil; Martins, Catia & Nymo, Siren (2021). Effect of a ketogenic diet on pain and quality of life in patients with lipedema: The LIPODIET pilot study. Obesity Science & Practice. doi: 10.1002/osp4.580. Full text in Research Archive Show summary

  Background Lipedema is an underdiagnosed condition in women, characterized by a symmetrical increase in subcutaneous adipose tissue (SAT) in the lower extremities, sparing the trunk. The lipedema SAT has been found to be resistant to diet, exercise and bariatric surgery, in regard to both weight loss (WL) and symptom relief. Current experience indicates that a low carbohydrate and high fat (LCHF-diet) might have a beneficial effect on weight and symptom management in lipedema. Objective To assess the impact of an eucaloric low carbohydrate, high fat (LCHF)-diet on pain and quality of life (QoL) in patients with lipedema. Methods Women diagnosed with lipedema, including all types and stages affecting the legs, (age 18-75 years, BMI 30-45 kg/m2) underwent 7 weeks (wk) of LCHF-diet and, thereafter 6 wk of a diet following the Nordic nutrition recommendations. Pain (visual analog scale) and QoL (questionnaire for lymphedema of the limbs), weight and body composition were measured at baseline, wk 7 and 13. Results Nine women (BMI: 36.7±4.5kg/m2 and age: 46.9±7 years) were recruited. The LCHF diet induced a significant WL -4.6±0.7 kg (-4.5±2.4%), P<0.001 for both, and reduction in pain (-2.3±0.4 cm, P=0.020). No correlation was found between WL and changes in pain at wk 7 (r = 0.283, P = 0.460). WL was maintained between wk 7 and 13 (0.3±0.7 kg, P=0.430), but pain returned to baseline levels at wk 13 (4.2±0.7 cm ,P=0.690). A significant increase in general QoL was found between baseline and wk 7 (1.0 (95% CI (2.0, 0.001), P=0.050) and 13 (1.0 95% CI (2.0, 0.001) P=0.050), respectively. Conclusion A LCHF-diet is associated with reduction in perceived pain and improvement in QoL, in patients with lipedema. Larger randomized clinical trials are needed to confirm these findings.

• Øyri, Linn Kristin Lie; Bogsrud, Martin Prøven; Kristiansen, Anne Lene; Myhre, Jannicke Borch; Astrup, Helene & Retterstøl, Kjetil [Show all 10 contributors for this article] (2021). Cholesterol at ages 6, 12 and 24 months: Tracking and associations with diet and maternal cholesterol in the Infant Cholesterol Study. Atherosclerosis. ISSN 0021-9150. 326, p. 11–16. doi: 10.1016/j.atherosclerosis.2021.04.017. Full text in Research Archive Show summary

  Background and aims: There are indications for tracking of circulating total cholesterol concentration (TC) from childhood to later in life. An increased lifelong TC exposure increases the risk of developing atherosclerosis, however little is known about the determinants of TC early in life. We aimed to describe TC in Norwegian offspring aged 6, 12 and 24 months, and to explore if maternal TC, breastfeeding and offspring diet are associated with offspring TC. Methods: In this cross-sectional study, mothers of offspring aged 6 (n = 629), 12 (n = 258) and 24 (n = 263) months completed a questionnaire of the offspring's diet and took home-based dried blood spot samples from themselves and their offspring. The mothers and offspring participating at age 12 months also participated at age 6 months of the offspring. Results: Offspring TC showed a wide range in all three age groups. Twenty one percent of the offspring had TC ≥ 5.1 mmol/l. There was significant tracking of offspring TC from 6 to 12 months of age (r = 0.42, p < 0.001). Maternal and offspring TC was positively associated in all age groups (0.20 ≤ β ≤ 0.40, p < 0.001 for all). Breastfeeding was positively associated with offspring TC at ages 6 and 12 months (0.05 ≤ β ≤ 0.26, 0.001 ≤ p ≤ 0.03), but not at age 24 months. Conclusions: The wide range in TC and probable tracking of TC from infancy to later in life highlights the importance of early identification of children with elevated TC who can benefit from preventive measures.

• Berglund, Ida Johnsen; Vesterbekkmo, Elisabeth Kleivhaug; Retterstøl, Kjetil; Anderssen, Sigmund Alfred; Singh, Maria A. Fiatarone & Helge, Jørn Wulff [Show all 9 contributors for this article] (2021). The Long-term Effect of Different Exercise Intensities on High-Density Lipoprotein Cholesterol in Older Men and Women Using the Per Protocol Approach: The Generation 100 Study. Mayo Clinic Proceedings: Innovations, Quality & Outcomes (MCP:IQ&O). 5(5), p. 859–871. doi: 10.1016/j.mayocpiqo.2021.07.002. Full text in Research Archive Show summary

  Objective: To examine whether 5 years of high-intensity interval training (HIIT) increases high-density lipoprotein cholesterol (HDL-C) concentration more than moderate-intensity continuous training (MICT) and control (CON) in older men and women. Methods: A total of 1567 older adults (790 [50.4%] women) were randomized (2:1:1) to either CON (n=780; asked to follow the national recommendations for physical activity) or 2 weekly sessions of HIIT (10-minute warm-up followed by 4×4-minute intervals at ∼90% of peak heart rate) or MICT (50 minutes of continuous work at ∼70% of peak heart rate). Serum HDL-C concentration was measured by standard procedures at baseline and at 1 year, 3 years, and 5 years. The study took place between August 21, 2012, and June 31, 2018. Linear mixed models were used to determine between-group differences during 5 years using the per protocol approach. Results: Men in HIIT had a smaller reduction in HDL-C (−1.2%) than men in CON (−6.9%) and MICT (−7.8%) after 5 years (P=.01 and P=.03 for CON vs HIIT and MICT vs HIIT, respectively). No effect of exercise intensity on HDL-C was seen in women. Changes in peak oxygen uptake were associated with changes in HDL-C in both men and women, whereas changes in body weight and fat mass were not. Conclusion: In men, HIIT seems to be the best strategy to prevent a decline in HDL-C during a 5-year period. No effect of exercise intensity was seen for older women.

• Johansen, Anja Katrin; Bogsrud, Martin Prøven; Lennep, Jeanine Roeters van; Narverud, Ingunn; Langslet, Gisle & Retterstøl, Kjetil [Show all 7 contributors for this article] (2021). Long term follow-up of children with familial hypercholesterolemia and relatively normal LDL-cholesterol at diagnosis. Journal of Clinical Lipidology. ISSN 1933-2874. p. 1–4. doi: 10.1016/j.jacl.2021.01.007. Full text in Research Archive
• Arnesen, Kjell Erik; Phung, Ann Vinh; Randsborg, Karoline; Mork, Irene; Thorvall, Marlene & Langslet, Gisle [Show all 10 contributors for this article] (2021). Risk of recurrent coronary events in patients with familial hypercholesterolemia; A 10-years prospective study. Frontiers in Pharmacology. 11, p. 1–8. doi: 10.3389/fphar.2020.560958. Full text in Research Archive Show summary

  Background and Aim: Real world evidence on long term treatment of patients with familial hypercholesterolemia (FH) is important. We studied the effects of intensive lipid lowering medication (LLM) and optimized lifestyle in the study TTTFH–Treat To Target FH. Materials and Methods: Adults with a first known total cholesterol of mean (95% CI) 9.8 mmol/L (9.5, 10.1) were included consecutively in their routine consultation during 2006. Of the patients 86.4% had a pathogenic FH-mutation and the remaining were clinically diagnosed. We included 357 patients and 279 met for follow-up after median 10.0 (min 8.1, max 12.8) years. Results: Mean (95% CI) low density lipoprotein (LDL-C) was reduced from 3.9 (3.8, 4.1) to 3.0 (2.9, 3.2). More men than women used high intensity statin treatment, 85.2 and 60.8%, respectively. Women ( n = 129) had higher LDL-C; 3.3 mmol/L (3.0, 3.5), than men; ( n = 144) 2.8 mmol/L (2.6, 3.0), p = 0.004. Add-on PCSK9 inhibitors ( n = 25) reduced mean LDL-C to 2.0 (1.4, 2.6) mmol/L. At enrollment 57 patients (20.4%) had established atherosclerotic cardiovascular disease (ASCVD), and 46 (80.4%) of them experienced a new event during the study period. Similarly, 222 (79.6%) patients had no detectable ASCVD at enrollment, and 29 of them (13.1%) experienced a first-time event during the study period. Conclusion: A mean LDL-C of 3.0 mmol/L was achievable in FH, treated intensively at a specialized clinic with few users of PCSK9 inhibitors. LDL-C was higher (0.5 mmol/L) in women than in men. In patients with ASCVD at enrollment, most (80.7%) experienced a new ASCVD event in the study period. The FH patients in primary prevention had more moderate CV risk, 13% in ten years.

• Rodriguez-Borjabad, Celia; Narverud, Ingunn; Christensen, Jacob J.; Ulven, Stine Marie; Malo, Ana Irene & Ibarretxe, Daiana [Show all 13 contributors for this article] (2021). Dietary intake and lipid levels in Norwegian and Spanish children with familial hypercholesterolemia. NMCD. Nutrition Metabolism and Cardiovascular Diseases. ISSN 0939-4753. 31(4), p. 1299–1307. doi: 10.1016/j.numecd.2020.12.002. Full text in Research Archive
• Langslet, Gisle; Johansen, Anja Katrin; Bogsrud, Martin Prøven; Narverud, Ingunn; Risstad, Hilde & Retterstøl, Kjetil [Show all 7 contributors for this article] (2021). Thirty percent of children and young adults with familial hypercholesterolemia treated with statins have adherence issues. American Journal of Preventive Cardiology. 6. doi: 10.1016/j.ajpc.2021.100180. Full text in Research Archive

View all works in NVA

• Hjartåker, Anette; Retterstøl, Kjetil; Müller, Hanne & Anderssen, Sigmund Alfred (2026). Grunnleggende ernæringslære. Gyldendal. ISBN 9788205614734. 485 p. Full text in Research Archive Show summary

  Boken legger særlig vekt på betydningen av samspillet mellom kosthold og fysisk aktivitet for god helse. Innholdet i denne fjerde utgaven er oppdatert i tråd med aktuell forskningslitteratur og nasjonale anbefalinger, og den er spesielt tilpasset norske forhold. Boken henvender seg til et bredt spekter av studenter ved universitets- og høyskoler, blant annet innenfor medisin, ernæring, idrettsfag og fysioterapi, i tillegg til andre fagområder som jobber med forebygging og folkehelse. Boken gir også et solid grunnlag for videre studier innenfor mer spesialiserte, tilgrensende områder som klinisk ernæring, samfunnsernæring og næringsmiddelteknologi.

View all works in NVA

• Khalil, Youssef Samir Abouzeid Mohamed; Vesterbekkmo, Elisabeth Kleivhaug; Holven, Kirsten Bjørklund; Dalen, Håvard; Retterstøl, Kjetil & Blom, Sigrid Marie [Show all 8 contributors for this article] (2026). Excess atherosclerotic cardiovascular burden associated with elevated lipoprotein(a) across age, sex, and cardiometabolic risk factors: insights from 16-year follow-up of the HUNT Study. European Heart Journal. ISSN 0195-668X. 47(Supplement_1). doi: 10.1093/eurheartj/ehag785.3363. Full text in Research Archive Show summary

  Abstract Background Lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD), but prevention strategies should be guided by where the absolute excess burden of events is greatest. Purpose To test additive interaction between elevated Lp(a) and other ASCVD risk factors, and to estimate absolute excess ASCVD hazard associated with elevated Lp(a) across cardiometabolic profiles at different ages. Methods We included 19 495 adults without ASCVD at baseline from the Trøndelag Health Study (2006–08) and followed them for up to 16 years for first ASCVD event. Lp(a) was dichotomised as &gt;105 versus ≤105 nmol/L, and pre-specified risk factors were classified into higher and lower-risk strata. Multivariable cause-specific Cox models were used to estimate hazard ratios (HRs) and to evaluate additive interaction using the relative excess risk due to interaction (RERI). Sex-specific marginal hazards and hazard rate differences (HRDs) of ASCVD per 1000 person-years were estimated at age 60 across cardiometabolic markers. Sensitivity analyses used Lp(a) ≥96th versus 1–74th percentiles. Results HRs were generally highest when elevated Lp(a) coexisted with the higher-risk stratum of the risk factor. Additive interaction was observed for older age (RERI 0.60; 95% CI: 0.10–1.10) and male sex (RERI 0.63; 95% CI: 0.27–0.99). Using ≥96th versus 1–74th percentiles, smoking also showed additive interaction (RERI 0.57; 95% CI: 0.05–1.08). RERI estimates for remaining risk factors were small. At age 60, hazard rates of ASCVD were higher for elevated versus low Lp(a) across all risk factors and were generally larger in men. Across mean systolic blood pressure, the excess burden associated with elevated Lp(a) increased with higher levels in men, reaching 7.88 additional events per 1000 person-years at 180 mmHg (95% CI: -1.38–17.14), whereas women showed a smaller increase (HRD 3.89; 95% CI: -0.74–8.53). Across triglycerides-to-high-density lipoprotein cholesterol (TG:HDL-C) ratio, the excess burden in men peaked around a TG:HDL-C ratio of ~1.4, reaching 7.41 additional events per 1000 person-years (95% CI: 4.42–10.41), while in women the HRDs were relatively constant. In contrast, HRDs varied little across other risk factors, including C-reactive protein, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol. Similar patterns were observed at older ages. Conclusions Elevated Lp(a) shows clinically relevant additive interaction with age and sex, while interaction with most other cardiometabolic risk factors appears limited. Nevertheless, absolute excess ASCVD burden varies across selected cardiometabolic profiles and is consistently greater in men. These findings support a clear communication of the absolute excess burden associated with elevated Lp(a) and may help inform the most relevant target groups for future Lp(a)-lowering therapies. Larger cohorts are needed to confirm these findings.

• Khalil, Youssef Samir Abouzeid Mohamed; Vesterbekkmo, Elisabeth Kleivhaug; Holven, Kirsten Bjørklund; Dalen, Håvard; Retterstøl, Kjetil & Blom, Sigrid Marie [Show all 8 contributors for this article] (2026). LIPOPROTEIN(A), AGE AND SEX-SPECIFIC ABSOLUTE AND RELATIVE HAZARDS OF ATHEROSCLEROTIC CARDIOVASCULAR DISEASE: NEW INSIGHTS FROM 16-YEAR FOLLOW-UP OF THE NORWEGIAN HUNT STUDY. Atherosclerosis. ISSN 0021-9150. 419, p. 121083–121083. doi: 10.1016/j.atherosclerosis.2026.121083. Full text in Research Archive Show summary

  Background and Aims: Atherosclerotic cardiovascular disease (ASCVD) develops through cumulative exposure to causal risk factors, such as lipoprotein(a) [Lp(a)]. Evidence on how high Lp(a) shapes long-term absolute and relative ASCVD hazards across age and sex remains limited. We quantified age and sex-specific absolute and relative ASCVD hazards associated with high Lp(a) and assessed whether these age-related patterns differed between men and women. Methods: We included 19 495 adults without ASCVD at baseline with Lp(a) measured from the Trøndelag Health Study (HUNT3, 2006–08). Participants were followed for up to 16 years for first ASCVD event. Lp(a) was categorized as high (≥95th percentile; ≥252 nmol/L) versus low (≤74th percentile; ≤62 nmol/L). Standardized age and sex-specific hazard rates, hazard ratios (HRs), and hazard rate differences (HRDs) per 1000 person-years were estimated using multivariable cause-specific flexible parametric survival models. Results: High Lp(a) was associated with higher ASCVD hazards at all ages. In both sexes combined, the HR for high versus low Lp(a) declined from 2.42 (95% CI: 1.14–5.14) at age 40 to 1.24 (95% CI: 0.91–1.70) at age 90, while corresponding HRDs increased from 1.22 (95% CI: -0.24–2.67) to 6.97 (95% CI: -4.08–18.02) extra ASCVD events per 1000 person-years. Men had higher ASCVD hazards than women at all ages. HRs were broadly similar between sexes but tended to be slightly higher in women at midlife. However, the number of extra ASCVD events per 1000 person-years due to high Lp(a) increased with age in both sexes and was consistently higher in men compared to women. Conclusions: High Lp(a) is a long-term risk factor for ASCVD across adulthood, with a larger relative impact at younger ages, but causes more excess events in older adults, and particularly in men. These risk profiles may help clinicians prioritize Lp(a) testing and identify patients who may benefit from future Lp(a)-lowering therapies.

• Angelsen, Madeleine Elisabeth; Najar, Hemen; Svendsen, Mette; Thoresen, Magne; Peleikis, Dawn Elisabeth & Retterstøl, Kjetil (2026). Clinical dietitian-led nutrition counseling and exercise to reduce cardiovascular risk in adults living with a BMI above 27 and severe mental illness: the NORMI-Heart trial protocol. doi: 10.3389/fnut.2026.1700251. Full text in Research Archive
• Klevmoen, Marianne; Mulder, Janneke W.C.M.; Bogsrud, Martin Prøven; Retterstøl, Kjetil; Vesterbekkmo, Elisabeth Kleivhaug & Pedersen, Eva Ringdal [Show all 16 contributors for this article] (2025). Prospective study on breastfeeding, lipid profile and cardiovascular risk markers in women with familial hypercholesterolaemia: study protocol for the FH-FEMINA study. doi: 10.1136/bmjopen-2024-092208. Full text in Research Archive
• Mulder, Janneke W. C. M.; Pang, Jing; Klevmoen, Marianne; Kranenburg, Leonieke W.; Retterstøl, Kjetil & Boersma, Eric [Show all 9 contributors for this article] (2025). Family planning, pregnancy, and breastfeeding care in familial hypercholesterolaemia: A study protocol for a mixed-methods study in the Netherlands, Norway and Australia (Taking ACTion to Improve Care of coupleS in FH (TACTICS)). doi: 10.1136/bmjopen-2024-089187. Full text in Research Archive
• Uduma, Amara Synøve; Sverre, Elise Christine Bjørkholen; Munkhaugen, John; Retterstøl, Kjetil; Bogsrud, Martin Prøven & Holven, Kirsten Bjørklund [Show all 7 contributors for this article] (2025). More musculoskeletal disorders and poor pain management in patients with familial hypercholesterolemia and self-perceived side effects to cholesterol-lowering treatment. Full text in Research Archive Show summary

  Purpose: To compare clinical and psychosocial characteristics of patients with FH, with and without self-perceived side effects to cholesterol-lowering treatment. Methods: A group of 929 adult outpatients with confirmed genetic FH from a regional treatment register in Norway were invited to an observational study. The participants completed a digital questionnaire covering self-perceived side effects (any symptoms), use of cholesterol-lowering medications, musculoskeletal disorders or rheumatic diseases, and muscular symptoms and pain treatment. We collected data on FH diagnosis, comorbidities, and biomarkers in blood from the last consultation listed in the treatment register. Results: Mean age was 52 (SD 15) years, and 57% were women. Thirty-eight (15%) out of 255 participants reported self-perceived side effects to cholesterol-lowering treatment. Patients with self-perceived side effects were more frequently living alone (26% vs. 12%, p=0.025) and had slightly higher LDL-C than those without side effects, whereas no differences in creatine kinase or alanine transaminase were observed. Patients with self-perceived side effects had a higher frequency of musculoskeletal disorders or rheumatic diseases (58% vs. 37%, p<0.001) than those with no side effects (Table 1). They also reported more muscle symptoms the last month in general, and specifically from the hips, thighs, calves, shoulders, and neck. Median pain intensity the last 24-hours was significantly higher (3 vs. 1 on a 0 [no] to 10 [worst imaginable] numeric rating scale, p<0.001) in patients with side effects, and 58% currently used no pain medication (Table 2). Conclusions: Patients with FH and self-perceived side effects frequently have musculoskeletal disorders or rheumatic diseases and clinically significant pain without treatment. Our study suggests that a considerable proportion of patients misattribute muscle symptoms and pain to their cholesterol-lowering medications. Future work should focus on musculoskeletal- and rheumatic conditions as an alternative explanation for self-perceived side effects to cholesterol-lowering medication.

• Telle-Hansen, Vibeke; Rundblad, Amanda; Rud, Emilia; Gaundal, Line; Rud, Ida & Retterstøl, Kjetil [Show all 9 contributors for this article] (2025). Metabolic profiling and gene transcription analyses in healthy individuals after exchanging SFA with PUFA: secondary analyses of a randomized controlled trial. Full text in Research Archive Show summary

  Background and objectives: The underlying molecular mechanisms by which diet influences metabolic health are still to be elucidated. In secondary analyses of an RCT, we aimed to investigate the effect on cardiometabolic risk markers in healthy individuals after a short-term intervention with PUFA compared to SFA by using metabolomics and transcriptomics. Materials and methods: Seventeen healthy, normal-weight participants completed a double-blind, crossover RCT. Participants were allocated to receive interventions with PUFA and SFA products in a random order for three consecutive days, separated by a 10-day washout period. We analyzed the effect of the intervention on 155 metabolites mainly related to lipoproteins using nuclear magnetic resonance (NMR) spectroscopy, and the expression of 748 genes related to metabolic pathways using NanoString. Results: The particle concentration of the smallest very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL) and all low-density lipoprotein (LDL) subclasses were reduced after intake of PUFA for three days compared to SFA. We found the same pattern for the particle content of cholesterol, but not triglyceride, in these lipoprotein subclasses. Moreover, the concentration of other atherogenic lipoprotein measures were reduced after intake of PUFA compared to SFA. The expression of 45 genes were significantly altered by PUFA compared to SFA. Several of these genes were related to lipid metabolism and energy homeostasis (such as ALOX15, SLC3A2, ECHS1, STK11, SREBF2, FABP5, and ACACA). Conclusions: This study demonstrated that a three-day intervention with PUFA significantly reduced several atherogenic lipoprotein subclass measures, and the expression of genes related to lipid metabolism in young healthy individuals. This highlights that the dietary fat quality is important to improve the cardiovascular disease risk profile, even in a young healthy population.

• Strømland, Stine Sofie; Aspholm, Trude; Fjørtoft, Jenny; Brønner, Charlotte Utheim; Stolt, Emma & Snipen, Lars-Gustav [Show all 12 contributors for this article] (2024). Effects of sulfur amino acid restriction on gut microbiota and inflammation in people with overweight and obesity: an 8-week randomized controlled dietary intervention study. Full text in Research Archive
• Melnes, Torunn; Bogsrud, Martin Prøven; Christensen, Jacob J.; Rundblad, Amanda; Narverud, Ingunn & Retterstøl, Kjetil [Show all 10 contributors for this article] (2023). Difference in PBMC gene expression between elderly event-free FH patients and FH patients with CHD. Full text in Research Archive
• Melnes, Torunn; Bogsrud, Martin Prøven; Christensen, Jacob J.; Rundblad, Amanda; Narverud, Ingunn & Retterstøl, Kjetil [Show all 10 contributors for this article] (2023). Difference in PBMC gene expression between elderly event-free FH patients and FH patients with CHD. Full text in Research Archive
• Svilaas, Tone & Retterstøl, Kjetil (2023). LDL-kolesterolsenkende behandling i dag og i fremtide. Indremedisineren. ISSN 1891-1617. 4(4), p. 18–20. Full text in Research Archive
• Melnes, Torunn; Bogsrud, Martin Prøven; Thorsen, Ida; Fossum, Julie; Christensen, Jacob J. & Narverud, Ingunn [Show all 9 contributors for this article] (2023). What characterizes event-free elderly FH patients? A comprehensive lipoprotein profiling. Full text in Research Archive
• Retterstøl, Kjetil & Langslet, Gisle (2023). Høye triglyserider-patofysiologi og risiko. Indremedisineren. ISSN 1891-1617. p. 24–26. Full text in Research Archive
• Svilaas, Tone & Retterstøl, Kjetil (2023). Tema - Lipider. Indremedisineren. ISSN 1891-1617. p. 17–17. Full text in Research Archive
• Rundblad, Amanda; Hansen, Anna Lena; Christensen, Jacob Juel; Melnes, Torunn; Ottestad, Inger Olaug & Narverud, Ingunn [Show all 12 contributors for this article] (2023). Patients with familial hypercholesterolemia have shorter telomeres than controls in older, but not in young subjects: a cross-sectional study. Full text in Research Archive
• Semb, Anne Grete; Vesterbekk, Elisabeth Kleivhaug; Retterstøl, Kjetil; Atar, Dan; Solberg, Erik E. & Schirmer, Henrik [Show all 11 contributors for this article] (2023). PCSK9-hemmere på blå resept for hvem? Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(8). doi: 10.4045/tidsskr.23.0191. Full text in Research Archive
• Melnes, Torunn; Bogsrud, Martin Prøven; Christensen, Jacob J.; Rundblad, Amanda; Narverud, Ingunn & Retterstøl, Kjetil [Show all 10 contributors for this article] (2023). Difference in PBMC gene expression between elderly event-free FH patients and FH patients with CHD. Full text in Research Archive
• Vinnes, Erik Wilhelm; Retterstøl, Kjetil & Renstrøm, Renate (2023). Lipoprotein(a) – en kort oversikt over målemetoder, indikasjoner og kliniske beslutningsgrenser. Klinisk Biokemi i Norden. ISSN 1101-2013. 30(4), p. 30–34. Full text in Research Archive
• Troensegaard, Hannibal; Khoury, Janette; Westerberg, Ane Cecilie; Tonstad, Serena; Lennep, Jeanine Roeters van & Veierød, Marit Bragelien [Show all 9 contributors for this article] (2023). Protocol for a 20-year follow-up after a randomized controlled trial of a Mediterranean diet in pregnancy: maternal and offspring risk factors for cardiovascular disease. Frontiers in Pediatrics. 11. doi: 10.3389/fped.2023.1256815. Full text in Research Archive Show summary

  Background: An inadequate maternal diet during pregnancy can impair offspring health and may increase the risk of cardiovascular disease later in life. The purpose of the proposed study is to assess the risk factors associated with cardiovascular disease in both mothers and their offspring 20 years following their participation in a Mediterranean diet intervention trial during pregnancy. Methods: The “Cardiovascular Risk Reduction Diet In Pregnancy” (CARRDIP) study was a randomized controlled trial performed between 1999 and 2001. The participants were randomized to adhere to either a Mediterranean diet or their regular diet during pregnancy. An extensive amount of data such as diet information, ultrasound measurements, anthropometry, and biomarkers from these mothers during pregnancy and their offspring in the neonatal period were collected. The mother–offspring pairs (n = 269) from the CARRDIP study will be invited to participate in a clinical examination and blood sample collection. This follow-up study, conducted 20 years after the original CARRDIP study, will investigate cardiovascular risk factors in mothers and offspring. The primary outcome will be the blood pressure of the offspring. In addition, the study will explore various aspects of cardiovascular health, including metabolic and inflammatory status, clinical history, and body composition of the participants. Discussion: Previous studies investigating the effects of nutrition during pregnancy on maternal and offspring health have been either observational studies, animal studies, or randomized controlled trials with a follow-up period of less than 5 years. This project aims to study the long-term effects of dietary intervention during pregnancy on maternal and offspring cardiovascular risk markers.

• Mundal, Liv; Igland, Jannicke; Svendsen, Karianne; Holven, Kirsten Bjørklund; Leren, Trond Paul & Retterstøl, Kjetil (2022). No excess risk of dementia in individuals with familial hypercholesterolemia compared with age and sex matched controls. Full text in Research Archive
• Svendsen, Karianne; Mundal, Liv; Holven, Kirsten Bjørklund; Igland, Jannicke; Bogsrud, Martin Prøven & Leren, Trond Paul [Show all 7 contributors for this article] (2022). Diseases occuring frequently in a “genetic high LDL-cholesterol (LDL-C) model disease” may be caused by LDL-C itself, or by the treatment of a high LDL-C. Full text in Research Archive
• Svendsen, Karianne; Urke, Eli Bjørnøy; Igland, Jannicke; Mundal, Liv; Holven, Kirsten Bjørklund & Retterstøl, Kjetil (2022). Can disease-related diet treatment from childhood result in eating disorders in adulthood? Full text in Research Archive
• Aaseth, Jan; Rootwelt, Helge; Retterstøl, Kjetil; Hestad, Knut & Farup, Per Grønaas (2022). Reply to Paredes et al. Comment on “Aaseth et al. Circulating Lipoproteins in Subjects with Morbid Obesity Undergoing Bariatric Surgery with Gastric Bypass or Sleeve Gastrectomy. Nutrients 2022, 14, 2381”. Nutrients. 15(1). doi: 10.3390/nu15010053. Full text in Research Archive
• Munkhaugen, John; Kristiansen, Oscar; Sverre, Elise Christine Bjørkholen; Retterstøl, Kjetil & Tonstad, Serena (2022). Statiner gir sjelden bivirkninger. 2. doi: 10.4045/tidsskr.21.0885. Full text in Research Archive
• Svendsen, Karianne; Vinknes, Kathrine Jørgensen; Retterstøl, Kjetil & Olsen, Thomas (2022). Why we can probably trust public policy dietary guidelines for prevention. 29(6), p. e209–e210. doi: 10.1093/eurjpc/zwaa008. Full text in Research Archive
• Klevmoen, Marianne; Bogsrud, Martin Prøven; Retterstøl, Kjetil; Svilaas, Tone; Vesterbekkmo, Elisabeth Kleivhaug & Hovland, Anders Wilhelm [Show all 9 contributors for this article] (2022). Loss of statin treatment years during pregnancy and breastfeeding periods in women with familial hypercholesterolemia. Full text in Research Archive
• Svendsen, Karianne; Olsen, Thomas; Vinknes, Kathrine Jørgensen; Mundal, Liv; Holven, Kirsten Bjørklund & Bogsrud, Martin Prøven [Show all 9 contributors for this article] (2022). No increased risk of stroke in genetically verified familial hypercholesterolemia: a prospective matched cohort study. Full text in Research Archive
• Aaseth, Jan Olav; Rootwelt, Helge; Retterstøl, Kjetil; Hestad, Knut & Farup, Per Grønaas (2022). Reply to Paredes et al. Comment on "Aaseth et al. Circulating Lipoproteins in Subjects with Morbid Obesity Undergoing Bariatric Surgery with Gastric Bypass or Sleeve Gastrectomy. Nutrients 2022, 14, 2381". Nutrients. 15(1). doi: 10.3390/nu15010053. Full text in Research Archive Show summary

  Hereby, we thank Silvia Paredes et al. [...].

• Melnes, Torunn; Bogsrud, Martin Prøven; Thorsen, Ida; Fossum, Julie; Christensen, Jacob J. & Narverud, Ingunn [Show all 9 contributors for this article] (2022). What characterizes event-free elderly FH patients? A comprehensive lipoprotein profiling. Full text in Research Archive
• Munkhaugen, John; Kristiansen, Oskar; Sverre, Elise Christine Bjørkholen; Retterstøl, Kjetil & Tonstad, Serena (2022). Statiner gir sjelden bivirkninger. 142(2). doi: 10.4045/tidsskr.21.0885. Full text in Research Archive
• Urke, Eli Bjørnøy; Igland, Jannicke; Mundal, Liv; Holven, Kirsten Bjørklund; Retterstøl, Kjetil & Svendsen, Karianne (2022). REGISTRY DATA INDICATE HIGHER RISK OF EATING DISORDERS IN INDIVIDUALS WITH FAMILIAL HYPERCHOLESTEROLEMIA COMPARED WITH AGE AND SEX MATCHED CONTROLS. Full text in Research Archive
• Svendsen, Karianne; Mundal, Liv; Holven, Kirsten Bjørklund; Bogsrud, Martin Prøven; Igland, Jannicke & Leren, Trond Paul [Show all 7 contributors for this article] (2022). UNCHANGED HAZARD RATIOS OF INCIDENT ACUTE MYOCARDIAL INFARCTION IN PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA DURING 2001-2017. Full text in Research Archive
• Bastani, Nasser Ezzatkhah; Refsum, Helga; Olsen, Thomas; Vinknes, Kathrine Jørgensen; Retterstøl, Kjetil & Zare, Hasse Khiabani (2022). Determination of plasma thiols using LC-MS/MS: Cysteine-lowering treatment with mesna against obesity: Preliminary results from a phase I dose-finding stud. Full text in Research Archive
• Hope, Sigrun; Terje, Nærland,; Nordstrøm, Marianne; Kolset, Svein Olav; Retterstøl, Kjetil & Aanonsen, Nils Olav [Show all 7 contributors for this article] (2021). Store utfordringer med kosthold ved autisme. Forskning.no. ISSN 1891-635X. Full text in Research Archive
• Melnes, Torunn; Bogsrud, Martin Prøven; Thorsen, Ida; Fossum, Julie; Christensen, Jacob J. & Narverud, Ingunn [Show all 9 contributors for this article] (2021). Event-free FH patients ≥65 years of age are characterized by higher concentration of large HDL particles. Full text in Research Archive
• Retterstøl, Kjetil; Munkhaugen, John; Ingul, Charlotte Björk; Grimsmo, Jostein; Kask, Anne & Schirmer, Henrik [Show all 8 contributors for this article] (2021). Lavere behandlingsmål for LDLkolesterol bør innføres. 141(2), p. 1–6. doi: 10.4045/tidsskr.20.0761. Full text in Research Archive
• Christensen, Jacob Juel; Narverud, Ingunn; Ruuth, Maija; Heier, Martin; Jauhiainen, Matti & Ulven, Stine Marie [Show all 14 contributors for this article] (2021). Children with FH display changes in LDL and HDL function: a cross-sectional study. Full text in Research Archive
• Christensen, Jacob Juel; Bogsrud, Martin Prøven; Holven, Kirsten Bjørklund; Retterstøl, Kjetil; Veierød, Marit Bragelien & Nordeng, Hedvig Marie Egeland (2021). Maternal use of statins in pregnancy: a population based registry study. Full text in Research Archive
• Christensen, Jacob Juel; Bogsrud, Martin P.; Holven, Kirsten B.; Retterstøl, Kjetil; Veierød, Marit B. & Nordeng, Hedvig Marie Egeland (2021). Maternal use of statins in pregnancy: a population-based registry study. Full text in Research Archive

View all works in NVA