Inger Olaug Ottestad

• 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.

• 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
• Paur, Ingvild & Ottestad, Inger Olaug (2025). Key considerations for who, when, why, and how to screen for malnutrition. Current opinion in clinical nutrition and metabolic care. ISSN 1363-1950. 28(5), p. 388–395. doi: 10.1097/MCO.0000000000001144. Full text in Research Archive Show summary

  Purpose of review Confusion and disagreement about malnutrition screening, how, when, why, who to screen, and which screening tool to use, have persisted since the Global Leadership Initiative on Malnutrition (GLIM) established the malnutrition diagnosis in 2019. In this review, we discuss the purpose of malnutrition screening, presents recent validations of screening tools and how the choice of tools affects malnutrition prevalence within the GLIM framework. Recent findings The screening for malnutrition should consider the results of recent validations of screening tools against the GLIM criteria, which reveal variations based on the specific tool, the population, and the setting. Likewise, the prevalence of malnutrition varies with the population and setting, and even how screening tools are applied in the process. Currently, all screening tools exclude patients who meet the GLIM criteria for a malnutrition diagnosis, but the extent of exclusion varies. Summary In this review, we summarize recent prevalence and validation studies on screening tools related to GLIM. We argue that screening tools should align with GLIM malnutrition diagnosis criteria, need to be validated against GLIM, and discuss the requirement that a positive screening result is mandatory for a malnutrition diagnosis.

• Erichsen, Marianne; Solheim, Tora S; Ottestad, Inger; Paur, Ingvild; Sande, Rikka Frøyen & Nygaard, Astrid [Show all 17 contributors for this article] (2025). Parenteral Nutrition in Patients with Incurable Cancer: Exploring the Heterogenous and Non-Randomised Clinical Landscape. Current Oncology. ISSN 1198-0052. 32(11). doi: 10.3390/curroncol32110644. Full text in Research Archive Show summary

  Background: There is an insufficient knowledge base for optimal parenteral nutrition (PN) use for patients with incurable cancer, leading to vague guidelines and varied practices. The aim of the study is to describe the practices and actual outcomes of PN in patients with incurable cancer at Norwegian hospitals. Methods: This multicentre study retrospectively reviewed 507 deceased patients (>18 years) receiving PN between 2011 and 2017. Data were collected from PN initiation until death, and analyses were descriptive. Results: Fifty-one percent had upper and lower gastrointestinal cancers, and the main PN indications were insufficient intake (75%) and gastrointestinal malfunction (47%). Sixty-seven percent received no anticancer treatment. Forty-three (8%) received PN as temporary bridging to anticancer treatment, of whom fifteen (35%) resumed or initiated treatment. The median PN dose corresponded to 53% of estimated energy requirements, and 94% of the patients had complementary energy intake. The most common reason for discontinuation was expected imminent death (47%). While common symptoms during PN were nausea (52%), vomiting (46%), and oedema (37%), 15% reported improved wellbeing. Conclusions: In this real-world cohort, up to 80% of the patients would not meet the eligibility criteria of previous trials due to cancer diagnosis and treatment, gastrointestinal tract function, weight loss criteria or complications such as ascites. This study highlights the heterogeneity in how patients with incurable cancer receive PN, and emphasises the importance of individualised PN treatment, carefully and safely managed to meet the patients’ palliative care situation. Future real-world pragmatic patient-centred protocols bridging the gap between clinical trials and patients in clinical practice are warranted.

• Beichmann, Benedicte; Sollerud, Eli; Warmbrodt, Nicole Sonja; Ottestad, Inger; Paulsen, Mari Mohn & Henriksen, Christine [Show all 7 contributors for this article] (2025). Measured and predicted energy expenditure among patients with distal bowel cancer: Results from the GAIN-project. Clinical Nutrition. ISSN 0261-5614. 53, p. 88–98. doi: 10.1016/j.clnu.2025.08.022. Full text in Research Archive
• Engstad, Martin Kvalvik; Seynnes, Olivier R.; Vesterhus, Ingvild; Hesseberg, Eirik; Fjeldberg, Ken & Carlsen, Monica Hauger [Show all 12 contributors for this article] (2025). Effect of Oral Contraceptive Use on Muscle Hypertrophy Following Strength Training. Scandinavian Journal of Medicine & Science in Sports. ISSN 0905-7188. 35(4). doi: 10.1111/sms.70052. Full text in Research Archive Show summary

  Oral contraceptives (OC) are widely used by women, while their interactions with strength training are yet to be resolved. This study investigated the effects of OC use on muscle hypertrophy and strength adaptation to heavy strength training in young adult women. Fifteen habitual OC users and 17 non-OC users (NOC) with regular menstrual cycles completed ~12 weeks of strength training, which spanned three menstrual cycles for the NOC group. All participants were young, healthy, and strength-untrained. Isometric knee-extensor strength, muscle cross-sectional area of the vastus lateralis (ultrasound imaging), and body composition (DXA) were used to evaluate training adaptations. Blood samples for estradiol and progesterone analyses, dietary registrations, and questionnaires assessing appetite, vitality, motivation, recovery status, and sleep duration were collected during the intervention period. Both groups experienced gains in lean mass and muscle strength. However, the OC group demonstrated a significantly larger increase in arm lean mass (5.5% ± 3.9% [mean ± standard deviation] vs. 2.9% ± 2.8%, p < 0.05) and vastus lateralis cross-sectional area (10.0% ± 4.1% vs. 5.3% ± 4.4%, p < 0.05) compared to the NOC group. Despite these differences, there was no significant group difference in lower body strength gains. Both groups reported similar levels of appetite, dietary intake, vitality, motivation to exercise, and perceived recovery throughout the study, although the OC group slept an average of 42 min longer per day. Our findings suggest that OC use potentiates muscle growth during strength training, although further research is needed to elucidate the underlying mechanisms and long-term effects.

• Dajani, Olav; Philips, Iain; Størkson, Ester Kristine; Balstad, Trude Rakel; Brown, Leo R. & Bye, Asta [Show all 23 contributors for this article] (2025). Oncological and Survival Endpoints in Cancer Cachexia Clinical Trials: Systematic Review 6 of the Cachexia Endpoints Series. Journal of Cachexia, Sarcopenia and Muscle. ISSN 2190-5991. 16(2), p. 1–24. doi: 10.1002/jcsm.13756. Full text in Research Archive
• Balstad, Trude Rakel; Bråtveit, Marianne; Solheim, Tora S; Koteng, Lisa Heide; Bye, Asta & Jakobsen, Rasmus Dahl [Show all 12 contributors for this article] (2024). Validity of dietary intake methods in cancer cachexia. Current opinion in supportive and palliative care. ISSN 1751-4258. 18(3), p. 145–153. doi: 10.1097/SPC.0000000000000709. Full text in Research Archive Show summary

  Purpose of review: Accurate assessment of dietary intake, especially energy and protein intake, is crucial for optimizing nutritional care and outcomes in patients with cancer. Validation of dietary assessment methods is necessary to ensure accuracy, but the validity of these methods in patients with cancer, and especially in those with cancer cachexia, is uncertain. Validating nutritional intake is complex because of the variety of dietary methods, lack of a gold standard method, and diverse validation measures. Here, we review the literature on validations of dietary intake methods in patients with cancer, including those with cachexia, and highlight the gap between current validation efforts and the need for accurate dietary assessment methods in this population. Recent findings: We analyzed eight studies involving 1479 patients with cancer to evaluate the accuracy and reliability of 24-hour recalls, food records, and food frequency questionnaires in estimating energy and protein intake. We discuss validation methods, including comparison with biomarkers, indirect calorimetry, and relative validation of dietary intake methods. Summary: Few have validated dietary intake methods against objective markers in patients with cancer. While food records and 24-hour recalls show potential accuracy for energy and protein intake, this may be compromised in hypermetabolic patients. Additionally, under- and overreporting of intake may be less frequent, and the reliability of urinary nitrogen as a protein intake marker in patients with cachexia needs further investigation. Accurate dietary assessment is important for enhancing nutritional care outcomes in cachexia trials, requiring validation at multiple time points throughout the cancer trajectory.

• Vagnildhaug, Ola Magne; Balstad, Trude Rakel; Ottestad, Inger; Bye, Asta; Greil, Christine & Arends, Jann [Show all 24 contributors for this article] (2024). Appetite and dietary intake endpoints in cancer cachexia clinical trials: Systematic Review 2 of the cachexia endpoints series. Journal of Cachexia, Sarcopenia and Muscle. ISSN 2190-5991. 15, p. 513–535. doi: 10.1002/jcsm.13434. Full text in Research Archive Show summary

  There is no consensus on the optimal endpoint(s) in cancer cachexia trials. Endpoint variation is an obstacle when comparing interventions and their clinical value. The aim of this systematic review was to summarize and evaluate endpoints used to assess appetite and dietary intake in cancer cachexia clinical trials. A search for studies published from 1 January 1990 until 2 June 2021 was conducted using MEDLINE, Embase and Cochrane Central Register of Controlled Trials. Eligible studies examined cancer cachexia treatment versus a comparator in adults with assessments of appetite and/or dietary intake as study endpoints, a sample size ≥40 and an intervention lasting ≥14 days. Reporting was in line with PRISMA guidance, and a protocol was published in PROSPERO (2022 CRD42022276710). This review is part of a series of systematic reviews examining cachexia endpoints. Of the 5975 articles identified, 116 were eligible for the wider review series and 80 specifically examined endpoints of appetite (65 studies) and/or dietary intake (21 studies). Six trials assessed both appetite and dietary intake. Appetite was the primary outcome in 15 trials and dietary intake in 7 trials. Median sample size was 101 patients (range 40–628). Forty-nine studies included multiple primary tumour sites, while 31 studies involved single primary tumour sites (15 gastrointestinal, 7 lung, 7 head and neck and 2 female reproductive organs). The most frequently reported appetite endpoints were visual analogue scale (VAS) and numerical rating scale (NRS) (40%). The appetite item from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30/C15 PAL (38%) and the appetite question from North Central Cancer Treatment Group anorexia questionnaire (17%) were also frequently applied. Of the studies that assessed dietary intake, 13 (62%) used food records (prospective registrations) and 10 (48%) used retrospective methods (24-h recall or dietary history). For VAS/NRS, a mean change of 1.3 corresponded to Hedge's g of 0.5 and can be considered a moderate change. For food records, a mean change of 231 kcal/day or 11 g of protein/day corresponded to a moderate change. Choice of endpoint in cachexia trials will depend on factors pertinent to the trial to be conducted. Nevertheless, from trials assessed and available literature, NRS or EORTC QLQ C30/C15 PAL seems suitable for appetite assessments. Appetite and dietary intake endpoints are rarely used as primary outcomes in cancer cachexia. Dietary intake assessments were used mainly to monitor compliance and are not validated in cachexia populations. Given the importance to cachexia studies, dietary intake endpoints must be validated before they are used as endpoints in clinical trials.

• 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.

• Hjermstad, Marianne Jensen; Jakobsen, Gunnhild; Arends, Jann; Balstad, Trude Rakel; Brown, Leo R. & Bye, Asta [Show all 26 contributors for this article] (2024). Quality of life endpoints in cancer cachexia clinical trials: Systematic review 3 of the cachexia endpoints series. Journal of Cachexia, Sarcopenia and Muscle. ISSN 2190-5991. 15(3), p. 794–815. doi: 10.1002/jcsm.13453. Full text in Research Archive Show summary

  The use of patient-reported outcomes (PROMs) of quality of life (QOL) is common in cachexia trials. Patients' self-report on health, functioning, wellbeing, and perceptions of care, represent important measures of efficacy. This review describes the frequency, variety, and reporting of QOL endpoints used in cancer cachexia clinical trials. Electronic literature searches were performed in Medline, Embase, and Cochrane (1990–2023). Seven thousand four hundred thirty-five papers were retained for evaluation. Eligibility criteria included QOL as a study endpoint using validated measures, controlled design, adults (>18 years), ≥40 participants randomized, and intervention exceeding 2 weeks. The Covidence software was used for review procedures and data extractions. Four independent authors screened all records for consensus. Papers were screened by titles and abstracts, prior to full-text reading. PRISMA guidance for systematic reviews was followed. The protocol was prospectively registered via PROSPERO (CRD42022276710). Fifty papers focused on QOL. Twenty-four (48%) were double-blind randomized controlled trials. Sample sizes varied considerably (n = 42 to 469). Thirty-nine trials (78%) included multiple cancer types. Twenty-seven trials (54%) featured multimodal interventions with various drugs and dietary supplements, 11 (22%) used nutritional interventions alone and 12 (24%) used a single pharmacological intervention only. The median duration of the interventions was 12 weeks (4–96). The most frequent QOL measure was the EORTC QLQ-C30 (60%), followed by different FACIT questionnaires (34%). QOL was a primary, secondary, or exploratory endpoint in 15, 31 and 4 trials respectively, being the single primary in six. Statistically significant results on one or more QOL items favouring the intervention group were found in 18 trials. Eleven of these used a complete multidimensional measure. Adjustments for multiple testing when using multicomponent QOL measures were not reported. Nine trials (18%) defined a statistically or clinically significant difference for QOL, five with QOL as a primary outcome, and four with QOL as a secondary outcome. Correlation statistics with other study outcomes were rarely performed. PROMs including QOL are important endpoints in cachexia trials. We recommend using well-validated QOL measures, including cachexia-specific items such as weight history, appetite loss, and nutritional intake. Appropriate statistical methods with definitions of clinical significance, adjustment for multiple testing and few co-primary endpoints are encouraged, as is an understanding of how interventions may relate to changes in QOL endpoints. A strategic and scientific-based approach to PROM research in cachexia trials is warranted, to improve the research base in this field and avoid the use of QOL as supplementary measures.

• Koteng, Lisa Heide; Sand, Kari; Paur, Ingvild; Bye, Asta; Ervik, Bente & Solheim, Tora S [Show all 8 contributors for this article] (2024). Exploring the barriers to diagnosing malnutrition in patients with cancer: A study on oncologists' perspectives. Clinical Nutrition Open Science. 58, p. 289–301. doi: 10.1016/j.nutos.2024.10.001. Full text in Research Archive Show summary

  Background and aim Patients with cancer are at high risk of malnutrition, yet relevant ICD-10 codes for malnutrition are underutilized in cancer clinics. Understanding oncologists' perspectives is crucial for optimizing malnutrition diagnosis codes and enhancing nutritional practices to improve patient care. This study aims to explore oncologists' perspectives on the use and feasibility of the ICD-10 codes for malnutrition. Methods A qualitative study was conducted, consisting of four focus group interviews with oncologists (n=14) from three Norwegian hospitals. A semi-structured interview guide, covering five main topics, guided the discussions. Results Few oncologists were familiar with the malnutrition diagnosis codes. The codes were considered inapplicable in clinical practice, partly due to complex diagnostic criteria. None used the codes systematically, instead relying on inquiries about patients' weight, weight loss, food intake, and appetite. Oncologists prioritized identifying patients in need of nutritional treatment, considering diagnosis codes unnecessary for providing quality care. Proposals for increased code utilization included economic incentives, enhanced collaboration with clinical dietitians, and digital systems for automated coding. Conclusion The oncologists expressed that they prevent and treat malnutrition in patients with cancer, but not systematically. They do not utilize ICD-10 codes for malnutrition, citing both complex diagnostic criteria and the codes’ lack of relevance to nutritional treatment as limiting factors.

• Ottestad, Inger; Thoresen, Lene; Tangvik, Randi Julie; Fjeldstad, Siv Hilde; Authen, Mina Marie & Følstad, Sandra [Show all 18 contributors for this article] (2024). Inadequate nutritional care for malnourished patients in four university hospitals – The QuaNuT study. Clinical Nutrition Open Science. 54, p. 63–77. doi: 10.1016/j.nutos.2024.01.002. Full text in Research Archive Show summary

  Background & Aims Adequate nutritional care to malnourished patients is described as a human right, and recommendations from nutritional care guidelines are legally binding in Norway. The primary objective of this study was to investigate nutritional care in malnourished hospitalized patients. We also wanted to describe the association between malnutrition and length of stay (LOS), readmission, comorbidity and mortality. Methods In a cross-sectional, multi-center and quality assurance study, inpatients from four university hospitals across all regional health authorities in Norway were included. The hospital's nutritional care during admission was evaluated according to current malnutrition guidelines. Malnutrition risk screening, assessment for diagnosis and grading severity of malnutrition were performed with Nutritional risk screening 2002 (NRS-2002) and the Global Leadership Initiative on malnutrition (GLIM) criteria. Medical records were reviewed to collect data on nutritional support during admission, malnutrition coding, LOS, readmission, comorbidity and 30-days survival after hospital admission. Results In our mixed inpatient population (n 442, mean age 61 years, 53 % women), 42 % were not adequately screened for risk of malnutrition at hospital admission. Among the 29 % of malnourished patients, only 36 % had documented nutritional support in the medical records, and a malnutrition diagnosis was registered for only 30 %. Malnutrition was associated with LOS, increased comorbidity and reduced 30-day survival. Conclusion In this study across all Norwegian regional health authorities, we found a high malnutrition rate and the nutritional care in relation to malnutrition diverged from national and international established guidelines and the framework of national laws and legislation. The findings raise concerns regarding patient safety and potential for improved nutritional care as a human right. Although malnutrition was associated with longer length of hospital stay, comorbidity and reduced 30-day survival, this study does not establish causal relationships.

• Brown, Leo R.; Sousa, Mariana S.; Yule, Michael S.; Baracos, Vickie E.; McMillan, Donald C. & Arends, Jann [Show all 24 contributors for this article] (2024). Body weight and composition endpoints in cancer cachexia clinical trials: Systematic Review 4 of the cachexia endpoints series. Journal of Cachexia, Sarcopenia and Muscle. ISSN 2190-5991. 15(3), p. 816–852. doi: 10.1002/jcsm.13478. Full text in Research Archive Show summary

  Significant variation exists in the outcomes used in cancer cachexia trials, including measures of body composition, which are often selected as primary or secondary endpoints. To date, there has been no review of the most commonly selected measures or their potential sensitivity to detect changes resulting from the interventions being examined. The aim of this systematic review is to assess the frequency and diversity of body composition measures that have been used in cancer cachexia trials. MEDLINE, Embase and Cochrane Library databases were systematically searched between January 1990 and June 2021. Eligible trials examined adults (≥18 years) who had received an intervention aiming to treat or attenuate the effects of cancer cachexia for >14 days. Trials were also of a prospective controlled design and included body weight or at least one anthropometric, bioelectrical or radiological endpoint pertaining to body composition, irrespective of the modality of intervention (e.g., pharmacological, nutritional, physical exercise and behavioural) or comparator. Trials with a sample size of <40 patients were excluded. Data extraction used Covidence software, and reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. This review was prospectively registered (PROSPERO: CRD42022276710). A total of 84 clinical trials, comprising 13 016 patients, were eligible for inclusion. Non-small-cell lung cancer and pancreatic cancer were studied most frequently. The majority of trial interventions were pharmacological (52%) or nutritional (34%) in nature. The most frequently reported endpoints were assessments of body weight (68 trials, n = 11 561) followed by bioimpedance analysis (BIA)-based estimates (23 trials, n = 3140). Sixteen trials (n = 3052) included dual-energy X-ray absorptiometry (DEXA)-based endpoints, and computed tomography (CT) body composition was included in eight trials (n = 841). Discrepancies were evident when comparing the efficacy of interventions using BIA-based estimates of lean tissue mass against radiological assessment modalities. Body weight, BIA and DEXA-based endpoints have been most frequently used in cancer cachexia trials. Although the optimal endpoints cannot be determined from this review, body weight, alongside measurements from radiological body composition analysis, would seem appropriate. The choice of radiological modality is likely to be dependent on the trial setting, population and intervention in question. CT and magnetic resonance imaging, which have the ability to accurately discriminate tissue types, are likely to be more sensitive and provide greater detail. Endpoints are of particular importance when aligned with the intervention's mechanism of action and/or intended patient benefit.

• Bålsrud, Pia; Ulven, Stine Marie; Christensen, Jacob J.; Ottestad, Inger & Holven, Kirsten Bjørklund (2024). Inflammatory markers and frailty in home-dwelling elderly, a cross-sectional study. BMC Geriatrics. 24(1), p. 1–11. doi: 10.1186/s12877-024-04690-2. Full text in Research Archive Show summary

  Background Low-grade, chronic inflammation during ageing, (“inflammageing”), is suggested to be involved in the development of frailty in older age. However, studies on the association between frailty, using the frailty index definition, and inflammatory markers are limited. The aim of this study was to investigate the relationship between inflammatory markers and frailty index (FI) in older, home-dwelling adults. Method Home-dwelling men and women aged ≥ 70 years old, living in South-East Norway were recruited and included in a cross-sectional study. The FI used in the current study was developed according to Rockwood’s frailty index and included 38 variables, resulting in an FI score between 0 and 1 for each participant. Circulating inflammatory markers (IL-6, CRP, IGF-1, cystatin C, cathepsin S, and glycoprotein Acetyls) were analyzed from non-fasting blood samples using ELISA. Whole-genome PBMC transcriptomics was used to study the association between FI score and inflammation. Results The study population comprised 403 elderly (52% women), with a median age of 74 years and a mean BMI of 26.2 kg/m2. The mean FI score for the total group was 0.15 (range 0.005–0.56). The group was divided into a frail group (FI score ≥ 0.25) and non-frail group. After adjusting for BMI, age, sex, and smoking in the whole group, IL-6, cathepsin S, cystatin C, and Gp-acetyls remained significant associated to FI score (IL-6: 0.002, 95% CI: 0.001, 0.002, cathepsin S: 6.7e-06, 95% CI 2.44e-06, 0.00001, cystatin C: 0.004, 95% CI: 0.002, 0.006, Gp- Acetyls: 0.09, 95% CI: 0.05, 0.13, p < 0.01 for all), while CRP and IGF-1 were not (0.0003, 95% CI: -00001, 0.0007, p = 0.13, (-1.27e-06), 95% CI: (-0.0003), 0.0003, p = 0.99). There was a significant association between FI score and inflammatory markers, and FI score and monocyte-specific gene expression. Conclusions We found an association between FI score and inflammatory markers, and between FI score and monocyte-specific gene expression among elderly subjects above 70 years of age. Whether inflammation is a cause or consequence of frailty and whether the progression of frailty can be attenuated by reducing inflammation remains to be clarified.

• Yule, Michael S.; Thompson, Joshua; Leesahatsawat, Khachonphat; Sousa, Mariana S.; Anker, Stefan D. & Arends, Jann [Show all 26 contributors for this article] (2024). Biomarker endpoints in cancer cachexia clinical trials: Systematic Review 5 of the cachexia endpoint series. Journal of Cachexia, Sarcopenia and Muscle. ISSN 2190-5991. 15(3), p. 853–867. doi: 10.1002/jcsm.13491. Full text in Research Archive Show summary

  Regulatory agencies require evidence that endpoints correlate with clinical benefit before they can be used to approve drugs. Biomarkers are often considered surrogate endpoints. In cancer cachexia trials, the measurement of biomarkers features frequently. The aim of this systematic review was to assess the frequency and diversity of biomarker endpoints in cancer cachexia trials. A comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990–2023) was completed. Eligible trials met the following criteria: adults (≥18 years), prospective design, more than 40 participants, use of a cachexia intervention for more than 14 days and use of a biomarker(s) as an endpoint. Biomarkers were defined as any objective measure that was assayed from a body fluid, including scoring systems based on these assays. Routine haematology and biochemistry to monitor intervention toxicity were not considered. Data extraction was performed using Covidence, and reporting followed PRISMA guidance (PROSPERO: CRD42022276710). A total of 5975 studies were assessed, of which 52 trials (total participants = 6522) included biomarkers as endpoints. Most studies (n = 29, 55.7%) included a variety of cancer types. Pharmacological interventions (n = 27, 51.9%) were most evaluated, followed by nutritional interventions (n = 20, 38.4%). Ninety-nine different biomarkers were used across the trials, and of these, 96 were assayed from blood. Albumin (n = 29, 55.8%) was assessed most often, followed by C-reactive protein (n = 22, 42.3%), interleukin-6 (n = 16, 30.8%) and tumour necrosis factor-α (n = 14, 26.9%), the latter being the only biomarker that was used to guide sample size calculations. Biomarkers were explicitly listed as a primary outcome in six trials. In total, 12 biomarkers (12.1% of 99) were used in six trials or more. Insulin-like growth factor binding protein 3 (IGFBP-3) and insulin-like growth factor 1 (IGF-1) levels both increased significantly in all three trials in which they were both used. This corresponded with a primary outcome, lean body mass, and was related to the pharmacological mechanism. Biomarkers were predominately used as exploratory rather than primary endpoints. The most commonly used biomarker, albumin, was limited by its lack of responsiveness to nutritional intervention. For a biomarker to be responsive to change, it must be related to the mechanism of action of the intervention and/or the underlying cachexia process that is modified by the intervention, as seen with IGFBP-3, IGF-1 and anamorelin. To reach regulatory approval as an endpoint, the relationship between the biomarker and clinical benefit must be clarified.

• Sousa, Ana Rita Sequeira de; Ottestad, Inger; Gjevestad, Gyrd Omholt; Holven, Kirsten Bjørklund; Ulven, Stine Marie & Christensen, Jacob J. (2023). Associations between PBMC whole genome transcriptome, muscle strength, muscle mass, and physical performance in healthy home-dwelling older women. GeroScience. ISSN 2509-2715. 45, p. 3175–3186. doi: 10.1007/s11357-023-00819-0. Full text in Research Archive Show summary

  Abstract Increasing age is accompanied by many changes, including declining functional skeletal muscle health and immune dysfunction. Peripheral blood mononuclear cells (PBMCs) are circulating cells that assemble an immune response, but their whole genome transcriptome has not been studied in the context of age-related muscle health. Consequently, this article explored associations between three muscle variables indicative of functional muscle health — maximum handgrip strength (muscle strength), appendicular skeletal muscle mass index (ASMI, muscle mass), and gait speed (physical performance) — and two groups of bioinformatics-generated PBMC gene expression features (gene expression–estimated leukocyte subset proportions and gene clusters). We analyzed cross-sectional data from 95 home-dwelling healthy women ≥ 70 years, using “cell-type identification by estimating relative subsets of RNA transcripts” (CIBERSORT) to estimate leukocyte subset proportions and “weighted correlation network analysis” (WGCNA) to generate gene clusters. Associations were studied using linear regression models and relevant gene clusters were subjected to gene set enrichment analysis using gene ontology. Gait speed and ASMI associated with CIBERSORT-estimated monocyte proportions ( β  =  − 0.090, 95% CI = (− 0.146, − 0.034), p -value = 0.002 for gait speed, and β  =  − 0.206, 95% CI = (− 0.385, − 0.028), p -value = 0.024 for ASMI), and gait speed associated with CIBERSORT-estimated M2 macrophage proportions ( β  =  − 0.026, 95% CI = (− 0.043, − 0.008), p -value = 0.004). Furthermore, maximum handgrip strength associated with nine WGCNA gene clusters, enriched in processes related to immune function and skeletal muscle cells ( β in the range − 0.007 to 0.008, p -values &lt; 0.05). These results illustrate interactions between skeletal muscle and the immune system, supporting the notion that age-related functional muscle health and the immune system are closely linked.

• McDonald, James; Sayers, Judith; Anker, Stefan D.; Arends, Jann; Balstad, Trude Rakel & Baracos, Vickie [Show all 29 contributors for this article] (2023). Physical function endpoints in cancer cachexia clinical trials: Systematic Review 1 of the cachexia endpoints series. Journal of Cachexia, Sarcopenia and Muscle. ISSN 2190-5991. doi: 10.1002/jcsm.13321. Full text in Research Archive Show summary

  In cancer cachexia trials, measures of physical function are commonly used as endpoints. For drug trials to obtain regulatory approval, efficacy in physical function endpoints may be needed alongside other measures. However, it is not clear which physical function endpoints should be used. The aim of this systematic review was to assess the frequency and diversity of physical function endpoints in cancer cachexia trials. Following a comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990–2021), records were retrieved. Eligible trials met the following criteria: adults (≥18 years), controlled design, more than 40 participants, use of a cachexia intervention for more than 14 days and use of a physical function endpoint. Physical function measures were classified as an objective measure (hand grip strength [HGS], stair climb power [SCP], timed up and go [TUG] test, 6-min walking test [6MWT] and short physical performance battery [SPPB]), clinician assessment of function (Karnofsky Performance Status [KPS] or Eastern Cooperative Oncology Group-Performance Status [ECOG-PS]) or patient-reported outcomes (physical function subscale of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaires [EORTC QLQ-C30 or C15]). Data extraction was performed using Covidence and followed PRISMA guidance (PROSPERO registration: CRD42022276710). A total of 5975 potential studies were examined and 71 were eligible. Pharmacological interventions were assessed in 38 trials (54%). Of these, 11 (29%, n = 1184) examined megestrol and 5 (13%, n = 1928) examined anamorelin; nutritional interventions were assessed in 21 trials (30%); and exercise-based interventions were assessed in 6 trials (8%). The remaining six trials (8%) assessed multimodal interventions. Among the objective measures of physical function (assessed as primary or secondary endpoints), HGS was most commonly examined (33 trials, n = 5081) and demonstrated a statistically significant finding in 12 (36%) trials (n = 2091). The 6MWT was assessed in 12 trials (n = 1074) and was statistically significant in 4 (33%) trials (n = 403), whereas SCP, TUG and SPPB were each assessed in 3 trials. KPS was more commonly assessed than the newer ECOG-PS (16 vs. 9 trials), and patient-reported EORTC QLQ-C30 physical function was reported in 25 trials. HGS is the most commonly used physical function endpoint in cancer cachexia clinical trials. However, heterogeneity in study design, populations, intervention and endpoint selection make it difficult to comment on the optimal endpoint and how to measure this. We offer several recommendations/considerations to improve the design of future clinical trials in cancer cachexia.

• Øhman, Elisabeth Adolfsen; Fossli, Maria; Ottestad, Inger; Holven, Kirsten Bjørklund; Ulven, Stine Marie & Løland, Beate Fossum [Show all 7 contributors for this article] (2023). Dietary treatment postpartum in women with obesity reduces weight and prevents weight gain: a randomised controlled trial. BMC Pregnancy and Childbirth. 23. doi: 10.1186/s12884-023-05976-w. Full text in Research Archive Show summary

  Background Women with pre-pregnancy obesity have an increased risk of retaining or gaining weight postpartum and may benefit from weight loss treatment. However, evidence is lacking for weight loss strategies in women with BMIs in the higher obesity classes. A dietary treatment for postpartum weight loss resulted in a 10% weight reduction in lactating women with a mean BMI of 30 kg/m2. We aimed to examine the effects of this dietary treatment on changes in weight, markers of lipid and glucose metabolism, waist and hip circumference and postpartum weight retention (PPWR) in postpartum women with higher BMIs than tested previously. Methods At baseline, approximately 8 weeks postpartum, 29 women with a mean (SD) BMI = 40.0 (5.2) kg/m2 were randomised to a 12-week dietary treatment (n 14) or to a control treatment (n 15). Measurements were made at baseline and after 3 and 12 months. Data was analysed using mixed model. Results The mean weight change in the diet group was -2.3 (3.1) kg compared to 1.7 (3.1) kg in the control group after 3 months (P = 0.003) and -4.2 (5.6) kg compared to 4.8 (11.8) kg in the control group after 12 months (P = 0.02). The dietary treatment led to reduced waist circumference (P < 0.04) and PPWR (P < 0.01) compared to the control treatment at both time points. The treatment lowered fasting blood glucose at 12 months (P = 0.007) as the only effect on markers of lipid and glucose metabolism. Conclusion The dietary treatment postpartum reduced weight and prevented weight retention or weight gain in women with obesity. Trial registration The trial was retrospectively registered at ClinicalTrials.gov (NCT03579667) 06/07/2018. Graphical Abstract In a randomised, controlled trial, 29 postpartum women with obesity were allocated to a dietary treatment or a control treatment. The dietary treatment reduced weight and prevented postpartum weight retention or weight gain after 12 months. Reference: Adapted from “Randomized, Placebo-Controlled, Parallel Study Design (2 Arms, Graphical)”, by BioRender.com (2022). Retrieved from https://app.biorender.com/biorender-templates .

• Rundblad, Amanda; Christensen, Jacob J.; Hustad, Kristin Solheim; Bastani, Nasser Ezzatkhah; Ottestad, Inger & Holven, Kirsten Bjørklund [Show all 7 contributors for this article] (2023). Associations between dietary intake and glucose tolerance in clinical and metabolomics-based metabotypes. Genes & Nutrition. ISSN 1555-8932. 18(3). doi: 10.1186/s12263-023-00721-6. Full text in Research Archive Show summary

  Background Metabotyping is a novel concept to group metabolically similar individuals. Different metabotypes may respond differently to dietary interventions; hence, metabotyping may become an important future tool in precision nutrition strategies. However, it is not known if metabotyping based on comprehensive omic data provides more useful identification of metabotypes compared to metabotyping based on only a few clinically relevant metabolites. Aim This study aimed to investigate if associations between habitual dietary intake and glucose tolerance depend on metabotypes identified from standard clinical variables or comprehensive nuclear magnetic resonance (NMR) metabolomics. Methods We used cross-sectional data from participants recruited through advertisements aimed at people at risk of type 2 diabetes mellitus (n = 203). Glucose tolerance was assessed with a 2-h oral glucose tolerance test (OGTT), and habitual dietary intake was recorded with a food frequency questionnaire. Lipoprotein subclasses and various metabolites were quantified with NMR spectroscopy, and plasma carotenoids were quantified using high-performance liquid chromatography. We divided participants into favorable and unfavorable clinical metabotypes based on established cutoffs for HbA1c and fasting and 2-h OGTT glucose. Favorable and unfavorable NMR metabotypes were created using k-means clustering of NMR metabolites. Results While the clinical metabotypes were separated by glycemic variables, the NMR metabotypes were mainly separated by variables related to lipoproteins. A high intake of vegetables was associated with a better glucose tolerance in the unfavorable, but not the favorable clinical metabotype (interaction, p = 0.01). This interaction was confirmed using plasma concentrations of lutein and zeaxanthin, objective biomarkers of vegetable intake. Although non-significantly, the association between glucose tolerance and fiber intake depended on the clinical metabotypes, while the association between glucose tolerance and intake of saturated fatty acids and dietary fat sources depended on the NMR metabotypes. Conclusion Metabotyping may be a useful tool to tailor dietary interventions that will benefit specific groups of individuals. The variables that are used to create metabotypes will affect the association between dietary intake and disease risk.

• Hustad, Kristin Solheim; Ottestad, Inger; Olsen, Thomas; Sæther, Thomas; Ulven, Stine Marie & Holven, Kirsten Bjørklund (2022). Salmon fish protein supplement increases serum vitamin B12 and selenium concentrations: secondary analysis of a randomised controlled trial. European Journal of Nutrition. ISSN 1436-6207. 61(6), p. 3085–3093. doi: 10.1007/s00394-022-02857-4. Full text in Research Archive Show summary

  Abstract Purpose The main aim of the present study was to examine the effect of a fish protein supplement made from by-products from production of Atlantic salmon, on blood concentration of micronutrients. Methods We conducted an 8-week double-blind parallel-group randomised controlled trial. In total, 88 adults were randomised to a salmon fish protein supplement or placebo, and 74 participants were included in the analysis of vitamin D, omega-3, vitamin B12, selenium, folate, zinc, homocysteine and mercury. Results During the intervention period, geometric mean (GSD) of serum vitamin B12 concentrations increased from 304 (1.40) to 359 (1.42) pmol/L in the fish protein group ( P vs. controls = 0.004) and mean (SD) serum selenium increased from 1.18 (0.22) to 1.30 (0.20) μmol/L ( P vs. controls = 0.002). The prevalence of low vitamin B12 status (B12 &lt; 148–221 &gt; pmol/L) decreased from 15.4 to 2.6% in the fish protein group, while increasing from 5.9 to 17.6% in the placebo group ( P  = 0.045). There was no difference between the groups in serum levels of the other micronutrients measured. Conclusion Including a salmon fish protein supplement in the daily diet for 8 weeks, increases serum vitamin B12 and selenium concentrations. From a sustainability perspective, by-products with high contents of micronutrients and low contents of contaminants, could be a valuable dietary supplement or food ingredient in populations with suboptimal intake. Trail Registration The study was registered at ClinicalTrials.gov (ID: NCT03764423) on June 29th 2018.

• Canet, Francisco; Christensen, Jacob J.; Victor, Victor M.; Hustad, Kristin Solheim; Ottestad, Inger & Rundblad, Amanda [Show all 11 contributors for this article] (2022). Glycated proteins, glycine, acetate, and monounsaturated fatty acids may act as new biomarkers to predict the progression of type 2 diabetes: Secondary analyses of a randomized controlled trial. Nutrients. 14(23), p. 1–19. doi: 10.3390/nu14235165. Full text in Research Archive Show summary

  Food protein or food-derived peptides may regulate blood glucose levels; however, studies have shown inconsistent results. The aim of the present study was to characterize subgroups of individuals with increased risk of type 2 diabetes (T2D) and to investigate the cardiometabolic effects of fish protein in the same subgroups. We first divided participants into high insuliniAUC and low insuliniAUC subjects based on their insulin incremental area under the curve (iAUC) levels after a 2 h oral glucose tolerance test (OGTT), and secondly based on whether they had received 5.2 g salmon fish protein or placebo for 8 weeks, in a previously conducted randomized controlled trial (RCT). We then profiled these groups by analyzing plasma metabolomics and peripheral blood mononuclear cell (PBMC) gene expression. Compared to the low insuliniAUC group, the high insuliniAUC group had higher plasma concentrations of monounsaturated fatty acids (MUFAs) and glycated proteins (GlycA) and lower concentrations of glycine and acetate. After intervention with fish protein compared to placebo, however, only acetate was significantly increased in the low insuliniAUC group. In conclusion, we identified metabolic biomarkers known to be associated with T2D; also, intervention with fish protein did not affect cardiometabolic risk markers in subgroups with increased risk of T2D.

• Hustad, Kristin Solheim; Ottestad, Inger Olaug; Hjorth, Marit; Dalen, Knut Tomas; Sæther, Thomas & Sheikh, Navida Akhter [Show all 9 contributors for this article] (2021). No effect of salmon fish protein on 2-h glucose in adults with increased risk of type 2 diabetes: a randomised controlled trial. British Journal of Nutrition. ISSN 0007-1145. 126(9), p. 1304–1313. doi: 10.1017/S0007114521000040. Full text in Research Archive Show summary

  Abstract The association between fish consumption and decreased risk of CVD is well documented. However, studies on health effects of fish consumption suggest that other components than n -3 PUFA have beneficial cardiometabolic effects, including effects on glucose metabolism. The aim of the present study was to investigate effects of salmon fish protein on cardiometabolic risk markers in a double-blind, randomised controlled parallel trial. We hypothesised that daily intake of a salmon fish protein supplement for 8 weeks would improve glucose tolerance in persons with increased risk of type 2 diabetes mellitus (T2DM). Our primary outcome measure was serum glucose (s-glucose) 2 h after a standardised oral glucose tolerance test. In total, eighty-eight adults with elevated s-glucose levels were randomised to 7·5 g of salmon fish protein/d or placebo, and seventy-four participants were included in the analysis. We found no significant effect of salmon fish protein supplementation on our primary outcome or other markers related to glucose tolerance, serum lipids, weight or blood pressure compared with placebo. The present study does not support the hypothesis that daily intake of a salmon fish protein supplement for 8 weeks improves glucose tolerance in persons with increased risk of T2DM.

• Nordengen, Anne Lene; Øyri, Linn Kristin Lie; Ulven, Stine Marie; Raastad, Truls; Holven, Kirsten Bjørklund & Ottestad, Inger Olaug (2021). Comparison of methods to identify individuals with obesity at increased risk of functional impairment among a population of home-dwelling older adults. British Journal of Nutrition. ISSN 0007-1145. doi: 10.1017/S0007114521004128. Full text in Research Archive Show summary

  Obesity is associated with increased muscle mass and muscle strength. Methods taking into account the total body mass to reveal obese older individuals at increased risk of functional impairment are needed. Therefore, we aimed to detect methods to identify obese older adults at increased risk of functional impairment. Home-dwelling older adults (n 417, ≥ 70 years of age) were included in this cross-sectional study. Sex-specific cut-off points for two obesity phenotypes (waist circumference (WC) and body fat mass (FM %)) were used to divide women and men into obese and non-obese groups, and within-sex comparisons were performed. Obese women and men, classified by both phenotypes, had similar absolute handgrip strength (HGS) but lower relative HGS (HGS/total body mass) (P < 0·001) than non-obese women and men, respectively. Women with increased WC and FM %, and men with increased WC had higher appendicular skeletal muscle mass (P < 0·001), lower muscle quality (HGS/upper appendicular muscle mass) (P < 0·001), and spent longer time on the stair climb test and the repeated sit-to-stand test (P < 0·05) than non-obese women and men, respectively. Absolute muscle strength was not able to discriminate between obese and non-obese older adults. However, relative muscle strength in particular, but also muscle quality and physical performance tests, where the total body mass was taken into account or served as an extra load, identified obese older adults at increased risk of functional impairment. Prospective studies are needed to determine clinically relevant cut-off points for relative HGS in particular.

• Milić, Mirta; Ceppi, Marcello; Bruzzone, Marco; Azqueta, Amaya; Brunborg, Gunnar & Godschalk, Roger [Show all 90 contributors for this article] (2021). The hCOMET project: International database comparison of results with the comet assay in human biomonitoring. Baseline frequency of DNA damage and effect of main confounders. Mutation research. Reviews in mutation research. ISSN 1383-5742. 787. doi: 10.1016/j.mrrev.2021.108371. Full text in Research Archive Show summary

  The alkaline comet assay, or single cell gel electrophoresis, is one of the most popular methods for assessing DNA damage in human population. One of the open issues concerning this assay is the identification of those factors that can explain the large inter-individual and inter-laboratory variation. International collaborative initiatives such as the hCOMET project - a COST Action launched in 2016 - represent a valuable tool to meet this challenge. The aims of hCOMET were to establish reference values for the level of DNA damage in humans, to investigate the effect of host factors, lifestyle and exposure to genotoxic agents, and to compare different sources of assay variability. A database of 19,320 subjects was generated, pooling data from 105 studies run by 44 laboratories in 26 countries between 1999 and 2019. A mixed random effect log-linear model, in parallel with a classic meta-analysis, was applied to take into account the extensive heterogeneity of data, due to descriptor, specimen and protocol variability. As a result of this analysis interquartile intervals of DNA strand breaks (which includes alkali-labile sites) were reported for tail intensity, tail length, and tail moment (comet assay descriptors). A small variation by age was reported in some datasets, suggesting higher DNA damage in oldest age-classes, while no effect could be shown for sex or smoking habit, although the lack of data on heavy smokers has still to be considered. Finally, highly significant differences in DNA damage were found for most exposures investigated in specific studies. In conclusion, these data, which confirm that DNA damage measured by the comet assay is an excellent biomarker of exposure in several conditions, may contribute to improving the quality of study design and to the standardization of results of the comet assay in human populations.

• Nesse, Siri Halland; Ottestad, Inger; Winkvist, Anna; Bertz, Fredrik; Ellegård, Lars & Brekke, Hilde Kristin (2020). Predictive equations for estimating resting energy expenditure in women with overweight and obesity at three postpartum stages. Journal of Nutritional Science (JNS). 9. doi: 10.1017/jns.2020.16. Full text in Research Archive Show summary

  Abstract The objective was to investigate which predictive equations provide the best estimates of resting energy expenditure (REE) in postpartum women with overweight and obesity. Lactating women with overweight or obesity underwent REE measurement by indirect calorimetry, and fat-free mass (FFM) was assessed by dual-energy X-ray absorptiometry at three postpartum stages. Predictive equations based on body weight and FFM were obtained from the literature. Performance of the predictive equations were analysed as the percentage of women whose REE was accurately predicted, defined as a predicted REE within ±10 % of measured REE. REE data were available for women at 10 weeks ( n 71), 24 weeks ( n 64) and 15 months ( n 57) postpartum. Thirty-six predictive equations (twenty-five weight-based and eleven FFM-based) were validated. REE was accurately predicted in ≥80 % of women at all postpartum visits by six predictive equations (two weight-based and four FFM-based). The weight-based equation with the highest performance was that of Henry (weight, height, age 30–60 years) (Henry WH30−60 ), with an overall mean of 83 % accurate predictions. The Henry WH30−60 equation was highly suitable for predicting REE at all postpartum visits (irrespective of the women's actual age), and the performance was sustained across changes in weight and lactation status. No FFM-based equation was remarkably superior to Henry WH30−60 for the total postpartum period.

• Hustad, Solheim Kristin; Rundblad, Amanda; Ottestad, Inger; Christensen, Jacob J.; Holven, Kirsten Bjørklund & Ulven, Stine Marie (2020). Comprehensive lipid and metabolite profiling in healthy adults with low and high consumption of fatty fish: A cross-sectional study. British Journal of Nutrition. ISSN 0007-1145. p. 1–9. doi: 10.1017/S0007114520002305. Full text in Research Archive Show summary

  Abstract Fish consumption is associated with reduced risk of CVD, which may be partly mediated by alterations in plasma lipids, such as HDL-cholesterol. However, comprehensive analyses of associations between fatty fish consumption and lipoprotein subclass profile are limited and show inconsistent results. Therefore, the aim of the present exploratory study was to investigate the association between fatty fish consumption and lipoprotein subclass particle concentrations and composition, with an emphasis on HDL. We performed a comprehensive plasma metabolite profiling in 517 healthy adults, using a targeted high-throughput NMR spectroscopy platform. The participants were divided into tertiles based on consumption of fatty fish, reported through a validated FFQ. We compared the concentration of metabolites between the participants in the lowest and highest tertiles of fatty fish consumption. We show that high consumers of fatty fish (&gt;223 g/week, median intake 294 g/week) had higher particle concentrations and content of total lipids, free cholesterol and phospholipids in large and extra-large HDL particles and higher content of total cholesterol, cholesteryl esters and TAG in large HDL particles than low consumers (&lt;107 g/week, median intake 58 g/week). Using fatty fish consumption as a continuous variable, we found that fatty fish consumption was associated with lower levels of the inflammation marker glycoprotein acetyls. In conclusion, high consumers of fatty fish seem to have a more favourable HDL-cholesterol-related lipoprotein profile and anti-inflammatory phenotype than low consumers of fatty fish. Thus, these data support the current Norwegian dietary recommendations for fish consumption regarding CVD risk.

• Ulven, Stine Marie; Christensen, Jacob J.; Nygård, Ottar; Svardal, Asbjørn M.; Leder, Lena & Ottestad, Inger [Show all 14 contributors for this article] (2019). Using metabolic profiling and gene expression analyses to explore molecular effects of replacing saturated fat with polyunsaturated fat-a randomized controlled dietary intervention study. American Journal of Clinical Nutrition. ISSN 0002-9165. 109(5), p. 1239–1250. doi: 10.1093/ajcn/nqy356. Full text in Research Archive Show summary

  Background: Replacing dietary saturated fatty acids (SFAs) with polyunsaturated fatty acids (PUFA) reduces the plasma low-density lipoprotein (LDL) cholesterol and subsequently the risk of cardiovascular disease. However, beyond changes in LDL cholesterol, we lack a complete understanding of the physiologic alterations that occur when improving dietary fat quality. Objectives: The aim of this study was to gain knowledge of metabolic alterations paralleling improvements in the fat quality of the diet. Methods: We recently conducted an 8-wk, double-blind, randomized controlled trial replacing SFAs with PUFAs in healthy subjects with moderate hypercholesterolemia (n = 99). In the present substudy, we performed comprehensive metabolic profiling with multiple platforms (both nuclear magnetic resonance- and mass spectrometry-based technology) (n = 99), and analyzed peripheral blood mononuclear cell gene expression (n = 95) by quantitative real-time polymerase chain reaction. Results: A large number of lipoprotein subclasses, myristoylcarnitine and palmitoylcarnitine, and kynurenine were reduced when SFAs were replaced with PUFAs. In contrast, bile acids, proprotein convertase subtilisin/kexin type 9, acetate, and acetoacetate were increased by the intervention. Some amino acids were also altered by the intervention. The mRNA levels of LXRA and LDLR were increased, in addition to several liver X receptor α target genes and genes involved in inflammation, whereas the mRNA levels of UCP2 and PPARD were decreased in peripheral blood mononuclear cells after replacing SFAs with PUFAs. Partial least squares-discriminant analysis showed that the 30 most important variables that contributed to class separation spanned all classes of biomarkers, and was in accordance with the univariate analysis. Conclusions: Applying metabolomics in randomized controlled dietary intervention trials has the potential to extend our knowledge of the biological and molecular effects of dietary fat quality. This study was registered at clinicaltrials.gov as NCT 01679496.

• Rundblad, Amanda; Larsen, Sunniva; Myhrstad, Mari; Ottestad, Inger; Thoresen, Magne & Holven, Kirsten Bjørklund [Show all 7 contributors for this article] (2019). Differences in peripheral blood mononuclear cell gene expression and triglyceride composition in lipoprotein subclasses in plasma triglyceride responders and non-responders to omega-3 supplementation. Genes & Nutrition. ISSN 1555-8932. 14(10), p. 1–13. doi: 10.1186/s12263-019-0633-y. Full text in Research Archive Show summary

  Background:Intake of the marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)reduces fasting triglyceride (TG) levels and may thereby lower cardiovascular disease risk. However, there are largeinter-individual differences in the TG-lowering effect of omega-3 supplementation. Genotype differences partly explainthis variation, but gene-environment interactions leading to gene expression differences may also be important. In thisstudy, we aimed to investigate baseline differences and differences in the change in peripheral blood mononuclear cell(PBMC) gene expression and lipoprotein subclass TG levels between TG responders and non-responders to omega-3fatty acid supplementation.Methods:In a previous randomized controlled trial, healthy normotriglyceridemic subjects (n= 35, 71% women)received 1.6 g EPA + DHA/day for 7 weeks. In this exploratory sub-study, we defined TG responders as subjects havinga TG reduction beyond the 20% day-to-day variation and non-responders as having a TG change between−20% and+ 20% after omega-3 supplementation. PBMC gene expression was measured using microarray, and lipoproteinsubclasses were measured using nuclear magnetic resonance spectroscopy.Results:Eight subjects were defined as responders with a median TG reduction of 37%, and 16 subjects were definedas non-responders with a median TG change of 0%. At baseline, responders had higher TG levels in two of four high-density lipoprotein (HDL) subclasses and 909 gene transcripts (p≤0.05) were differentially expressed compared to non-responders. During the intervention, the plasma TG reduction among responders was reflected in TG reductions in fourof six different very low-density lipoprotein subclasses and three of four different HDL subclasses. Compared to non-responders, the expression of 454 transcripts was differentially altered in responders (p≤0.05). Pathway analyses revealed that responders had altered signaling pathways related to development and immune function. In addition,two of the top 10 enriched pathways in responders compared to non-responders were related to lysophosphatidic acid signaling.Conclusion:TG responders and non-responders to omega-3 supplementation have different lipoprotein subclass andPBMC gene expression profiles at baseline and different lipoprotein subclass and PBMC gene expression responses toomega-3 supplementation. These gene expression differences may partially explain the variability in TG response observed after omega-3 supplementation.

• Gjevestad, Gyrd Omholt; Holven, Kirsten Bjørklund; Rundblad, Amanda; Flatberg, Arnar; Myhrstad, Mari & Karlsen, Karina [Show all 10 contributors for this article] (2019). Increased protein intake affects pro-opiomelanocortin (POMC) processing, immune function and IGF signaling in peripheral blood mononuclear cells of home-dwelling old subjects using a genome-wide gene expression approach. Genes & Nutrition. ISSN 1555-8932. 14:32. doi: 10.1186/s12263-019-0654-6. Full text in Research Archive Show summary

  Background: Adequate protein intake among older adults is associated with better health outcomes such as immune function and metabolic regulation of skeletal muscle, but conflicting results make it difficult to define the optimal intake. To further understand the impact of protein intake on metabolic processes, the aim of the study was to explore genome-wide gene expression changes in peripheral blood mononuclear cells (PBMCs) in homedwelling old subjects after increased protein intake for 12weeks. Method: In a parallel double-blind randomized controlled intervention study, subjects (≥ 70years) received a protein-enriched milk (2 × 20g protein/day, n = 14, mean (±SD) age 76.9 ± 4.9years) or an isocaloric carbohydrate drink (n = 17, mean (±SD) age 77.7 ± 4.8years) for breakfast and evening meal for 12weeks. PBMCs were isolated before and after the intervention. Microarray analysis was performed using Illumina technology. Serum levels of gut peptides and insulin growth factor (IGF)-1 were also measured. Results: In total 758 gene transcripts were regulated after increased protein intake, and 649 gene transcripts were regulated after intake of carbohydrates (p < 0.05). Forty-two of these genes were overlapping. After adjusting for multiple testing, 27 of the 758 gene transcripts were regulated (FDR, q-value < 0.25) after protein intake. Of these 25 were upregulated and two downregulated. In particular, genes and signaling pathways involved in proopiomelanocortin (POMC) processing, immune function, and IGF signaling were significantly altered. Conclusions: PBMCs can be used to study gene expression changes after long-term protein intake, as many signaling pathways were regulated after increased protein intake. The functional significance of these findings needs to be further investigated. Trial registration: ClinicalTrials.gov, ID no. NCT02218333. The study was registered on August 18, 2014.

• Larsen, Sunniva Veen; Holven, Kirsten Bjørklund; Ottestad, Inger; Dagsland, Kine Margrethe; Myhrstad, Mari & Ulven, Stine Marie (2018). Plasma fatty acid levels and gene expression related to lipid metabolism in peripheral blood mononuclear cells: A cross-sectional study in healthy subjects. Genes & Nutrition. ISSN 1555-8932. 13(1). doi: 10.1186/s12263-018-0600-z. Full text in Research Archive Show summary

  Background: Solid evidence indicates that intake of marine n-3 fatty acids lower serum triglycerides, and that replacing saturated fatty acids (SFA) with polyunsaturated fatty acids (PUFA) reduces plasma total cholesterol and LDL-cholesterol. The molecular mechanisms underlying these health beneficial effects are however not completely elucidated. The aim of this study was therefore to investigate the expression of genes related to lipid metabolism in peripheral blood mononuclear cells (PBMC) depending on the plasma levels of n-6 and n-3 39 fatty acids and the SFA to PUFA ratio. Methods: Fifty-four healthy subjects were grouped into tertiles (n=18) based on plasma levels of n-6 and n-3 fatty acids and the SFA to PUFA ratio. The PBMC gene expression levels among subjects in the highest versus the lowest tertiles were compared. In total, 285 genes related to cholesterol and triglyceride metabolism were selected for this explorative study. Results: Among the 285 selected genes, 161 were defined as expressed in the PBMCs. The 47 plasma SFA to PUFA ratio was associated with the highest number of significantly different expressed genes (25 gene transcripts), followed by plasma n-6 fatty acid level (15 gene transcripts) and plasma n-3 fatty acid level (8 gene transcripts). In particular, genes involved in cholesterol homeostasis were significantly different expressed among subjects with high compared to low plasma SFA to PUFA ratio. Conclusion: Genes involved in lipid metabolism were differentially expressed in PBMCs depending on the plasma fatty acid levels. This finding may increase our understanding of how fatty acids influence lipid metabolism at a molecular level in humans.

• Henriksen, Christine; Brenno, Silje Golberg; Ulven, Stine Marie; Holven, Kirsten Bjørklund & Ottestad, Inger (2018). Helserelatert livskvalitet og ernæringsstatus blant eldre hjemmeboende over 70 år. Norsk tidsskrift for ernæring (NTFE). ISSN 1503-5034. doi: 10.18261/ntfe.16.2.2. Full text in Research Archive Show summary

  Bakgrunn: Det er vanlig å inkludere helserelatert livskvalitet i kliniske studier, men det er få som har undersøkt dette hos eldre hjemme boende ≥ 70 år. Hensikten med denne studien var primært å beskrive helserelatert livskvalitet blant eldre hjemme boende personer. Sekundært ønsket vi å undersøkeom livskvalitet varierte med kjønn, alder og ernæringsstatus. Materiale og metode: 406 eldre ≥ 70 år deltok i denne tverrsnittstudien. Livskvalitet ble målt ved Short Form (SF)-36 Health Survey versjon 2 som består av åtte domener: fysisk funksjon, fysisk rolle funksjon, smerte, generell helse, sosial funksjon, vitalitet, psykisk rollefunk sjon og mental helse. Ernæringsstatus ble vurdert ved bruk av Mini Nutrition al Assessment (MNA). Resultater: Deltakerne hadde høy helserelatert livskvalitet, men kvinner over 80 år skåret lavere enn de yngre. Gjennomsnittsskår varierte fra 65-91 for kvinner og fra 68-91 hos menn for de ulike domene. Kvinner hadde signifikant lavere poeng sum på tre helsedomener (fysisk funksjon, smerte og psykisk rolle funksjon) sammenliknet med menn. Total MNA poengskår korrelerte signifikant med alle helsedomenene (r=0,13-0,39). Fortolkning: Denne selekterte gruppen av hjemmeboende eldre rapporterte om god helserelatert livskvalitet, men den var lavere blant de over 80 år, spesielt hos kvinner. Kvinner hadde en lavere livskvalitet enn menn. Dårligere ernæringsstatus var assosiert med lavere helserelatert livskvalitet.

• Ottestad, Inger; Ulven, Stine Marie; Øyri, Linn Kristin Lie; Sandvei, Kristin Søfteland; Gjevestad, Gyrd Omholt & Bye, Asta [Show all 10 contributors for this article] (2018). Reduced plasma concentration of branched-chain amino acids in sarcopenic older subjects: a cross-sectional study. British Journal of Nutrition. ISSN 0007-1145. 120(4), p. 445–453. doi: 10.1017/S0007114518001307. Full text in Research Archive Show summary

  Branched chain amino acids (BCAAs) are essential amino acids necessary for muscle mass maintenance. Little is known about the plasma concentrations of BCAAs and the protein intake in relation to sarcopenia. We aimed to compare the non-fasting plasma concentrations of the BCAAs and the dietary protein intake between sarcopenic and nonsarcopenic older adults. Norwegian older home-dwelling adults (≥ 70 years) were invited to a cross-sectional study with no other exclusion criteria than age. Sarcopenic subjects were defined by the diagnostic criteria by the European Working Group on Sarcopenia in Older People. Non- fasting plasma concentrations of eight amino acids were quantified using nuclear magnetic resonance (NMR) spectroscopy. Protein intake was assessed using 2 x 24-h dietary recalls. In this study, 90 out of 417 subjects (22 %) were sarcopenic, and more women (32 %) than men (11 %) were sarcopenic (P < 0.0001). Gender-adjusted non-fasting plasma concentrations of leucine and isoleucine, and the absolute intake of protein (g/d) were significantly lower among the sarcopenic subjects, when compared to nonsarcopenic subjects (P = 0.003, P = 0.026 and P = 0.003, respectively). A similar protein intake was observed in the two groups when adjusted for body weight and gender (1.1 g protein/kg BW/d; P = 0.50). We show that sarcopenia is associated with reduced non-fasting plasma concentration of the BCAAs leucine and isoleucine, and lower absolute intake of protein. More studies are needed to clarify the clinical relevance of these findings, related to maintenance of muscle mass and prevention of sarcopenia.

• Gjevestad, Gyrd Omholt; Ottestad, Inger; Biong, Anne Sofie; Iversen, Per Ole; Retterstøl, Kjetil & Raastad, Truls [Show all 9 contributors for this article] (2017). Consumption of protein-enriched milk has minor effects on inflammation in older adults?A 12-week double-blind randomized controlled trial. Mechanisms of Ageing and Development. ISSN 0047-6374. 162, p. 1–8. doi: 10.1016/j.mad.2017.01.011. Full text in Research Archive Show summary

  Introduction: Aging is associated with increased levels of circulating inflammatory markers and reduced muscle mass and strength. Objective: We investigated whether intake of protein-enriched milk for 12 weeks would influence markers of inflammation among adults ≥70 years of age with reduced physical strength. Methods: In a double-blind randomized controlled intervention study, subjects were randomly allocated into two groups, receiving a protein-enriched milk (2 × 20 g protein/d, n = 14, mean (±SD) age 76.9 ± 4.9 yrs) or an isocaloric carbohydrate drink (n = 17, age 77.7 ± 4.8 yrs) for 12 weeks. We measured serum and mRNA expression levels of inflammatory markers in PBMCs. Results: Significant differences in the mRNA expression of nuclear receptor subfamily, group H, member 3 (NR1H3, encoding the LXRα transcription factor) and interferon gamma (INFG) were observed between groups. The mRNA level of TNFRSF1A was significantly reduced, while the mRNA level of dipeptidyl-peptidase 4 (DPP4) was significantly increased, in the control group. The serum level of TNFα increased significantly in the control group, while sTNFRSF1A increased significantly in both groups, but with no significant differences between groups. Conclusion: Consumption of a low-fat, protein-enriched milk for 12 weeks had minor effects on inflammatory related markers in older adults compared to an isocaloric carbohydrate drink.

• Narverud, Ingunn; Christensen, Jacob J.; Ottestad, Inger; Ulven, Stine Marie & Holven, Kirsten Bjørklund (2017). Misvisende om kosthold i ny nasjonal retningslinje for forebygging av hjerte- og karsykdommer. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 137(20). doi: 10.4045/tidsskr.17.0834. Full text in Research Archive
• Ottestad, Inger; Løvstad, Arne; Gjevestad, Gyrd Omholt; Hamarsland, Håvard; Saltyte-Benth, Jurate & Andersen, Lene Frost [Show all 13 contributors for this article] (2017). Intake of a Protein-Enriched Milk and Effects on Muscle Mass and Strength. A 12-Week Randomized Placebo Controlled Trial among Community-Dwelling Older Adults. The Journal of Nutrition, Health & Aging. ISSN 1279-7707. 21, p. 1160–1169. doi: 10.1007/s12603-016-0856-1. Full text in Research Archive
• Rundblad, Amanda; Holven, Kirsten Bjørklund; Ottestad, Inger; Myhrstad, Mari & Ulven, Stine Marie (2017). High-quality fish oil has a more favourable effect than oxidised fish oil on intermediate-density lipoprotein and LDL subclasses: a randomised controlled trial. British Journal of Nutrition. ISSN 0007-1145. 117(9), p. 1291–1298. doi: 10.1017/S0007114517001167. Full text in Research Archive Show summary

  Fish oil (FO) supplementation reduces the risk of CVD. However, it is not known if FO of different qualities have different effects on lipoprotein subclasses in humans. We aimed at investigating the effects of oxidised FO and high-quality FO supplementation on lipoprotein subclasses and their lipid concentrations in healthy humans. In all, fifty-four subjects completed a double-blind randomised controlled intervention study. The subjects were randomly assigned to receive high-quality FO (n 17), oxidised FO (n 18) or high-oleic sunflower oil capsules (HOSO, n 19) for 7 weeks. The concentration of marine n-3 fatty acids was equal in high-quality FO and oxidised FO (1·6 g EPA+DHA/d). The peroxide value (PV) and anisidine value (AV) were 4 mEq/kg and 3 in high-quality FO and HOSO, whereas the PV and AV in the oxidised FO were 18 mEq/kg and 9. Blood samples were collected at baseline and end of study. NMR spectroscopy was applied for the analysis of lipoprotein subclasses and their lipid concentrations. High-quality FO reduced the concentration of intermediate-density lipoprotein (IDL) particles and large, medium and small LDL particles, as well as the concentrations of total lipids, phospholipids, total cholesterol, cholesteryl esters and free cholesterol in IDL and LDL subclasses compared with oxidised FO and HOSO. Hence, high-quality FO and oxidised FO differently affect lipid composition in lipoprotein subclasses, with a more favourable effect mediated by high-quality FO. In future trials, reporting the oxidation levels of FO would be useful.

• Gjevestad, Gyrd Omholt; Hamarsland, Håvard; Raastad, Truls; Ottestad, Inger; Christensen, Jacob J. & Eckardt, Kristin [Show all 10 contributors for this article] (2017). Gene expression is differentially regulated in skeletal muscle and circulating immune cells in response to an acute bout of high-load strength exercise. Genes & Nutrition. ISSN 1555-8932. 12:8, p. 1–11. doi: 10.1186/s12263-017-0556-4. Full text in Research Archive Show summary

  Background: High-intensity exercise induces many metabolic responses. In is unknown whether the response in the peripheral blood mononuclear cells (PBMCs) reflects the response in skeletal muscle and whether mRNA expression after exercise can be modulated by nutritional intake. The aims were to (i) investigate the effect of dairy proteins on acute responses to exercise in skeletal muscle and PBMCs measuring gene expression and (ii) compare this response in young and older subjects. Methods: We performed two separate studies in young (20–40 years) and older subjects (≥70 years). Subjects were randomly allocated to a milk group or a whey group. Supplements were provided immediately after a standardized exercise session. We measured mRNA expression of selected genes after a standardized breakfast and 60/120 min after finishing the exercise, using RT-qPCR. Results: We observed no significant differences in mRNA expression between the milk and the whey group; thus, we merged both groups for further analysis. The mRNA expression of IL6, TNF, and CCL2 in skeletal muscle increased significantly after exercise compared with smaller or no increase, in mRNA expression in PBMCs in all participants. The mRNA expression of IL1RN, IL8, and IL10 increased significantly in skeletal muscle and PBMCs. Some mRNA transcripts were differently regulated in older compared to younger participants in PBMCs. Conclusions: An acute bout of heavy-load strength exercise, followed by protein supplementation, caused overlapping, but also unique, responses in skeletal muscle and PBMCs, suggesting tissue-specific functions in response to exercise. However, no different effects of the different protein supplements were observed. Altered mRNA expressions in PBMCs of older participants may affect regenerative mechanisms.

• Ulven, Stine Marie; Leder, Lena; Elind, Elisabeth; Ottestad, Inger; Christensen, Jacob J. & Telle-Hansen, Vibeke [Show all 17 contributors for this article] (2016). Exchanging a few commercial, regularly consumed food items with improved fat quality reduces total cholesterol and LDL-cholesterol: A double-blind, randomised controlled trial. British Journal of Nutrition. ISSN 0007-1145. 116(8), p. 1383–1393. doi: 10.1017/S0007114516003445. Full text in Research Archive Show summary

  The healthy Nordic diet has been previously shown to have health bene fi cial effects among subjects at risk of CVD. However, the extent of food changes needed to achieve these effects is less explored. The aim of the present study was to investigate the effects of exchanging a few commercially available, regularly consumed key food items (e.g. spread on bread, fat for cooking, cheese, bread and cereals) with improved fat quality on total cholesterol, LDL-cholesterol and in fl ammatory markers in a double-blind randomised, controlled trial. In total, 115 moderately hypercholesterolaemic, non-statin-treated adults (25 – 70 years) were randomly assigned to an experimental diet group (Ex-diet group) or control diet group (C-diet group) for 8 weeks with commercially available food items with different fatty acid composition (replacing SFA with mostly n -6 PUFA). In the Ex-diet group, serum total cholesterol ( P < 0 · 001) and LDL-cholesterol ( P < 0 · 001) were reduced after 8 weeks, compared with the C-diet group. The difference in change between the two groups at the end of the study was − 9 and − 11 % in total cholesterol and LDL-cholesterol, respectively. No difference in change in plasma levels of in fl ammatory markers (high-sensitive C-reactive protein, IL-6, soluble TNF receptor 1 and interferon- γ ) was observed between the groups. In conclusion, exchanging a few regularly consumed food items with improved fat quality reduces total cholesterol, with no negative effect on levels of inflammatory markers. This shows that an exchange of a few commercially available food items was easy and manageable and led to clinically relevant cholesterol reduction, potentially affecting future CVD risk.

• Torvik, Kristin; Narverud, Ingunn; Ottestad, Inger; Svilaas, Arne B; Gran, Jon Michael & Retterstøl, Kjetil [Show all 11 contributors for this article] (2016). Dietary counseling is associated with an improved lipid profile in children with familial hypercholesterolemia. Atherosclerosis. ISSN 0021-9150. 252, p. 21–27. doi: 10.1016/j.atherosclerosis.2016.07.913. Full text in Research Archive
• Myhrstad, Mari; Ottestad, Inger; Günther, Clara-Cecilie; Ryeng, Einar; Holden, Marit & Nilsson, Astrid [Show all 11 contributors for this article] (2016). The PBMC transcriptome profile after intake of oxidized versus high-quality fish oil: an explorative study in healthy subjects. Genes & Nutrition. ISSN 1555-8932. 11:16. doi: 10.1186/s12263-016-0530-6. Full text in Research Archive Show summary

  Background: Marine long-chain polyunsaturated fatty acids are susceptible to oxidation, generating a range of different oxidation products with suggested negative health effects. The aim of the present study was to utilize sensitive high-throughput transcriptome analyses to investigate potential unfavorable effects of oxidized fish oil (PV: 18 meq/kg; AV: 9) compared to high-quality fish oil (PV: 4 meq/kg; AV: 3). Methods: In a double-blinded randomized controlled study for seven weeks, 35 healthy subjects were assigned to 8 g of either oxidized fish oil or high quality fish oil. The daily dose of EPA+DHA was 1.6 g. Peripheral blood mononuclear cells were isolated at baseline and after 7 weeks and transcriptome analyses were performed with the illuminaHT-12 v4 Expression BeadChip. Results: No gene transcripts, biological processes, pathway or network were significantly changed in the oxidized fish oil group compared to the fish oil group. Furthermore, gene sets related to oxidative stress and cardiovascular disease were not differently regulated between the groups. Within group analyses revealed a more prominent effect after intake of high quality fish oil as 11 gene transcripts were significantly (FDR < 0.1) changed from baseline versus three within the oxidized fish oil group. Conclusion: The suggested concern linking lipid oxidation products to short-term unfavorable health effects may therefore not be evident at a molecular level in this explorative study. Trial registration: ClinicalTrials.gov, NCT01034423

• Ottestad, Inger; Løvstad, Amund T.; Gjevestad, Gyrd Omholt; Hamarsland, Håvard; Benth, Jurate Saltyte & Andersen, Lene Frost [Show all 13 contributors for this article] (2016). Intake of a protein-enriched milk and effects on muscle mass and strength. A 12-week randomized placebo controlled trial among community-dwelling older adults. The Journal of Nutrition, Health & Aging. ISSN 1279-7707. 21, p. 1160–1169. doi: 10.1007/s12603-016-0856-1. Full text in Research Archive
• Ottestad, Inger; Nordvi, Berit; Vogt, Kjell Gjermund; Holck, Marianne; Halvorsen, Bente & Brønner, Kirsti Wettre [Show all 10 contributors for this article] (2016). Bioavailability of n-3 fatty acids from n-3 enriched foods and fish oil with different oxidative quality in healthy humans – a randomized single meal cross-over study. Journal of Nutritional Science (JNS). 5(e43), p. 1–8. doi: 10.1017/jns.2016.34. Full text in Research Archive Show summary

  Regular consumption of long-chain n-3 fatty acids (LC n-3 FA) reduces postprandial triacylglycerolaemia. Functional foods and supplements are alternative sources of LC n-3 FA; however, emulsification technologies, food matrices and altered lipid oxidation levels affect their bioavailability. Moreover, which functional foods are optimal LC n-3 FA carriers is unknown. The aim of the study was to determine the bioavailability of LC n-3 FA and the postprandial TAG response after the intake of oxidised or non-oxidised cod liver oil and after the intake of emulsified or non-emulsified LC n-3 FA using novel functional food items as LC n-3 FA carriers in a randomised cross-over acute study. A total of twenty-four healthy subjects completed the study in which subjects consumed one of four different test meals containing 1·5 g LC n-3 FA, or a control meal with no LC n-3 FA. Postprandial TAG-rich lipoproteins were isolated and their fatty acid composition was measured. The LC n-3 FA from emulsified foods were more rapidly incorporated into TAG-rich lipoproteins compared with non-emulsified foods. The incorporation of LC n-3 FA was similar for oils emulsified in yogurt or juice and was unaffected by the oxidative status of the oil. Postprandial TAG levels did not differ among the various test meals. In conclusion, emulsification increases the bioavailability of LC n-3 FA through a more rapid incorporation into TAG-rich lipoproteins, and juice and yogurt are equally suited as LC n-3 FA carriers. The acute intake of oxidised cod liver oil does not influence the incorporation of LC n-3 FA into TAG-rich lipoproteins.

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• Erichsen, Marianne; Ottestad, Inger; Solheim, Tora S; Paur, Ingvild; Thronæs, Morten & Follestad, Turid [Show all 14 contributors for this article] (2025). Beyond Starvation: Exploring hypermetabolism in incurable cancer. Full text in Research Archive
• Balstad, Trude Rakel; Bråtveit, Marianne; Solheim, Tora S; Koteng, Lisa Heide; Bye, Asta & Jakobsen, Rasmus Dahl [Show all 12 contributors for this article] (2024). Validity of dietary intake methods in cancer cachexia. Full text in Research Archive
• Koteng, Lisa Heide; Sand, Kari; Paur, Ingvild; Bye, Asta; Ervik, Bente & Solheim, Tora S [Show all 8 contributors for this article] (2024). Why Norwegian oncologists do not use diagnosis codes for malnutrition. Full text in Research Archive
• Balstad, Trude Rakel; Solheim, Tora Skeidsvoll; Ottestad, Inger; Paur, Ingvild; Sande, Rikka Frøyen & Markhus, Emilie Hjønnevåg [Show all 16 contributors for this article] (2024). Parenteral nutrition in advanced cancer: Exploring the clinical landscape. Full text in Research Archive
• Koteng, Lisa Heide; Sand, Kari; Paur, Ingvild; Bye, Asta; Ervik, Bente & Solheim, Tora Skeidsvoll [Show all 8 contributors for this article] (2024). Exploring the barriers to diagnosing malnutrition in cancer patients: A study on oncologists' perspectives. Full text in Research Archive
• Øhman, Elisabeth Adolfsen; Fossli, Maria; Ottestad, Inger Olaug; Holven, Kirsten Bjørklund; Ulven, Stine Marie & Løland, Beate Fossum [Show all 7 contributors for this article] (2024). Dietary treatment postpartum in women with obesity reduces weight and prevents weight gain: a randomised controlled trial. Full text in Research Archive
• Erichsen, Marianne; Balstad, Trude Rakel; Paur, Ingvild; Hansson, Patrik; Paulsen, Ørnulf & Løhre, Erik Torbjørn [Show all 17 contributors for this article] (2024). Parenteral Nutrition in Advanced Cancer: Exploring the clinical landscape. Full text in Research Archive
• Øhman, Elisabeth Adolfsen; Fossli, Maria; Ottestad, Inger; Holven, Kirsten Bjørklund; Ulven, Stine Marie & Løland, Beate Fossum [Show all 7 contributors for this article] (2023). Effect of a postpartum weight loss intervention in women with obesity: a randomized controlled trial. Full text in Research Archive
• Øhman, Elisabeth Adolfsen; Fossli, Maria; Ottestad, Inger; Holven, Kirsten Bjørklund; Ulven, Stine Marie & Løland, Beate Fossum [Show all 7 contributors for this article] (2023). Kostprogram postpartum reduserer vekt og forebygger vektoppgang blant kvinner med fedme – en randomisert kontrollert studie. 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
• Ulven, Stine Marie; Ottestad, Inger Olaug; Christensen, Jacob Juel & Holven, Kirsten Bjørklund (2023). Inflammatory markers and frailty in home-dwelling elderly, a cross-sectional study. Full text in Research Archive
• Øhman, Elisabeth Adolfsen; Fossli, Maria; Ottestad, Inger; Holven, Kirsten Bjørklund; Ulven, Stine Marie & Løland, Beate Fossum [Show all 7 contributors for this article] (2023). Effect of a postpartum weight loss intervention in women with obesity: a randomized controlled trial. Full text in Research Archive
• Holven, Kirsten Bjørklund; Ulven, Stine Marie; Ottestad, Inger Olaug & Christensen, Jacob Juel (2023). Inflammatory markers and frailty markers in home-dwelling elderly, a cross-sectional study. Full text in Research Archive
• Holven, Kirsten Bjørklund; Ulven, Stine Marie; Christensen, Jacob Juel & Ottestad, Inger Olaug (2023). Betydning av kosten for endring i skrøpelighet hos hjemmeboende eldre etter 8 års oppfølging. Full text in Research Archive
• Ottestad, Inger; Ræder, Hanna; Soteland, Esther B. B.; Toleikyte-Celestino, Ieva; Høidalen, Anne & Warmbrodt, Nicole (2022). Nutritional impact symptoms and weight loss after esophageal and gastric cancer surgery. Full text in Research Archive
• Ottestad, Inger; Thoresen, Lene; Tangvik, Randi Julie; Fjeldstad, Siv Hilde; Authen, Mina Marie & Følstad, Sandra [Show all 14 contributors for this article] (2022). Quality of Nutritional Treatment in Norwegian Hospitals. Full text in Research Archive
• Øhman, Elisabeth Adolfsen; Fossli, Maria; Brekke, Hilde Kristin; Holven, Kirsten Bjørklund; Ulven, Stine Marie & Ottestad, Inger [Show all 7 contributors for this article] (2022). Dietary treatment prevents postpartum weight gain in women with obesity: a randomised controlled trial. Full text in Research Archive Show summary

  Background: Women with pre-pregnancy obesity have an increased risk of retaining or gaining weight postpartum. Previously, we performed a dietary treatment which resulted in sustained weight loss and improved cardiometabolic risk factors in lactating women with a mean BMI=30 kg/m2. However, evidence is lacking for higher BMI classes. The aim of this study was to examine the effects of the dietary treatment on change in weight and markers of lipid- and glucose metabolism as well as postpartum weight retention (PPWR) and change in waist-and-hip-circumference in postpartum women with obesity. Methodology: At baseline, approximately 8 weeks postpartum, 29 women were randomised to a 12-week dietary treatment for weight loss (n=14) or to a control treatment (n=15) receiving a brochure on healthy eating. Measurements were made at baseline and 3 and 12 months later. Data was analysed using mixed model. Results: Mean BMI at baseline was 40.0 ± 5.2 kg/m2. Weight change after 3 months was -2.3 ± 3.1 kg in the diet group compared to 1.7 ± 3.1 kg in the control group (P=0.025), and -4.2 ± 5.6 kg in the diet group compared to 4.8 ± 11.8 kg in the control group after 12 months (P=0.010). The dietary treatment led to reduced waist circumference (P<0.032) and PPWR (P<0.002) compared to the control treatment at both time points. There were no effects of the treatment on markers of lipid- and glucose metabolism. Conclusion: The dietary treatment prevented postpartum women with obesity from retaining or gaining weight, and may even reduce weight.

• Rundblad, Amanda; Larsen, Sunniva Veen; Myhrstad, Mari; Ottestad, Inger; Thoresen, Magne & Holven, Kirsten Bjørklund [Show all 7 contributors for this article] (2019). Characterization of PBMC gene expression and lipoprotein subclasses among plasma TG responders and non-responders. Full text in Research Archive
• Holven, Kirsten Bjørklund; Sæther, Thomas; Hjorth, Marit; Dalen, Knut Tomas; Ulven, Stine Marie & Ottestad, Inger [Show all 7 contributors for this article] (2019). Kan fisk utnyttes enda mer og samtidig fremme folkehelsen? Norsk tidsskrift for ernæring (NTFE). ISSN 1503-5034. 17(2), p. 20–22. Full text in Research Archive
• Sande, Rikka Frøyen; Thoresen, Lene; Løhre, Erik Torbjørn; Nygard, Astrid Signe; Paulsen, Ørnulf & Ottestad, Inger [Show all 8 contributors for this article] (2019). Parenteral nutrition therapy in patients with incurable cancer: A retrospective medical chart review of current practice. Full text in Research Archive Show summary

  Rationale: Indication for use, dose and duration of parenteral nutrition (PN) in patients with incurable cancer is understudied. The aim of the study was to describe current practice of PN treatment in adult patients with incurable cancer at St. Olavs University Hospital, Trondheim, Norway. Methods: A retrospective medical chart review of patients with incurable cancer receiving PN between 2011 and 2017 was conducted. Of 271 identified patients, data from the first 78 patients was included in this preliminary analysis. Medical information was collected from start of PN until patients’ death. Results: The mean (SD) age was 63.5 (12.9) years, 41 women and 37 men. All patients received PN concomitant with anti-cancer treatment at some point in time. The most common indications for PN were “insufficient oral or enteral intake” (n=67) or “gastrointestinal malfunction” (n=17). At start of PN, there were no differences between subgroups in s-albumin, C-reactive protein level, metastatic disease, or ascites. The main reason for discontinuation of PN was imminently dying patient (n=36), patient preferences (n=19), and complications (n=12). The table presents available data on PN treatment and survival in subgroups defined by duration of PN treatment. Data presented as n or median (Q1-Q3). Variables < 2 weeks 2 weeks -1 month 1 month - 2 months > 2 months P1 n Patients (n) 14 20 16 16 66 PN treatment Highest received PN dose, kcal 1100 (612-1600)#,¤ 1600 (1100-2200)# 1600 (1100-1600) 1750 (1450-2200)¤ 0.001 62 Received dose (percentage of estimated energy need) 73 (43-73) 78 (62-101) 69 (50-94) 97 (73-118) 0.03 52 Documented oral food intake, n 9 16 15 15 0.09 55 Survival From start of PN, days 19 (13-74)& 39 (26- 384) 61 (43-115) 168 (88-295)& 0.001 66 From PN termination, days 10 (4-70) 16 (5-358)§ 4.5 (1-70) 2 (1-7)§ 0.016 66 1Kruskal-Wallis test, Dunn’s Post Hoc test; # P=0.04, ¤ p=0.003, & P=0.001, § P=0.02 Conclusion: To our knowledge, this is the first study describing clinical practice with respect to dose, duration and termination of PN in incurable cancer patients. Preliminary data suggest that the use of PN was dynamic and differentiated. Termination of PN was based on expected patient survival, patient preferences, and treatment complications.

• Kardel, Kristin Reimers; Hägg, Sara B.; Gjevre, Ragnhild; Sævre, Synne Risan; Henriksen, Tore & Roland, Marie Cecilie [Show all 7 contributors for this article] (2019). Helseutfall hos gravide kvinner med overvekt og barnet ved fødsel. Full text in Research Archive
• Hustad, Kristin Solheim; Rundblad, Amanda; Ottestad, Inger; Christensen, Jacob J.; Holven, Kirsten Bjørklund & Ulven, Stine Marie (2019). Intake of fatty fish and lipoprotein subclass profiling in healthy adults: a cross-sectional analysis. Full text in Research Archive
• Hustad, Kristin Solheim; Rundblad, Amanda; Ottestad, Inger; Christensen, Jacob J.; Holven, Kirsten Bjørklund & Ulven, Stine Marie (2019). Intake of fatty fish and lipoprotein subclass profiling in healthy adults: a cross-sectional analysis. Full text in Research Archive
• Ottestad, Inger; Ulven, Stine Marie; Sandvei, Kristin Søfteland; Carlsen, Monica Hauger; Gundersen, Thomas & Gjevestad, Gyrd Omholt [Show all 8 contributors for this article] (2019). Iodine status and effect of increased intake of milk among older Norwegian adults. Full text in Research Archive
• Larsen, Sunniva Veen; Holven, Kirsten Bjørklund; Ottestad, Inger; Dagsland, Kine Næss; Myhrstad, Mari & Ulven, Stine Marie (2018). Correction: Plasma fatty acid levels and gene expression related to lipid metabolism in peripheral blood mononuclear cells: A cross-sectional study in healthy subjects [Genes Nutr., 13, (2018) (9)] DOI: 10.1186/s12263-018-0600-z. Genes & Nutrition. ISSN 1555-8932. 13(1). doi: 10.1186/s12263-018-0604-8. Full text in Research Archive
• Larsen, Sunniva Veen; Holven, Kirsten Bjørklund; Ottestad, Inger; Dagsland, Kine Margrethe; Myhrstad, Mari & Ulven, Stine Marie (2018). Plasma fatty acid levels and gene expression related to lipid metabolism in peripheral blood mononuclear cells: a cross-sectional study in healthy subjects. Full text in Research Archive
• Larsen, Sunniva Veen; Holven, Kirsten Bjørklund; Ottestad, Inger; Dagsland, Kine Margrethe; Myhrstad, Mari & Ulven, Stine Marie (2018). Plasma fatty acid levels and gene expression related to lipid metabolism in peripheral blood mononuclear cells: a cross-sectional study in healthy subjects. Full text in Research Archive
• Larsen, Sunniva Veen; Holven, Kirsten Bjørklund; Ottestad, Inger; Dagsland, Kine Margrethe; Myhrstad, Mari & Ulven, Stine Marie (2018). Plasma fatty acid levels and gene expression related to lipid metabolism in peripheral blood mononuclear cells: a cross-sectional study in healthy subjects. Full text in Research Archive
• Ulven, Stine Marie; Christensen, Jacob J.; Nygård, Ottar; Svardal, Asbjørn M.; Leder, Lena & Ottestad, Inger [Show all 12 contributors for this article] (2018). Using metabolic profiling to explore molecular effects of replacing saturated fat with polyunsaturated fat- a randomized controlled dietary intervention study. Full text in Research Archive
• Ulven, Stine Marie; Christensen, Jacob J.; Nygård, Ottar; Svardal, Asbjørn M.; Leder, Lena & Ottestad, Inger [Show all 12 contributors for this article] (2018). Using metabolic profiling to explore molecular effects of replacing saturated fat with polyunsaturated fat- a randomized controlled dietary intervention study. Full text in Research Archive
• Ulven, Stine Marie; Christensen, Jacob J.; nygaard, ottar; Svardal, Asbjørn M.; Leder, Lena & Ottestad, Inger [Show all 8 contributors for this article] (2018). Using metabolic profiling and gene expression analyses to explore molecular effects of replacing saturated fat with polyunsaturated fat- a randomized controlled dietary intervention study. Full text in Research Archive
• Rundblad, Amanda; Larsen, Sunniva Veen; Myhrstad, Mari; Ottestad, Inger; Thoresen, Magne & Holven, Kirsten Bjørklund [Show all 7 contributors for this article] (2018). Gene expression changes in plasma triglyceride responders and non-responders to omega-3 supplementation. Full text in Research Archive
• Rundblad, Amanda; Holven, Kirsten Bjørklund; Ottestad, Inger; Myhrstad, Mari & Ulven, Stine Marie (2018). High-quality fish oil has a more favourable effect than oxidised fish oil on intermediate density lipoprotein and LDL subclasses: a randomised controlled trial. Full text in Research Archive
• Narverud, Ingunn; Christensen, Jacob J. & Ottestad, Inger (2017). Klin kokos fra Berit Nordstrand. Facebook. Full text in Research Archive
• Larsen, Sunniva Veen; Holven, Kirsten Bjørklund; Ottestad, Inger; Dagsland, Kine Næss; Myhrstad, Mari & Ulven, Stine Marie (2017). Plasma fatty acid levels and gene expression related to lipid metabolism in peripheral blood mononuclear cells: a cross-sectional study in healthy subjects. Full text in Research Archive
• Rundblad, Amanda; Holven, Kirsten Bjørklund; Ottestad, Inger; Myhrstad, Mari & Ulven, Stine Marie (2017). High-quality fish oil has a more favourable effect than oxidised fish oil on intermediate density lipoprotein and LDL subclasses. Full text in Research Archive
• Rundblad, Amanda; Holven, Kirsten Bjørklund; Ottestad, Inger; Myhrstad, Mari & Ulven, Stine Marie (2017). High-quality fish oil has a more favourable effect than oxidized fish oil on intermediate-density lipoprotein and LDL subclasses: a randomised controlled trial. Full text in Research Archive
• Rundblad, Amanda; Holven, Kirsten Bjørklund; Ottestad, Inger; Myhrstad, Mari & Ulven, Stine Marie (2017). High quality fish oil has a more favourable effect than oxidized fish oil on intermediate and low density lipoprotein subclasses. Full text in Research Archive
• Brynildsen, Åslaug; Narverud, Ingunn; Christensen, Jacob J. & Ottestad, Inger (2017). Så enkelt får barnet ditt rett type fett. Full text in Research Archive
• Ottestad, Inger; Narverud, Ingunn; Christensen, Jacob J.; Rundblad, Amanda; Øyri, Linn Kristin Lie & Larsen, Sunniva Veen [Show all 11 contributors for this article] (2017). Ost - venn eller fiende for hjertehelsa? Full text in Research Archive
• Brynildsen, Åslaug; Narverud, Ingunn; Christensen, Jacob J. & Ottestad, Inger (2017). Så enkelt får barnet ditt rett type fett. http://www.uio.no/. Full text in Research Archive
• Rundblad, Amanda; Holven, Kirsten Bjørklund; Ottestad, Inger; Myhrstad, Mari & Ulven, Stine Marie (2017). High quality fish oil has a more favourable effect than oxidized fish oil on intermediate and low density lipoprotein subclasses. Full text in Research Archive
• Brynildsen, Åslaug; Narverud, Ingunn; Christensen, Jacob J. & Ottestad, Inger (2017). Så enkelt får barnet ditt rett type fett. www.forskning.no. Full text in Research Archive
• Rundblad, Amanda; Holven, Kirsten Bjørklund; Ottestad, Inger; Myhrstad, Mari & Ulven, Stine Marie (2017). Quality of fish oil has an impact on lipid composition in intermediate and low density lipoprotein subclasses. Full text in Research Archive
• Ottestad, Inger (2017). Har økt inntak av protein en gunstig effekt på muskelmasse og muskelstyrke hos eldre hjemmeboende over70 år? Full text in Research Archive
• Ottestad, Inger & Gjevestad, Gyrd Omholt (2017). Eldre anbefales mer protein – har mer protein betydning for sarkopeni? Full text in Research Archive
• Ulven, Stine Marie; Holven, Kirsten Bjørklund; Christensen, Jacob J.; Leder, Lena & Ottestad, Inger (2017). Use of metabolomics in the NOMA study. Full text in Research Archive
• Ulven, Stine Marie; Christensen, Jacob J.; Leder, Lena; Ottestad, Inger & Holven, Kirsten Bjørklund (2017). Using metabolic profiling to explore mechanisms that cause LDL cholesterol to decrease following replacement of saturated fat with polyunsaturated fat– a randomized controlled dietary intervention study. Full text in Research Archive
• Rognø, Linn merete; Ottestad, Inger; Christensen, Jacob J. & Narverud, Ingunn (2017). Mye fett i kostholdet er sunt. [Journal]. klikk.no. Full text in Research Archive
• Hägg, Sara B.; Gjevre, Ragnhild; Kardel, Kristin Reimers; Roland, Marie Cecilie; Henriksen, Tore & Ottestad, Inger (2017). Obesity and pregnancy: Are changes in weight, blood lipids and glucose levels during pregnancy associated with health status of mother and child? Full text in Research Archive
• Ottestad, Inger; Løvstad, Amund; Gjevestad, Gyrd Omholt; Hamarsland, Håvard; Benth, Jurate Saltyte & Andersen, Lene Frost [Show all 13 contributors for this article] (2016). Intake of a protein-enriched milk and effects on muscle mass and strength. A 12-week randomized placebo controlled trial among community-dwelling older adults. Full text in Research Archive
• Kolbjørnsen, Lisa & Ottestad, Inger (2016). Effekter av helfete meieriprodukter på LDL-kolesterol: En oppsummering av nyere randomiserte kontrollerte studier. Norsk tidsskrift for ernæring (NTFE). ISSN 1503-5034. Full text in Research Archive
• Gjevestad, Gyrd Omholt; Ottestad, Inger; Biong, Anne Sofie; Iversen, Per Ole; Retterstøl, Kjetil & Raastad, Truls [Show all 9 contributors for this article] (2016). Consumption of protein-enriched milk does not affect inflammation in elderly subjects - a 12 week double-blind randomized controlled trial. Full text in Research Archive
• Ottestad, Inger; Christensen, Jacob J. & Narverud, Ingunn (2016). Forskere villeder om mettet fett. Full text in Research Archive
• Hamrin, Margaretha; Christensen, Jacob J.; Ottestad, Inger; Narverud, Ingunn; Gjevestad, Gyrd Omholt & Rundblad, Amanda [Show all 13 contributors for this article] (2016). Fra Beverly Hills-dietten til Nordisk kost – hva virker? FH-magasinet. Full text in Research Archive
• Ulven, Stine Marie; Leder, Lena; Elind, Elisabeth; Ottestad, Inger; Christensen, Jacob Juel & Telle-Hansen, Vibeke [Show all 10 contributors for this article] (2015). EXCHANGING KEY FOOD ITEMS IN DAILY DIET IMPROVES FAT QUALITY AND REDUCES TOTAL CHOLESTEROL AND LDL CHOLESTEROL– A RANDOMIZED CONTROLLED TRIAL. Full text in Research Archive
• Ulven, Stine Marie; Leder, Lena; Elind, Elisabeth; Ottestad, Inger; Christensen, Jacob Juel & Telle-Hansen, Vibeke [Show all 16 contributors for this article] (2015). REPLACING DIETARY SATURATED FAT WITH POLYUNSATURATED FAT REDUCES TOTAL CHOLESTEROL AND LDL CHOLESTEROL IN HEALTHY SUBJECTS WITH MODERATE HYPERCHOLESTEROLAEMIA – A RANDOMIZED CONTROLLED TRIAL. Full text in Research Archive

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