Nasser Ezzatkhah Bastani

• Olsen, Thomas; Elshorbagy, Amany; Tore, Elena C.; Bastani, Nasser Ezzatkhah; Stolt, Emma Theresia Kjelland & Blokland, Gabriëlla A.M. [Show all 16 contributors for this article] (2026). Higher plasma serine levels are associated with favorable values of metabolic health markers among middle-aged and older adults in The Maastricht Study. GeroScience. ISSN 2509-2715. doi: 10.1007/s11357-026-02237-4. Full text in Research Archive Show summary

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

• Stålberg, Stina Margrethe; Silwal-Pandit, Laxmi; Bastani, Nasser Ezzatkhah; Nebdal, Daniel J.H.; Lingjærde, Ole Christian & Skålhegg, Bjørn Steen [Show all 7 contributors for this article] (2024). Preoperative profiles of plasma amino acids and derivatives distinguish periampullary cancer and benign disease. BMC Cancer. 24(1). doi: 10.1186/s12885-024-12320-8. Full text in Research Archive Show summary

  Periampullary cancers, including pancreatic ductal adenocarcinoma, ampullary-, cholangio-, and duodenal carcinoma, are frequently diagnosed in an advanced stage and are associated with poor overall survival. They are difficult to differentiate from each other and challenging to distinguish from benign periampullary disease preoperatively. To improve the preoperative diagnostics of periampullary neoplasms, clinical or biological markers are warranted. In this study, 28 blood plasma amino acids and derivatives from preoperative patients with benign (N = 45) and malignant (N = 72) periampullary disease were analyzed by LC-MS/MS. Principal component analysis and consensus clustering both separated the patients with cancer and the patients with benign disease. Glutamic acid had significantly higher plasma expression and 15 other metabolites significantly lower plasma expression in patients with malignant disease compared with patients having benign disease. Phenylalanine was the only metabolite associated with improved overall survival (HR = 0.50, CI 0.30–0.83, P < 0.01). Taken together, plasma metabolite profiles from patients with malignant and benign periampullary disease were significantly different and have the potential to distinguish malignant from benign disease preoperatively.

• Nilsen, Lotte LK; Lambert, Max Norman Tandrup; Haubek, Dorte; Bastani, Nasser Ezzatkhah; Skålhegg, Bjørn Steen & Overgaard, Kristian [Show all 8 contributors for this article] (2024). The Effect of Alginate Encapsulated Plant-Based Carbohydrate and Protein Supplementation on Recovery and Subsequent Performance in Athletes. Nutrients. 16(3). doi: 10.3390/nu16030413. Full text in Research Archive Show summary

  The main purpose of this study was to investigate the effect of a novel alginate-encapsulated carbohydrate–protein (CHO–PRO ratio 2:1) supplement (ALG) on cycling performance. The ALG, designed to control the release of nutrients, was compared to an isocaloric carbohydrate-only control (CON). Alginate encapsulation of CHOs has the potential to reduce the risk of carious lesions. Methods: In a randomised cross-over clinical trial, 14 men completed a preliminary test over 2 experimental days separated by ~6 days. An experimental day consisted of an exercise bout (EX1) of cycling until exhaustion at W~73%, followed by 5 h of recovery and a subsequent time-to-exhaustion (TTE) performance test at W~65%. Subjects ingested either ALG (0.8 g CHO/kg/hr + 0.4 g PRO/kg/hr) or CON (1.2 g CHO/kg/hr) during the first 2 h of recovery. Results: Participants cycled on average 75.2 ± 5.9 min during EX1. Levels of plasma branched-chain amino acids decreased significantly after EX1, and increased significantly with the intake of ALG during the recovery period. During recovery, a significantly higher plasma insulin and glucose response was observed after intake of CON compared to ALG. Intake of ALG increased plasma glucagon, free fatty acids, and glycerol significantly. No differences were found in the TTE between the supplements (p = 0.13) nor in the pH of the subjects’ saliva. Conclusions: During the ALG supplement, plasma amino acids remained elevated during the recovery. Despite the 1/3 less CHO intake with ALG compared to CON, the TTE performance was similar after intake of either supplement.

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

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

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

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

• Turner, Cheryl; Refsum, Helga & Bastani, Nasser Ezzatkhah (2023). Determination of underivatized amino acids in human plasma using ion pair liquid chromatography/tandem mass spectrometry. Journal of chromatography. B. ISSN 1570-0232. 1229, p. 1–9. doi: 10.1016/j.jchromb.2023.123893. Full text in Research Archive Show summary

  Accurate quantification of amino acids (AA) is essential for several applications, including clinical research, food analysis, and pharmaceutical studies. In this study, we developed an analytical method based on liquid chromatography with electrospray ionization coupled to tandem mass spectrometry detection (LC-ESI-MS/MS). This method was devised to accurately quantify a spectrum of amino acids, notably taurine, creatinine, glutathione (GSH), and sulfur-containing amino acids (SAAs) such as methionine, cysteine, and homocysteine, using only 10 μL of human plasma. A stable isotope derivative of each AA is used as an internal standard (IS) for accurate quantification. For retention and separation on a C18 column, heptafluorobutyric acid (HFBA) was employed as an ion pair agent. Multiple reaction monitoring (MRM) in positive mode with the precursor-to-product ion transitions at m/z is used for quantification. The method showed excellent linearity for all AA with a high correlation coefficient (r > 0.9927). The linear fit indicates that the detector response is linear over the tested range of standard concentrations. The accuracy and precision of the method were within the acceptable range of 92–110% and < 15%, respectively. The limit of detection (LOD) and limit of quantification (LOQ) were in the range of 0.001–1.80 µM and 0.004–6.0 µM, respectively. No significant ion suppression or carry over was observed. In conclusion, the assay was validated and found to have adequate accuracy, precision, linearity, sensitivity and selectivity. The assay has been successfully applied to the analysis of human plasma.

• Wouda, Matthijs Ferdinand; Slettahjell, Hanne Bjørg; Lundgaard, Eivind; Bastani, Nasser Ezzatkhah; Raastad, Truls & Blomhoff, Rune [Show all 7 contributors for this article] (2023). Acute changes in antioxidants and oxidative stress to vigorous arm exercise: an intervention trial in persons with spinal cord injury and healthy controls. Spinal Cord Series and Cases. 9. doi: 10.1038/s41394-023-00590-6. Full text in Research Archive Show summary

  Background: Literature remains unclear on possible health benefits and risks assosciated with high intensity exercise for persons with SCI. Elevated oxidative stress levels might influence their ability to exercise at high intensity. We investigated several biomarkers of oxidative stress and antioxidant defense at rest, during and after vigorous exercise among persons with chronic SCI. Setting: Sunnaas Rehabilitation Hospital, Norway. Methods: Six participants (five males) with chronic SCI (AIS A, injury level thoracic 2–8, >1 year postinjury) and six matched able-bodied controls performed two maximal arm-cranking tests, with one-three days in between. During the second exercise test, participants performed three bouts with four minutes arm cranking at high intensity (85–95% of peak heart rate (HRpeak)), before they reached maximal effort. Blood and urine biomarkers for oxidative stress and antioxidant levels were collected at six time points at the day of the second exercise test; baseline, at high intensity exercise, at maximal effort, at five, 30 and 60 min post-exercise, and 24 h post exercise. Results: Participants with SCI had significant lower levels of creatinine (∆16 µmol/L, p = 0.03), α-carotene (∆0.14 nmol/L, p ＜ 0.001) and β-carotene (∆0.51 nmol/L, p = 0.001) at baseline compared to controls. Urine and blood biomarkers of oxidative stress and antioxidant levels showed similar response to vigorous exercise in the SCI and control group. Conclusions: SCI participants showed similar changes in redox status during high intensity exercise compared to matched able-bodied. SCI participants had lower levels of exogen antioxidants both before, during and after vigorous exercise.

• Barin, Agnese; Das, Ranjit K.; Bastani, Nasser Ezzatkhah; Iversen, Per Ole & Duttaroy, Asim Kanti (2023). Extracts of tamarillo, horned melon, and raspberry, but not extract of pear, inhibit human blood platelet aggregation: Investigating the underlying factors for their differential mechanisms. Journal of Functional Foods. ISSN 1756-4646. 110. doi: 10.1016/j.jff.2023.105847. Full text in Research Archive Show summary

  In addition to their roles in thrombosis, hyperactive platelets contribute to atherosclerosis. Since anti-platelet drugs are not recommended for the vulnerable population with hyperactive platelets to reduce the risk of cardiovascular disease, a search is on to find alternative dietary antiplatelets that can be safely used. We here describe that in a dose-dependent manner, sugar-free extracts of tamarillo, horned melon (kiwano), and raspberry inhibited ADP-induced platelet aggregation in platelet-rich plasma, whereas pear extract had no effects. Furthermore, analysis of untargeted metabolites revealed the presence of platelet inhibitory components such as benzoic acid, caffeic acid, and gallic acid in the sugar-free extracts of tamarillo, raspberry, and kiwano but absent in pear extract. All these three fruit extracts inhibited the platelet production of TxB2 and the release of platelet factor 4. Our work suggests that these fruits inhibit platelet aggregation partly due to anti-platelet compounds such as benzoic, caffeic, and gallic acids.

• Clauss, Matthieu; Skattebo, Øyvind; Dæhli, Malin Rasen; Valsdottir, Thorhildur Ditta; Bastani, Nasser Ezzatkhah & Johansen, Egil Ivar [Show all 9 contributors for this article] (2023). Carbohydrate Ingestion during Prolonged Cycling Improves Next-Day Time Trial Performance and Alters Amino Acid Concentrations. Medicine & Science in Sports & Exercise. ISSN 0195-9131. 55(12), p. 2228–2240. doi: 10.1249/MSS.0000000000003264. Full text in Research Archive
• Tore, Elena C.; Eussen, Simone; Bastani, Nasser Ezzatkhah; Dagnelie, Pieter; Elshorbagy, Amany K & Grootswagers, Pol [Show all 14 contributors for this article] (2023). The Associations of Habitual Intake of Sulfur Amino Acids, Proteins and Diet Quality with Plasma Sulfur Amino Acid Concentrations: The Maastricht Study. Journal of Nutrition. ISSN 0022-3166. 153(7), p. 2027–2040. doi: 10.1016/j.tjnut.2023.05.008. Full text in Research Archive
• 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.

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

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

• Wu, Yuanyuan; Smith, A. David; Bastani, Nasser Ezzatkhah; Refsum, Helga & Kwok, Timothy (2022). The dihydrofolate reductase 19-bp deletion modifies the beneficial effect of B-vitamin therapy in mild cognitive impairment: Pooled study of two randomized placebo-controlled trials. Human Molecular Genetics. ISSN 0964-6906. 31(7), p. 1151–1158. doi: 10.1093/hmg/ddab246. Full text in Research Archive Show summary

  Abstract Background: Higher serum homocysteine is associated with cognitive decline in older people. But homocysteine-lowering trials including folic acid (FA) show inconsistent results on cognitive decline. The reduction of FA to dihydrofolate by dihydrofolate reductase (DHFR) is slow in humans. Objective: We examined the effects of the DHFR 19-bp deletion/insertion (del/ins) polymorphism on FA-containing treatment on cognitive decline and brain atrophy in older people with mild cognitive impairment (MCI). Methods: This study used pooled data from two randomized B-vitamin trials on 545 MCI subjects who received either FA-containing B vitamins or placebo for 24 months. Subjects were typed for the DHFR genotype. Primary outcome was the Clinical Dementia Rating scale-global score (CDR-global). Secondary outcomes were CDR-sum of boxes score (CDR-SOB), memory and executive Z-scores and whole brain atrophy rate by serial MRI. Results: The proportions of subjects with del/del, del/ins and ins/ins genotype were 29.5, 44.3 and 26.1%, respectively. DHFR genotypes modified the effects of B vitamins on CDR-global, CDR-SOB and executive function Z-score (Pinteraction = 0.017, 0.014 and 0.052, respectively), with significant benefits being observed only in those with ins/ins genotype (Beta = −1.367, −0.614 and 0.315, P = 0.004, 0.014 and 0.012, respectively). The interaction was not significant for memory Z-score and whole brain atrophy rate. Notably, the supplements only slowed brain atrophy in members of the ‘ins/ins’ group who were not using aspirin. Conclusions: Our data indicate that the beneficial effects of B vitamins including FA on cognitive function are only apparent in those with ins/ins genotype, i.e. relatively better preserved DHFR activity.

• Wik, Jonas Aakre; Chowdhury, Azazul Islam; Kolan, Shrikant; Bastani, Nasser Ezzatkhah; Li, Gaoyang & Alam, Kazi [Show all 8 contributors for this article] (2022). Endogenous glutamine is rate-limiting for anti-CD3 and anti-CD28 induced CD4+ T-cell proliferation and glycolytic activity under hypoxia and normoxia. Biochemical Journal. ISSN 0264-6021. 479(11), p. 1221–1235. doi: 10.1042/BCJ20220144. Full text in Research Archive Show summary

  To meet the demand for energy and biomass, T lymphocytes (T cells) activated to proliferation and clonal expansion, require uptake and metabolism of glucose (Gluc) and the amino acid (AA) glutamine (Gln). Whereas exogenous Gln is converted to glutamate (Glu) by glutaminase (GLS), Gln is also synthesized from the endogenous pool of AA through Glu and activity of glutamine synthase (GS). Most of this knowledge comes from studies on cell cultures under ambient oxygen conditions (normoxia, 21% O2). However, in vivo, antigen induced T-cell activation often occurs under moderately hypoxic (1–4% O2) conditions and at various levels of exogenous nutrients. Here, CD4+ T cells were stimulated for 72 h with antibodies targeting the CD3 and CD28 markers at normoxia and hypoxia (1% O2). This was done in the presence and absence of the GLS and GS inhibitors, Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl) ethyl sulfide (BPTES) and methionine sulfoximine (MSO) and at various combinations of exogenous Gluc, Gln and pyruvate (Pyr) for the last 12 h of stimulation. We found that T-cell proliferation, viability and levels of endogenous AA were significantly influenced by the availability of exogenous Gln, Gluc and Pyr as well as inhibition of GLS and GS. Moreover, inhibition of GLS and GS and levels of oxygen differentially influenced oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Finally, BPTES-dependent down-regulation of ECAR was associated with reduced hexokinase (HK) activity at both normoxia and hypoxia. Our results demonstrate that Gln availability and metabolism is rate-limiting for CD4+ T-cell activity.

• Telle-Hansen, Vibeke; Gaundal, Line; Bastani, Nasser Ezzatkhah; Rud, Ida; Byfuglien, Marte G. & Gjøvaag, Terje [Show all 10 contributors for this article] (2022). Replacing saturated fatty acids with polyunsaturated fatty acids increases the abundance of Lachnospiraceae and is associated with reduced total cholesterol levels-a randomized controlled trial in healthy individuals. Lipids in Health and Disease. 21, p. 1–13. doi: 10.1186/s12944-022-01702-1. Full text in Research Archive Show summary

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

• Nichenametla, Sailendra N.; Mattocks, Dwight A.L.; Cooke, Diana; Midya, Vishal; Malloy, Virginia L. & Mansilla, Wilfredo [Show all 18 contributors for this article] (2022). Cysteine restriction-specific effects of sulfur amino acid restriction on lipid metabolism. Aging Cell. ISSN 1474-9718. 21(12). doi: 10.1111/acel.13739. Full text in Research Archive Show summary

  Decreasing the dietary intake of methionine exerts robust anti-adiposity effects in rodents but modest effects in humans. Since cysteine can be synthesized from methionine, animal diets are formulated by decreasing methionine and eliminating cysteine. Such diets exert both methionine restriction (MR) and cysteine restriction (CR), that is, sulfur amino acid restriction (SAAR). Contrarily, SAAR diets formulated for human consumption included cysteine, and thus might have exerted only MR. Epidemiological studies positively correlate body adiposity with plasma cysteine but not methionine, suggesting that CR, but not MR, is responsible for the anti-adiposity effects of SAAR. Whether this is true, and, if so, the underlying mechanisms are unknown. Using methionine- and cysteine-titrated diets, we demonstrate that the anti-adiposity effects of SAAR are due to CR. Data indicate that CR increases serinogenesis (serine biosynthesis from non-glucose substrates) by diverting substrates from glyceroneogenesis, which is essential for fatty acid reesterification and triglyceride synthesis. Molecular data suggest that CR depletes hepatic glutathione and induces Nrf2 and its downstream targets Phgdh (the serine biosynthetic enzyme) and Pepck-M. In mice, the magnitude of SAAR-induced changes in molecular markers depended on dietary fat concentration (60% fat >10% fat), sex (males > females), and age-at-onset (young > adult). Our findings are translationally relevant as we found negative and positive correlations of plasma serine and cysteine, respectively, with triglycerides and metabolic syndrome criteria in a cross-sectional epidemiological study. Controlled feeding of low-SAA, high-polyunsaturated fatty acid diets increased plasma serine in humans. Serinogenesis might be a target for treating hypertriglyceridemia.

• Elshorbagy, Amany K.; Turner, Cheryl; Bastani, Nasser Ezzatkhah; Refsum, Helga & Kwok, Timothy (2022). The association of serum sulfur amino acids and related metabolites with incident diabetes: a prospective cohort study. European Journal of Nutrition. ISSN 1436-6207. 61, p. 3161–3173. doi: 10.1007/s00394-022-02872-5. Full text in Research Archive
• Elshorbagy, Amany; Bastani, Nasser Ezzatkhah; Lee-Ødegård, Sindre; Øvrebø, Bente; Yasein, Nadia Haj & Svendsen, Karianne [Show all 10 contributors for this article] (2022). The association of fasting plasma thiol fractions with body fat compartments, biomarker profile, and adipose tissue gene expression. Amino Acids. ISSN 0939-4451. doi: 10.1007/s00726-022-03229-2. Full text in Research Archive Show summary

  Abstract People with high plasma total cysteine (tCys) have higher fat mass and higher concentrations of the atherogenic apolipoprotein B (apoB). The disulfide form, cystine, enhanced human adipogenesis and correlated with total fat mass in a Middle-Eastern cohort. In 35 European adults with overweight (88.6% women) and with dual-X-ray absorptiometry measurements of regional fat, we investigated how cystine compared to other free disulfides in their association with total regional adiposity, plasma lipid and glucose biomarkers, and adipose tissue lipid enzyme mRNA ( n  = 19). Most total plasma homocysteine (tHcy) (78%) was protein-bound; 63% of total glutathione (tGSH) was reduced. tCys was 49% protein-bound, 30% mixed-disulfide, 15% cystine, and 6% reduced. Controlling for age and lean mass, cystine and total free cysteine were the fractions most strongly associated with android and total fat: 1% higher cystine predicted 1.97% higher android fat mass (95% CI 0.64, 3.31) and 1.25% (0.65, 2.98) higher total fat mass (both p  = 0.005). A positive association between tCys and apoB ( β : 0.64%; 95% CI 0.17, 1.12%, p  = 0.009) was apparently driven by free cysteine and cystine; cystine was also inversely associated with the HDL-associated apolipoprotein A1 ( β : −0.57%; 95% CI −0.96, −0.17%, p  = 0.007). No independent positive associations with adiposity were noted for tGSH or tHcy fractions. Plasma cystine correlated with CPT1a mRNA (Spearman’s r  = 0.68, p  = 0.001). In conclusion, plasma cystine—but not homocysteine or glutathione disulfides—is associated with android adiposity and an atherogenic plasma apolipoprotein profile. The role of cystine in human adiposity and cardiometabolic risk deserves investigation. ClinicalTrials.gov identifiers: NCT02647970 and NCT03629392.

• Bøhn, Siv Kjølsrud; Myhrstad, Mari; Thoresen, Magne; Erlund, Iris; Vasstrand, Ann Kristin & Marciuch, Anne [Show all 11 contributors for this article] (2021). Bilberry/red grape juice decreases plasma biomarkers of inflammation and tissue damage in aged men with subjective memory impairment –a randomized clinical trial. BMC Nutrition. 7(75). doi: 10.1186/s40795-021-00482-8. Full text in Research Archive Show summary

  Background: Few randomized clinical trials have explored the health effects of bilberries in humans. The aim was to test the effect of bilberry and red grape-juice consumption on visual memory, motor speed and dexterity as well as inflammatory and tissue damage biomarkers of plasma in aged men with subjective memory impairment. Methods: Nine-week double-blind, placebo-controlled, dietary intervention study of aged men (n = 60, age ≥ 67 years) with subjective memory impairment randomized to consume a 50/50 mix of bilberry/red grape-juice or an iso-caloric placebo juice. A selection of Cambridge Cognition Test Battery (CANTAB), Grooved Pegboard tests and blood-sampling for biomarker analysis were performed before and after the intervention. Results: Compared to placebo the selected memory and motor test scores were un-affected by the bilberry/red grape intervention. However, the plasma levels of tissue damage biomarkers decreased significantly more in the bilberry/red grape group. In particular lactate dehydrogenase (LDH) decreased from 362 U/L (median, baseline) to 346 U/L (median, post intervention) in the bilberry/red grape group. Also, several biomarkers of inflammation (EGF, IL6, IL9, IL10 and TNFα) decreased significantly more in the bilberry/red grape group. Furthermore, several plasma polyphenols; p-coumaric acid, hippuric acid, protocatechuic acid, 3HPAA and vanillic acid, increased significantly more in the bilberry/red grape group compared to placebo with the largest increase in p-coumaric acid with 116%; from 2.2 [1.0,5.5] to 4.7 [2.8,8.1] μM/L (median [95% CL]). Conclusions: The results indicate that a nine-week bilberry/red grape juice intervention has no measurable effects on the selected memory scores in aged men experiencing memory problems but decreases the level of biomarkers of inflammation and tissue damage. Whether the dampening effects on inflammation and tissue damage biomarkers have relevance for neuroinflammatory brain pathology remains to be established.

• Olsen, Thomas; Øvrebø, Bente; Turner, Cheryl; Bastani, Nasser Ezzatkhah; Refsum, Helga & Vinknes, Kathrine (2021). Effects of short-term methionine and cysteine restriction and enrichment with polyunsaturated fatty acids on oral glucose tolerance, plasma amino acids, fatty acids, lactate and pyruvate: results from a pilot study. BMC Research Notes. 14(43). doi: 10.1186/s13104-021-05463-5. Full text in Research Archive Show summary

  Objective In this 7-day pilot study we randomized healthy, normal-weight men and women to either a dietary intervention with methionine and cysteine restriction enriched in PUFA (Met/Cyslow + PUFA, n = 7) or with high contents of methionine, cysteine and SFA (Met/Cyshigh + SFA, n = 7). The objective was to describe the short-term responses in oral glucose tolerance, amino acid profile, total fatty acid profile, pyruvate and lactate following a Met/Cyslow + PUFA diet vs. Met/Cyshigh + SFA. Results The diet groups consisted of five women and two men, aged 20–38 years. After the 7-d intervention median pre- and post-oral glucose tolerance test (OGTT) glucose concentrations were 5 mmol/L and 4 mmol/L respectively in the Met/Cyslow + PUFA group. In the Met/Cyshigh + SFA group, median pre- and post-OGTT glucose concentrations were 4.8 mmol/L and 4.65 mmol/L after the 7-d intervention. The responses in the amino acid profiles were similar in both groups during the intervention with the exception of serine. Fatty acids decreased from baseline to day 7 in both groups. Plasma lactate and pyruvate were similar for both groups with an increase to day 3 before approaching baseline values at day 7. Trial registration ClinicalTrials.gov: NCT02647970, registration date: January 6th 2016.

• Olsen, Thomas; Turner, Cheryl; Øvrebø, Bente; Bastani, Nasser Ezzatkhah; Refsum, Helga & Vinknes, Kathrine (2020). Postprandial effects of a meal low in sulfur amino acids and high in polyunsaturated fatty acids compared to a meal high in sulfur amino acids and saturated fatty acids on stearoyl CoA-desaturase indices and plasma sulfur amino acids: a pilot study. BMC Research Notes. 13. doi: 10.1186/s13104-020-05222-y. Full text in Research Archive Show summary

  Objective The sulfur amino acid (SAA) cysteine is positively related, whereas polyunsaturated fatty acids (PUFAs) are inversely related to activity of the lipogenic enzyme stearoyl-CoA desaturase (SCD). High SCD activity promotes obesity in animals, and plasma activity indices positively associates with fat mass in humans. SCD may thus be a target for dietary intervention with SAA restriction and PUFA enrichment with unknown potential benefits for body composition. We randomized ten healthy individuals to a meal restricted in SAAs and enriched with PUFAs (Cys/Metlow + PUFA) (n = 5) or a meal enriched in SAA and saturated fatty acids (Cys/Methigh + SFA) (n = 5). We measured plasma SCD activity indices (SCD16 and SCD18) and SAAs response hourly from baseline and up to 4 h postprandial. Results SCD16 was unchanged whereas SCD18 tended to increase in the Cys/Metlow + PUFA compared to the Cys/Methigh + SFA group (ptime*group interaction = 0.08). Plasma concentrations of total cysteine fractions including free and reduced cysteine decreased in the Cys/Metlow + PUFA compared to the Cys/Methigh + SFA group (both ptime*group interaction < 0.001). In conclusion, a meal low in SAA but high in PUFAs reduced plasma cysteine fractions but not SCD activity indices. This pilot study can be useful for the design and diet composition of future dietary interventions that targets SCD and SAA. Trial registration ClinicalTrials.gov: NCT02647970, registration date: 6 January 2016

• Olsen, Thomas; Øvrebø, Bente; Yasein, Nadia Haj; Lee-Ødegård, Sindre; Svendsen, Karianne & Hjorth, Marit [Show all 11 contributors for this article] (2020). Effects of dietary methionine and cysteine restriction on plasma biomarkers, serum fibroblast growth factor 21, and adipose tissue gene expression in women with overweight or obesity: a double-blind randomized controlled pilot study. Journal of Translational Medicine. 18(122). doi: 10.1186/s12967-020-02288-x. Full text in Research Archive Show summary

  Background Dietary restriction of methionine and cysteine is a well-described model that improves metabolic health in rodents. To investigate the translational potential in humans, we evaluated the effects of dietary methionine and cysteine restriction on cardiometabolic risk factors, plasma and urinary amino acid profile, serum fibroblast growth factor 21 (FGF21), and subcutaneous adipose tissue gene expression in women with overweight and obesity in a double-blind randomized controlled pilot study. Methods Twenty women with overweight or obesity were allocated to a diet low (Met/Cys-low, n = 7), medium (Met/Cys-medium, n = 7) or high (Met/Cys-high, n = 6) in methionine and cysteine for 7 days. The diets differed only by methionine and cysteine content. Blood and urine were collected at day 0, 1, 3 and 7 and subcutaneous adipose tissue biopsies were taken at day 0 and 7. Results Plasma methionine and cystathionine and urinary total cysteine decreased, whereas FGF21 increased in the Met/Cys-low vs. Met/Cys-high group. The Met/Cys-low group had increased mRNA expression of lipogenic genes in adipose tissue including DGAT1. When we excluded one participant with high fasting insulin at baseline, the Met/Cys-low group showed increased expression of ACAC, DGAT1, and tendencies for increased expression of FASN and SCD1 compared to the Met/Cys-high group. The participants reported satisfactory compliance and that the diets were moderately easy to follow. Conclusions Our data suggest that dietary methionine and cysteine restriction may have beneficial effects on circulating biomarkers, including FGF21, and influence subcutaneous adipose tissue gene expression. These results will aid in the design and implementation of future large-scale dietary interventions with methionine and cysteine restriction. Trial registration ClinicalTrials.gov Identifier: NCT03629392, registration date: 14/08/2018 https://clinicaltrials.gov/ct2/show/NCT03629392.

• Henjum, Sigrun; Manger, Mari Skar; Hampel, Daniela; Brantsæter, Anne Lise; Shahab-Ferdows, Setareh & Bastani, Nasser Ezzatkhah [Show all 9 contributors for this article] (2020). Vitamin B12 concentrations in milk from Norwegian women during the six first months of lactation. European Journal of Clinical Nutrition. ISSN 0954-3007. 74(5), p. 749–756. doi: 10.1038/s41430-020-0567-x. Full text in Research Archive Show summary

  Background: Human milk vitamin B12 (B12) concentrations depend on maternal status and intake; only few data are available in high-income countries. Objective: We assessed human milk B12 concentrations during the first 6 months postpartum in Norwegian women and its association with maternal dietary B12 intake and maternal urinary methylmalonic acid (MMA) concentration. Methods: In this cross-sectional study, 175 mothers, exclusively (80%) or partially (20%) breastfeeding, were included. Milk B12 was measured by IMMULITE®/IMMULITE® 1000 B12 competitive protein binding assay and urinary MMA relative to creatinine (MMA/Cr) by liquid chromatography-tandem-mass spectrometry. Maternal habitual B12 intake and supplement use were estimated using a food frequency questionnaire. Results: Mean human milk B12 concentration was 327 pmol/L (range 140-1089), with 402 pmol/L at 1 month (n = 21), 333 pmol/L at four months (n = 32), and 299 pmol/L at 6 months (n = 21). Maternal B12 intake was 5 µg/d, 89% met the Estimated Average Requirement, and supplement use did not affect milk B12 concentrations. MMA/Cr was low in all women compared with published data. In exclusively breastfeeding women, MMA/Cr (beta (95% CI) -42.5 (-82.5, -2.5) and time since birth (-4.9 (-9.6, -0.3)) were significant predictors of human milk B12 concentrations. There was no association between total B12 intake and milk B12 concentration or between total B12 intake and MMA/Cr. Conclusions: Maternal B12 status and human milk B12 concentrations are likely sufficient, based on adequate maternal B12 dietary intake combined with low urinary MMA concentrations. Nevertheless, milk B12 concentration fell during 6 months postpartum while maternal B12 status did not change.

• Koivisto-Mørk, Anu; Paur, Ingvild; Paulsen, Gøran; Garthe, Ina; Raastad, Truls & Bastani, Nasser Ezzatkhah [Show all 8 contributors for this article] (2020). Dietary Adjustments to Altitude Training in Elite Endurance Athletes; Impact of a Randomized Clinical Trial With Antioxidant-Rich Foods. Frontiers in Sports and Active Living. 2. doi: 10.3389/fspor.2020.00106. Full text in Research Archive Show summary

  Background: Altitude training stresses several physiological and metabolic processes and alters the dietary needs of the athletes. International Olympic Committee (IOC)'s Nutrition Expert Group suggests that athletes should increase intake of energy, carbohydrate, iron, fluid, and antioxidant-rich foods while training at altitude. Objective: We investigated whether athletes adjust their dietary intake according to the IOC's altitude-specific dietary recommendations, and whether an in-between meal intervention with antioxidant-rich foods altered the athletes' dietary composition and nutrition-related blood parameters (mineral, vitamin, carotenoid, and hormone concentrations). Design: The dietary adjustments to altitude training (3 weeks at 2,320 m) were determined for 31 elite endurance athletes (23 ± 5 years, 23 males, 8 females) by six interviewer-administered 24-h dietary recalls on non-consecutive days; three before and during the altitude camp. The additional effect of in -between meal intervention with eucaloric antioxidant-rich or control snacks (1,000 kcal/day) was tested in a randomized controlled trial with parallel design. Results: At altitude the athletes increased their energy intake by 35% (1,430 ± 630 kcal/day, p < 0.001), the provided snacks accounting for 70% of this increase. Carbohydrate intake increased from 6.5 ± 1.8 g/kg body weight (BW) (50 E%) to 9.3 ± 2.1 g/kg BW (53 E%) (p < 0.001), with no difference between the antioxidant and control group. Dietary iron, fluid, and antioxidant-rich food intake increased by 37, 38, and 104%, respectively, in the whole cohort. The intervention group had larger increases in polyunsaturated fatty acids (PUFA), ω3 PUFA (n-3 fatty acids), ω6 PUFA (n-6 fatty acids), fiber, vitamin C, folic acid, and copper intake, while protein intake increased more among the controls, reflecting the nutritional content of the snacks. Changes in the measured blood minerals, vitamins, and hormones were not differentially affected by the intervention except for the carotenoid; zeaxanthin, which increased more in the intervention group (p < 0.001). Conclusions: Experienced elite endurance athletes increased their daily energy, carbohydrate, iron, fluid, and antioxidant-rich food intake during a 3-week training camp at moderate altitude meeting most of the altitude-specific dietary recommendations. The intervention with antioxidant-rich snacks improved the composition of the athletes' diets but had minimal impact on the measured nutrition-related blood parameters.

• Koivisto, Anu; Olsen, Thomas; Paur, Ingvild; Paulsen, Gøran; Bastani, Nasser Ezzatkhah & Garthe, Ina [Show all 10 contributors for this article] (2019). Effects of antioxidant-rich foods on altitude-induced oxidative stress and inflammation in elite endurance athletes: A randomized controlled trial. PLOS ONE. 14(6). doi: 10.1371/journal.pone.0217895. Full text in Research Archive Show summary

  Background Various altitude training regimes, systematically used to improve oxygen carrying capacity and sports performance, have been associated with increased oxidative stress and inflammation. We investigated whether increased intake of common antioxidant-rich foods attenuates these processes. Methods In a randomized controlled trial, 31 elite endurance athletes (23 ± 5 years), ingested antioxidant-rich foods (n = 16), (> doubling their usual intake), or eucaloric control foods (n = 15) during a 3-week altitude training camp (2320 m). Fasting blood and urine samples were collected 7 days pre-altitude, after 5 and 18 days at altitude, and 7 days post-altitude. Change over time was compared between the groups using mixed models for antioxidant capacity [uric acid-free (ferric reducing ability of plasma (FRAP)], oxidative stress (8-epi-PGF2α) and inflammatory biomarkers (IFNγ, IL1α, IL1RA, IL1β, IL2, IL5, IL6, IL7, IL10, IL12p70, IL13, IL17, TNFα, MCP-1 and micro-CRP). The cytokine response to a stress-test (VO2max ramp test or 100 m swimming) was assessed at pre- and post-altitude. Results FRAP increased more in the antioxidant compared to the control group (p = 0.034). IL13 decreased in the antioxidant group, while increasing in the controls (p = 0.006). A similar trend was seen for IL6 (p = 0.062). A larger decrease in micro-CRP was detected in the antioxidant group compared to controls (β: -0.62, p = 0.02). We found no group differences for the remaining cytokines. 8-epi-PGF2α increased significantly in the whole population (p = 0.033), regardless group allocation. The stress response was significantly larger post-altitude compared with pre-altitude for IL1β, IL6, IL7, IL13, IL12p70 and TNFα, but we found no group differences. Conclusions Increased intake of antioxidant-rich foods elevated the antioxidant capacity and attenuated some of the altitude-induced systemic inflammatory biomarkers in elite athletes. The antioxidant intervention had no impact on the altitude-induced oxidative stress or changes in acute cytokine responses to exercise stress-tests.

• Olsen, Thomas; Øvrebø, Bente; Turner, Cheryl; Bastani, Nasser Ezzatkhah; Refsum, Helga & Vinknes, Kathrine (2018). Combining Dietary Sulfur Amino Acid Restriction with Polyunsaturated Fatty Acid Intake in Humans: A Randomized Controlled Pilot Trial. Nutrients. 10(12), p. 1–15. doi: 10.3390/nu10121822. Full text in Research Archive
• Koivisto, Anu; Paulsen, Gøran; Paur, Ingvild; Garthe, Ina; Tønnessen, Espen & Raastad, Truls [Show all 10 contributors for this article] (2018). Antioxidant-rich foods and response to altitude training: A randomized controlled trial in elite endurance athletes. Scandinavian Journal of Medicine & Science in Sports. ISSN 0905-7188. 28(9), p. 1982–1995. doi: 10.1111/sms.13212. Full text in Research Archive Show summary

  High doses of isolated antioxidant supplements such as vitamin C and E have demonstrated the potential to blunt cellular adaptations to training. It is, however, unknown whether intake of high doses of antioxidants from foods has similar effects. Hence, the aim of the study was to investigate whether intake of antioxidant‐rich foods affects adaptations to altitude training in elite athletes. In a randomized controlled trial, 31 national team endurance athletes (23 ± 5 years) ingested antioxidant‐rich foods (n = 16) or eucaloric control foods (n = 15) daily during a 3‐week altitude training camp (2320 m). Changes from baseline to post‐altitude in hemoglobin mass (Hbmass; optimized CO rebreathing), maximal oxygen uptake (VO2max; n = 16) or 100 m swimming performance (n = 10), and blood parameters were compared between the groups. The antioxidant group significantly increased total intake of antioxidant‐rich foods (~118%) compared to the control group during the intervention. The total study population improved VO2max by 2.5% (1.7 mL/kg/min, P = .006) and Hbmass by 4.7% (48 g, P < .001), but not 100 m swimming performance. No difference was found between the groups regarding changes in Hbmass, VO2max or swimming performance. However, hemoglobin concentration increased more in the antioxidant group (effect size = 0.7; P = .045) with a concomitantly larger decrease in plasma and blood volumes compared to control group. Changes in ferritin and erythropoietin from pre‐ to post‐altitude did not differ between the groups. Doubling the intake of antioxidant‐rich foods was well tolerated and did not negatively influence the adaptive response to altitude training in elite endurance athletes.

• Holm, Maia Blomhoff; Kristiansen, Oddrun; Holme, Ane Moe; Bastani, Nasser Ezzatkhah; Horne, Hildegunn & Blomhoff, Rune [Show all 9 contributors for this article] (2018). Placental release of taurine to both the maternal and fetal circulations in human term pregnancies. Amino Acids. ISSN 0939-4451. 50(9), p. 1205–1214. doi: 10.1007/s00726-018-2576-9. Full text in Research Archive Show summary

  Taurine is regarded as an essential amino acid in utero, and fetal taurine supply is believed to rely solely on placental transfer from maternal plasma. Despite its potential role in intrauterine growth restriction and other developmental disturbances, human in vivo studies of taurine transfer between the maternal, placental, and fetal compartments are scarce. We studied placental transfer of taurine in uncomplicated human term pregnancies in vivo in a cross-sectional study of 179 mother-fetus pairs. During cesarean section, we obtained placental tissue and plasma from incoming and outgoing vessels on the maternal and fetal sides of the placenta. Taurine was measured by liquid chromatography–tandem mass spectrometry. We calculated paired arteriovenous differences, and measured placental expression of the taurine biosynthetic enzyme cysteine sulfinic acid decarboxylase (CSAD) with quantitative real-time polymerase chain reaction and western blot. We observed a fetal uptake (p < 0.001), an uteroplacental release (p < 0.001), and a negative placental consumption of taurine (p = 0.001), demonstrating a bilateral placental release to the maternal and fetal compartments. Increasing umbilical vein concentrations and fetal uptake was associated with the uteroplacental release to the maternal circulation (rs = − 0.19, p = 0.01/rs = − 0.24, p = 0.003), but not with taurine concentrations in placental tissue. CSAD-mRNA was expressed in placental tissue, suggesting a potential for placental taurine synthesis. Our observations show that the placenta has the capacity to a bilateral taurine release, indicating a fundamental role of taurine in the human placental homeostasis beyond the supply to the fetus.

• Hanvold, Susanna; Vinknes, Kathrine; Bastani, Nasser Ezzatkhah; Turner, Cheryl; Løken, Elin Bjørge & Mala, Tom [Show all 8 contributors for this article] (2017). Plasma amino acids, adiposity, and weight change after gastric bypass surgery: are amino acids associated with weight regain? European Journal of Nutrition. ISSN 1436-6207. p. 1–9. doi: 10.1007/s00394-017-1533-9. Full text in Research Archive
• Holm, Maia Blomhoff; Bastani, Nasser Ezzatkhah; Holme, Ane Moe; Zucknick, Manuela; Jansson, Thomas & Refsum, Helga [Show all 10 contributors for this article] (2017). Uptake and release of amino acids in the fetal-placental unit in human pregnancies. PLOS ONE. 12(10). doi: 10.1371/journal.pone.0185760. Full text in Research Archive Show summary

  Objectives: The current concepts of human fetal-placental amino acid exchange and metabolism are mainly based on animal-, in vitro- and ex vivo models. We aimed to determine and assess the paired relationships between concentrations and arteriovenous differences of 19 amino acids on the maternal and fetal sides of the human placenta in a large study sample. Methods: This cross-sectional in vivo study included 179 healthy women with uncomplicated term pregnancies. During planned cesarean section, we sampled blood from incoming and outgoing vessels on the maternal (radial artery and uterine vein) and fetal (umbilical vein and artery) sides of the placenta. Amino acid concentrations were measured by liquid chromatography—tandem mass spectrometry. We calculated paired arteriovenous differences and performed Wilcoxon signed-rank tests and Spearman’s correlations. Results: In the umbilical circulation, we observed a positive venoarterial difference (fetal uptake) for 14 amino acids and a negative venoarterial difference (fetal release) for glutamic acid (p<0.001). In the maternal circulation, we observed a positive arteriovenous difference (uteroplacental uptake) for leucine (p = 0.005), isoleucine (p = 0.01), glutamic acid (p<0.001) and arginine (p = 0.04) and a negative arteriovenous difference (uteroplacental release) for tyrosine (p = 0.002), glycine (p = 0.01) and glutamine (p = 0.02). The concentrations in the maternal artery and umbilical vein were correlated for all amino acids except tryptophan, but we observed no correlations between the uteroplacental uptake and the fetal uptake or the umbilical vein concentration. Two amino acids showed a correlation between the maternal artery concentration and the fetal uptake. Conclusions: Our human in vivo study expands the current insight into fetal-placental amino acid exchange, and discloses some differences from what has been previously described in animals. Our findings are consistent with the concept that the fetal supply of amino acids in the human is the result of a dynamic interplay between fetal and placental amino acid metabolism and interconversions.

• Stea, Tonje Holte; Berntsen, Solvor; Berntsen, Sveinung; Bastani, Nasser Ezzatkhah; Paulsen, Gøran & Seiler, Hilde Lohne [Show all 9 contributors for this article] (2016). Effect of Omega-3 and Vitamins e + C Supplements on the Concentration of Serum B-Vitamins and Plasma Redox Aminothiol Antioxidant Status in Elderly Men after Strength Training for Three Months. Annals of Nutrition and Metabolism. ISSN 0250-6807. 68(2), p. 145–155. doi: 10.1159/000443847. Full text in Research Archive
• Bjørnsen, Thomas; Salvesen, Svein; Berntsen, Sveinung; Hetlelid, Ken Joar; Stea, Tonje Holte & Seiler, Hilde Lohne [Show all 17 contributors for this article] (2015). Vitamin C and E supplementation blunts increases in total lean body mass in elderly men after strength training. Scandinavian Journal of Medicine & Science in Sports. ISSN 0905-7188. 26(7), p. 755–755. doi: 10.1111/sms.12506. Full text in Research Archive Show summary

  The aim of this study was to investigate the effects of vitamin C and E supplementation on changes in muscle mass (lean mass and muscle thickness) and strength during 12 weeks of strength training in elderly men. Thirty-four elderly males (60–81 years) were randomized to either an antioxidant group (500 mg of vitamin C and 117.5 mg vitamin E before and after training) or a placebo group following the same strength training program (three sessions per week). Body composition was assessed with dual-energy X-ray absorptiometry and muscle thickness by ultrasound imaging. Muscle strength was measured as one-repetition maximum (1RM). Total lean mass increased by 3.9% (95% confidence intervals: 3.0, 5.2) and 1.4% (0, 5.4) in the placebo and antioxidant groups, respectively, revealing larger gains in the placebo group (P = 0.04). Similarly, the thickness of m. rectus femoris increased more in the placebo group [16.2% (12.8, 24.1)] than in the antioxidant group [10.9% (9.8, 13.5); P = 0.01]. Increases of lean mass in trunk and arms, and muscle thickness of elbow flexors, did not differ significantly between groups. With no group differences, 1RM improved in the range of 15–21% (P < 0.001). In conclusion, high-dosage vitamin C and E supplementation blunted certain muscular adaptations to strength training in elderly men.

• Kolberg, Marit; Pedersen, Sigrid; Bastani, Nasser Ezzatkhah; Carlsen, Harald; Blomhoff, Rune & Paur, Ingvild (2015). Tomato Paste Alters NF-κB and Cancer-Related mRNA Expression in Prostate Cancer Cells, Xenografts, and Xenograft Microenvironment. Nutrition and Cancer. ISSN 0163-5581. 67(2), p. 305–315. doi: 10.1080/01635581.2015.990575. Full text in Research Archive
• Svendsen, Mette; Tonstad, Serena; Heggen, Eli; Pedersen, Terje Rolf; Seljeflot, Ingebjørg & Bøhn, Siv Kjølsrud [Show all 10 contributors for this article] (2015). The effect of kiwifruit consumption on blood pressure in subjects with moderately elevated blood pressure: A randomized, controlled study. Blood Pressure. ISSN 0803-7051. 24(1), p. 48–54. doi: 10.3109/08037051.2014.976979. Full text in Research Archive
• Sakhi, Amrit Kaur; Bastani, Nasser Ezzatkhah; Ellingjord-Dale, Merete; Gundersen, Thomas Erik; Blomhoff, Rune & Ursin, Giske (2015). Feasibility of self-sampled dried blood spot and saliva samples sent by mail in a population-based study. BMC Cancer. 15(1). doi: 10.1186/s12885-015-1275-0. Full text in Research Archive Show summary

  Background In large epidemiological studies it is often challenging to obtain biological samples. Self-sampling by study participants using dried blood spots (DBS) technique has been suggested to overcome this challenge. DBS is a type of biosampling where blood samples are obtained by a finger-prick lancet, blotted and dried on filter paper. However, the feasibility and efficacy of collecting DBS samples from study participants in large-scale epidemiological studies is not known. The aim of the present study was to test the feasibility and response rate of collecting self-sampled DBS and saliva samples in a population–based study of women above 50 years of age. Methods We determined response proportions, number of phone calls to the study center with questions about sampling, and quality of the DBS. We recruited women through a study conducted within the Norwegian Breast Cancer Screening Program. Invitations, instructions and materials were sent to 4,597 women. The data collection took place over a 3 month period in the spring of 2009. Results Response proportions for the collection of DBS and saliva samples were 71.0% (3,263) and 70.9% (3,258), respectively. We received 312 phone calls (7% of the 4,597 women) with questions regarding sampling. Of the 3,263 individuals that returned DBS cards, 3,038 (93.1%) had been packaged and shipped according to instructions. A total of 3,032 DBS samples were sufficient for at least one biomarker analysis (i.e. 92.9% of DBS samples received by the laboratory). 2,418 (74.1%) of the DBS cards received by the laboratory were filled with blood according to the instructions (i.e. 10 completely filled spots with up to 7 punches per spot for up to 70 separate analyses). To assess the quality of the samples, we selected and measured two biomarkers (carotenoids and vitamin D). The biomarker levels were consistent with previous reports. Conclusion Collecting self-sampled DBS and saliva samples through the postal services provides a low cost, effective and feasible alternative in epidemiological studies.

• Kvaavik, Elisabeth; Totland, Torunn Holm; Bastani, Nasser Ezzatkhah; Kjøllesdal, Marte Karoline Råberg; Tell, Grethe S & Andersen, Lene Frost (2014). Do smoking and fruit and vegetable intake mediate the association between socio-economic status and plasma carotenoids? European Journal of Public Health. ISSN 1101-1262. 24(4), p. 685–690. doi: 10.1093/eurpub/ckt081. Full text in Research Archive Show summary

  Background: The aim was to study whether the association between educational attainment and antioxidant status is mediated by smoking and fruit and vegetable intake. Methods: Cross-sectional analyses of the Oslo Youth Study 2006 wave were carried out. Information about education, smoking habits and diet was collected by questionnaire for 261 subjects (142 women and 119 men aged 38–42 years). Blood samples, height and weight measurements were taken by the participants’ General Practitioner. Blood were analysed for plasma carotenoids. Linear regression analyses were used to examine whether smoking and fruit and vegetable intake mediate the association between education and plasma carotenoids. Results: Educational level was positively associated with β-cryptoxanthin, α-carotene and lutein/zeaxanthin, but not with total carotenoids, β-carotene or lycopene. Education was negatively associated with smoking and positively associated with fruit and vegetable intake. Smoking was negatively associated with β-cryptoxanthin, and fruit and vegetable intake was positively associated with β-cryptoxanthin (adjusted for educational level). Moreover, cigarette consumption mediated the association between education and β-cryptoxanthin by 37%, while fruit and vegetable intake mediated this association by 18%. The total mediation effect was 55%. Conclusion: Smoking seemed to be more important as a mediator between education and plasma levels of β-cryptoxanthin than the intake of fruit and vegetables, but more studies are needed to establish the relative importance of smoking and diet as mediators of the association between education and antioxidant status.

• Dizdarevic, Lili Leko; Biswas, Dipankar; Uddin, Main; Jørgensen, Aud Jeanette; Falch, Eva & Bastani, Nasser Ezzatkhah [Show all 7 contributors for this article] (2014). Inhibitory effects of kiwifruit extract on human platelet aggregation and plasma angiotensin-converting enzyme activity. Platelets. ISSN 0953-7104. 25(8), p. 567–575. doi: 10.3109/09537104.2013.852658. Full text in Research Archive
• Cumming, Kristoffer Toldnes; Raastad, Truls; Holden, Geir; Bastani, Nasser Ezzatkhah; Schneeberger, Damaris & Paronetto, Maria Paola [Show all 12 contributors for this article] (2014). Effects of vitamin C and E supplementation on endogenous antioxidant systems and heat shock proteins in response to endurance training. Physiological Reports. 2(10). doi: 10.14814/phy2.12142. Full text in Research Archive Show summary

  Reactive oxygen and nitrogen species are important signal molecules for adaptations to training. Due to the antioxidant properties of vitamin C and E, supplementation has been shown to blunt adaptations to endurance training. In this study, we investigated the effects of vitamin C and E supplementation and endurance training on adaptations in endogenous antioxidants and heat shock proteins (HSP). Thirty seven males and females were randomly assigned to receive Vitamin C and E (C + E; C: 1000 mg, E: 235 mg daily) or placebo (PLA), and underwent endurance training for 11 weeks. After 5 weeks, a subgroup conducted a high intensity interval session to investigate acute stress responses. Muscle and blood samples were obtained to investigate changes in proteins and mRNA related to the antioxidant and HSP system. The acute response to the interval session revealed no effects of C + E supplementation on NFκB activation. However, higher stress responses to exercise in C + E group was indicated by larger translocation of HSPs and a more pronounced gene expression compared to PLA. Eleven weeks of endurance training decreased muscle GPx1, HSP27 and αB‐crystallin, while mnSOD, HSP70 and GSH remained unchanged, with no influence of supplementation. Plasma GSH increased in both groups, while uric acid decreased in the C + E group only. Our results showed that C + E did not affect long‐term training adaptations in the antioxidant‐ and HSP systems. However, the greater stress responses to exercise in the C + E group might indicate that long‐term adaptations occurs through different mechanisms in the two groups.

• Bilbija, Dusan; Elmabsout, Ali Ateia; Sagave, Julia Fritzi; Haugen, Fred; Bastani, Nasser Ezzatkhah & Dahl, Christen Peder [Show all 10 contributors for this article] (2014). Expression of retinoic acid target genes in coronary artery disease. International Journal of Molecular Medicine. ISSN 1107-3756. 33(3), p. 677–686. doi: 10.3892/ijmm.2014.1623. Full text in Research Archive
• Paulsen, Gøran; Cumming, Kristoffer T.; Holden, Geir; Hallén, Jostein; Rønnestad, Bent & Sveen, Ole [Show all 19 contributors for this article] (2014). Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind randomized controlled trial. Journal of Physiology. ISSN 0022-3751. 592(8), p. 1887–1901. doi: 10.1113/jphysiol.2013.267419. Full text in Research Archive Show summary

  In this double-blind, randomised, controlled trial, we investigated the effects of vitamin C and E supplementation on endurance training adaptations in humans. Fifty-four young men and women were randomly allocated to receive either 1000 mg of vitamin C and 235 mg of vitamin E or a placebo daily for 11 weeks. During supplementation, the participants completed an endurance training programme consisting of three to four sessions per week (primarily of running), divided into high-intensity interval sessions [4-6 × 4-6 min; >90% of maximal heart rate (HRmax)] and steady state continuous sessions (30-60 min; 70-90% of HRmax). Maximal oxygen uptake (VO2 max ), submaximal running and a 20 m shuttle run test were assessed and blood samples and muscle biopsies were collected, before and after the intervention. Participants in the vitamin C and E group increased their VO2 max (mean ± s.d.: 8 ± 5%) and performance in the 20 m shuttle test (10 ± 11%) to the same degree as those in the placebo group (mean ± s.d.: 8 ± 5% and 14 ± 17%, respectively). However, the mitochondrial marker cytochrome c oxidase subunit IV (COX4) and cytosolic peroxisome proliferator-activated receptor-γ coactivator 1 α (PGC-1α) increased in the m. vastus lateralis in the placebo group by 59 ± 97% and 19 ± 51%, respectively, but not in the vitamin C and E group (COX4: -13 ± 54%; PGC-1α: -13 ± 29%; P ≤ 0.03, between groups). Furthermore, mRNA levels of CDC42 and mitogen-activated protein kinase 1 (MAPK1) in the trained muscle were lower in the vitamin C and E group than in the placebo group (P ≤ 0.05). Daily vitamin C and E supplementation attenuated increases in markers of mitochondrial biogenesis following endurance training. However, no clear interactions were detected for improvements in VO2 max and running performance. Consequently, vitamin C and E supplementation hampered cellular adaptations in the exercised muscles, and although this did not translate to the performance tests applied in this study, we advocate caution when considering antioxidant supplementation combined with endurance exercise.

• Haj-Yasein, Nadia Nabil; Dalen, Knut Tomas; Berg, Ole; Bastani, Nasser Ezzatkhah; Refsum, Helga & Nebb, Hilde Irene (2013). Low Cysteine Interferes With PPARγ Activity And Reduces Adipocyte Differentiation. The Journal of Inherited Metabolic Disease (JIMD). ISSN 0141-8955. 36, p. S44–S44. doi: 10.1007/s10545-013-9631-1. Full text in Research Archive
• Azqueta, Oscoz Amaya; Costa, Solange; Lorenzo, Yolanda Corrales; Bastani, Nasser Ezzatkhah & Collins, Andrew Richard (2013). Vitamin C in Cultured Human (HeLa) Cells: Lack of Effect on DNA Protection and Repair. Nutrients. 5(4), p. 1200–1217. doi: 10.3390/nu5041200. Full text in Research Archive
• Bastani, Nasser Ezzatkhah; Gundersen, Thomas Erik & Blomhoff, Rune (2012). Dried blood spot (DBS) sample collection for determination of the oxidative stress biomarker 8-epi-PGF2a in humans using liquid chromatography/tandem mass spectrometry. Rapid Communications in Mass Spectrometry. ISSN 0951-4198. 26(6), p. 645–652. doi: 10.1002/rcm.6149. Full text in Research Archive
• Bilbija, Dusan; Haugen, Fred; Sagave, Julia Fritzi; Baysa, Anton; Bastani, Nasser Ezzatkhah & Levy, Finn Olav [Show all 9 contributors for this article] (2012). Retinoic Acid Signalling Is Activated in the Postischemic Heart and May Influence Remodelling. PLOS ONE. 7(9). doi: 10.1371/journal.pone.0044740. Full text in Research Archive
• Bastani, Nasser Ezzatkhah; Kostovski, Emil; Sakhi, Amrit Kaur; Karlsen, Anette; Carlsen, Monica Hauger & Hjeltnes, Nils [Show all 8 contributors for this article] (2012). Reduced Antioxidant Defense and Increased Oxidative Stress in Spinal Cord Injured Patients. Archives of Physical Medicine and Rehabilitation. ISSN 0003-9993. 93(12), p. 2223–2228. doi: 10.1016/j.apmr.2012.06.021. Full text in Research Archive
• Karlsen, Anette; Svendsen, Mette; Seljeflot, Ingebjørg; Sommernes, Mary-Ann; Sexton, Joseph & Brevik, Asgeir [Show all 23 contributors for this article] (2011). Compliance, tolerability and safety of two antioxidant-rich diets: a randomised controlled trial in male smokers. British Journal of Nutrition. ISSN 0007-1145. 106(4), p. 557–571. doi: 10.1017/S0007114511000353. Full text in Research Archive
• Bastani, Nasser Ezzatkhah; Gundersen, Thomas Erik & Blomhoff, Rune (2009). Determination of 8-epi PGF(2 alpha) concentrations as a biomarker of oxidative stress using triple-stage liquid chromatography/tandem mass spectrometry. Rapid Communications in Mass Spectrometry. ISSN 0951-4198. 23(18), p. 2885–2890. doi: 10.1002/rcm.4197. Full text in Research Archive
• Sakhi, Amrit Kaur; Russnes, Kjell Magne; Thoresen, Magne; Bastani, Nasser Ezzatkhah; Karlsen, Anette & Smeland, Sigbjørn [Show all 7 contributors for this article] (2009). Pre-radiotherapy plasma carotenoids and markers of oxidative stress are associated with survival in head and neck squamous cell carcinoma patients: a prospective study. BMC Cancer. 9(1), p. 458–458. Full text in Research Archive
• Gundersen, Thomas Erik; Bastani, Nasser Ezzatkhah & Blomhoff, Rune (2007). Quantitative high-throughput determination of endogenous retinoids in human plasma using triple-stage liquid chromatography/tandem mass spectrometry. Rapid Communications in Mass Spectrometry. ISSN 0951-4198. 21. doi: 10.1002/rcm.2946. Full text in Research Archive

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• Clauss, Matthieu; Puissant, Clair; Bastani, Nasser Ezzatkhah; Nielsen, Lotte L. K.; Skålhegg, Bjørn Steen & Jeppesen, Per Bendix [Show all 7 contributors for this article] (2025). Effect of high intakes of protein-only and carbohydrate-only on plasma metabolites and hormones, in addition to nitrogen excretion. doi: 10.1007/978-1-0716-4414-0_16. Full text in Research Archive
• Rundblad, Amanda; Christensen, Jacob Juel; Hustad, Kristin Solheim; Bastani, Nasser Ezzatkhah; Holven, Kirsten Bjørklund & Ulven, Stine Marie (2023). Associations between dietary intake and glucose tolerance in  clinical and metabolomics-based metabotypes. Full text in Research Archive
• Elshorbagy, Amany; Bastani, Nasser Ezzatkhah; Lee-Ødegård, Sindre; Øvrebø, Bente; Yasein, Nadia Haj & Svendsen, Karianne [Show all 10 contributors for this article] (2023). Correction to: The association of fasting plasma thiol fractions with body fat compartments, biomarker profile, and adipose tissue gene expression (Amino Acids, (2022), 10.1007/s00726-022-03229-2). Amino Acids. ISSN 0939-4451. 55, p. 547–548. doi: 10.1007/s00726-023-03244-x. Full text in Research Archive
• Stålberg, Stina Margrethe; Silwat-Pandit, Laxmi; Bastani, Nasser Ezzatkhah; Nebdal, Daniel JH; Skålhegg, Bjørn Steen & Kure, Elin Wenche Hegland (2023). Metabolite profiles in plasma distinguish between patients with periampullary cancer and benign pancreatic disease. Full text in Research Archive
• Bastani, Nasser Ezzatkhah; Refsum, Helga; Olsen, Thomas; Vinknes, Kathrine Jørgensen; Retterstøl, Kjetil & Zare, Hasse Khiabani (2022). Determination of plasma thiols using LC-MS/MS: Cysteine-lowering treatment with mesna against obesity: Preliminary results from a phase I dose-finding stud. Full text in Research Archive
• Rangel-Huerta, Oscar Daniel; Paur, Ingvild; Bastani, Nasser Ezzatkhah; Bøhn, Siv Kjølsrud; Lilleby, Wolfgang & Smeland, Sigbjørn [Show all 8 contributors for this article] (2017). Association between amino acids, biomarkers of prostate cancer and inflammation in Norwegian prostate cancer patients. Full text in Research Archive
• Bastani, Nasser Ezzatkhah & Sakhi, Amrit Kaur (2014). Self-sampled dried blood spot and saliva samples collected at home and shipped by the postal service in a population-based study. Full text in Research Archive Show summary

  A common challenge for large epidemiological studies is obtaining and transporting biological samples. This challenge is especially true for blood samples. Trained personnel are required to take blood samples, and thus participants either need to visit doctor´s offices or study personnel need to visit the participants. Furthermore, blood samples typically must be shipped directly from the medical center to the receiving laboratory. To overcome some of these challenges it has been suggested that participants could self-sample dried blood spots (DBS) for serum markers and saliva samples for DNA and ship such specimens by postal service directly to the laboratory. DBSs can be obtained by a simple finger-prick test that yields blood drops, which are collected on sampling paper. However, the expected response rate for this kind of sample collection is not known in large epidemiological studies. Specifically, it is not clear whether participants would be reluctant to take their own blood samples. It is also not known whether participants would be able to understand written instructions for obtaining and shipment of the blood sample adequately. Further, to what extent participants would contact study personnel with questions about the DBS protocol, is unknown.

• Sakhi, Amrit Kaur; Bøhn, Siv Kjølsrud; Kvendbø, Eva; Helle, Christine; Garthe, Ina & Erlund, Iris [Show all 12 contributors for this article] (2009). Effect of blueberry and red grape juice on plasma antioxidants, inflammation, oxidative- and muscle damage biomarkers in elite athletes practicing endurance training. Full text in Research Archive Show summary

  Background and aim: Intensive exercise of long duration increases blood levels of oxidative damage- and inflammatory biomarkers. Different polyphenols in blueberries and red grapes have antioxidant properties and prevent oxidative damage, thereby, contributing in prevention of different oxidative stress related diseases like cancer, stroke, cardiovascular diseases, neurodegenerative diseases and diabetes. The aim of our study was to study the effect of polyphenol-rich juice on the plasma antioxidants, inflammation, oxidative- and muscle damage- biomarkers in elite athletes practicing endurance exercise. Methods: The study is randomized, double-blind and followed a parallel design with 5-8 week intervention period. Norwegian male athletes competing in endurance sports at national team levels exercising 15 hours or more per week were recruited through Olympiatoppen. After washout period of one week, the participants were invited to give fasting blood samples and anthropometric measurements. The juice group consumed two boxes of European blueberry/red grape juices (2 x 330 mL) every day in the intervention period. The placebo group received a placebo drink (2 x 330 mL) every day with similar carbohydrate and energy amount as the juice. The participants registered their physical exercise every day during the intervention period. We have measured 35 different plasma/erythrocyte antioxidants including 12 different polyphenols, plasma total antioxidant capacity, 5 different plasma/erythrocyte oxidative damage biomarkers, marker for muscle damage, 23 different inflammatory markers in fasting blood samples taken before and after 5-8 weeks of intervention. Results: Among the antioxidants measured, polyphenols increased significantly in the juice group (p<0.05). The muscle damage biomarker creatine kinase decreased significantly in the juice group (p=0.055) and most of the inflammation biomarkers decreased in the juice group. Conclusion: The results indicate that the blueberry and red grape juice increases the concentration of different polyphenols in the plasma and may reduce muscle damage and inflammation in elite athletes. Supported by: The Norwegian Cancer Society, The Research Council of Norway, Throne Holst Foundation and Tine BA.

• Bøhn, Siv Kjølsrud; Myhrstad, Mari Charlotte; Thoresen, Magne; Marciuch, Anne; Vasstrand, Ann kristin & Carlsen, Monica Hauger [Show all 13 contributors for this article] (2009). Effect of berry and grape polyphenols on cognition and blood parameters in normal, aged men with subjective memory decline. Full text in Research Archive

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