Effects of n−3 fatty acids in subjects with type 2 diabetes: reduction of insulin sensitivity and time-dependent alteration from carbohydrate to fat oxidation
Open accessAbstract
Background Effects of fish oil supplements on metabolic variables are insufficiently clarified in type 2 diabetes.Objective We aimed to investigate short-term (1 wk) and longer-term (9 wk) effects of n-3 fatty acids.Design Twenty-six subjects with type 2 diabetes without hypertriacylglycerolemia participated in a double-blind controlled study. Median intake in the intervention group was 17.6 mL fish oil/d (1.8 g 20:5n-3, 3.0 g 22:6n-3, and 5.9 g total n-3 fatty acids). The control group received 17.8 mL corn oil/d (8.5 g 18:2n-6).Results Plasma phospholipid 20:5n-3 and 22:6n-3 increased, whereas 18:2n-6 decreased, in the fish oil group compared with the corn oil group after 1 wk. The two n-3 fatty acids also increased in adipose tissue biopsy samples taken after 9 wk in the fish oil group. Glucose concentrations (home-monitored) were approximately 1 mmol/L higher in the fish oil group than in the corn oil group at the end of the intervention (P = 0.035). Glucose utilization measured by using an isoglycemic clamp was lowered in the fish oil group compared with that in the corn oil group at the end of the intervention (P = 0.049), whereas glucagon-stimulated C-peptide tended to increase (P = 0.078). The fish oil group utilized less fat for oxidation after 1 wk, with a change to more fat and less carbohydrate oxidation after 9 wk (P = 0.040), than did the corn oil group.Conclusion A high intake of fish oil moderately increases blood glucose and decreases insulin sensitivity in persons with type 2 diabetes without hypertriacylglycerolemia and alters carbohydrate and fat utilization in a time-dependent manner.
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Increased hepatic fatty acid oxidation is likely the mechanism for reduced VLDL production.
“rather, increased hepatic fatty acid oxidation is likely.”
OM3FA treatment increases fatty acid oxidation.
“Clinical studies have shown that OM3FA treatment increases fatty acid oxidation, as determined by indirect calorimetry [35, 36].”
Mostad and colleagues observed that the short term response to intake of omega-3 PUFAs was a decrease in fat oxidation, but the opposite effect was observed after nine weeks.
“Mostad and colleagues (2006) observed that the short term response to intake of omega-3 PUFAs was a decrease in fat oxidation but the opposite effect was observed after nine weeks [92].”
From Omega-3 Fatty Acids and Skeletal Muscle Health (2015) · cites this paper as [92]
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BackgroundResultDietary omega-3 fatty acids and fish consumption and risk of type 2 diabetes
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“0 g DHA) in people with diabetes had negative effects on insulin sensitivity, as assessed by isoglycemic clamp, compared to corn oil–fed controls [4].”
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“Studies measuring the change in adipose tissue fatty acid composition, as a marker of compliance to n-3 supplementation are limited and findings inconsistent with some [29–32] but not all [33,34] noting small but significant increases in the abundance of adipose tissue EPA and DHA after varying periods of fish oil sup…”
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Omega-3 supplementation and diabetes: A systematic review and meta-analysis
Delpino, F. M., Figueiredo, L. M., da Silva, B. G. C., da Silva, T. G., Mintem, G. C., Bielemann, R. M., & Gigante, D. P. (2021) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1875977 · Cited by 79 · see citing works
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“Some studies indicate that n-3 PUFAs improve insulin sensitivity in humans (17–21), whereas others find that n-3 PUFAs have no insulin-sensitizing effects (22–25) or may even worsen long-term glycemic control (26).”
BackgroundNutritional Management of Insulin Resistance in Nonalcoholic Fatty Liver Disease (NAFLD)
Conlon, B. A., Beasley, J. M., Aebersold, K., Jhangiani, S. S., & Wylie‐Rosett, J. (2013) · Nutrients · doi:10.3390/nu5104093 · Cited by 73 · see citing works
“n-3 PUFA supplements have been associated with increases in fasting plasma glucose, but they are also associated with reductions in HbA1c and CVD risk factors [9,80,81].”
BackgroundThe effect of alpha-linolenic acid on glycemic control in individuals with type 2 diabetes
Jovanovski, E., Li, D., Ho, H. V. T., Djedovic, V., Marques, A. D. C. R., Shishtar, E., Mejía, S. B., Sievenpiper, J. L., de Souza, R. J., Duvnjak, L. S., et al. (2017) · Medicine · doi:10.1097/md.0000000000006531 · Cited by 75 · see citing works
“[5] Evidence from randomized controlled trials (RCTs) suggests that fish omega-3 PUFAs, eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA), do not improve glycemic parameters in T2DM.”
BackgroundInfluentialN-3 fatty acids in glucose metabolism and insulin sensitivity.
Olalla, L. M. D. S., Sánchez-Muniz, F. J., & Vaquero, M. P. (2009) · PubMed · Cited by 71 · see citing works
Obesity and diabetes: lipids, ‘nowhere to run to'
Hill, M. J., Metcalfe, D., & McTernan, P. G. (2008) · Clinical Science · doi:10.1042/cs20080050 · Cited by 66 · see citing works
Chacińska, M., Zabielski, P., Książek, M., Szałaj, P., Jarząbek, K., Kojta, I., Chabowski, A., & Błachnio-Zabielska, A. U. (2019) · Nutrients · doi:10.3390/nu11040835 · Cited by 64 · see citing works
“Despite the fact that there is evidence that OMEGA-3 is beneficial, there are still some studies that speak about the unfavorable effect of PUFAs [11,12], especially when OMEGA-3 were used as the primary source of PUFAs to treat patients with type 2 diabetes [13].”
BackgroundChu, X., Liu, L., Na, L., Lu, H., Li, S., Li, Y., & Sun, C. (2012) · Diabetes · doi:10.2337/db12-0139 · Cited by 58 · see citing works
Effects of Fish Oil Supplementation on Markers of the Metabolic Syndrome
Pedersen, M. H., Mølgaard, C., Hellgren, L. I., & Lauritzen, L. (2010) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2010.04.001 · Cited by 58 · see citing works
Polyunsaturated fatty acids and cardiovascular disease
Richard, D., Bausero, P., Schneider, C., & Visioli, F. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0085-4 · Cited by 57 · see citing works
Functional foods for health: Focus on diabetes
Rudkowska, I. (2009) · Maturitas · doi:10.1016/j.maturitas.2009.01.011 · Cited by 58 · see citing works
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Abbott, K. A., Burrows, T. L., Thota, R. N., Acharya, S., & Garg, M. L. (2016) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.116.138172 · Cited by 56 · see citing works
Mostad, I. L., Bjerve, K. S., Lydersen, S., & Grill, V. (2007) · European Journal of Clinical Nutrition · doi:10.1038/sj.ejcn.1602703 · Cited by 55 · see citing works
“Results were computed with regard to intake of energy and nutrients, as described (Mostad et al., 2006).”
BackgroundMethodInfluentialSelf-citationTurunen, A. W., Jula, A., Suominen, A. L., Männistö, S., Marniemi, J., Kiviranta, H., Tiittanen, P., Karanko, H., Moilanen, L., Nieminen, M. S., et al. (2012) · Environmental Research · doi:10.1016/j.envres.2012.09.007 · Cited by 52 · see citing works
“For example, among diabetics, both a decrease (Mostad et al., 2006) and an increase (Karlstrom et al., 2011) in insulin sensitivity have been observed.”
BackgroundFish oil supplementation for two generations increases insulin sensitivity in rats
Hirabara, S. M., Folador, A., Fiamoncini, J., Lambertucci, R. H., Rodrigues, C., Rocha, M. S., Aikawa, J., Yamazaki, R. K., Martins, A. R., Rodrigues, A. C., et al. (2012) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2012.08.014 · Cited by 51 · see citing works
“However, in some studies, n-3 PUFA had no effect or even impaired insulin sensitivity and/or cardiovascular risk factors in obese Zucker rats [41], diet-induced obese humans [42] and diabetic patients [37,43,44].”
BackgroundResultOmega-3 Fatty Acids in Cardiovascular Disease and Diabetes: a Review of Recent Evidence
Bhat, S. Z., Sarkar, S., Zaffar, D., Dandona, P., & Kalyani, R. R. (2023) · Current Cardiology Reports · doi:10.1007/s11886-022-01831-0 · Cited by 50 · see citing works
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Sadeghi, A., Djafarian, K., Mohammadi, H., & Shab‐Bidar, S. (2016) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2016.06.025 · Cited by 49 · see citing works
Makhoul, Z., Kristal, A. R., Gulati, R., Luick, B. R., Bersamin, A., Boyer, B. B., & Mohatt, G. V. (2010) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.2009.28820 · Cited by 48 · see citing works
Alhazmi, A. H., Stojanovski, E., McEvoy, M., & Garg, M. L. (2013) · Public Health Nutrition · doi:10.1017/s1368980013001870 · Cited by 48 · see citing works
Fish oil after abdominal aorta aneurysm surgery
Berger, M. M., Tappy, L., Revelly, J. P., Koletzko, B. V., Gepert, J., Corpataux, J. M., Cayeux, M. C., & Chiolero, R. L. (2008) · European Journal of Clinical Nutrition · doi:10.1038/sj.ejcn.1602817 · Cited by 65 · see citing works
“This contrasts with type II diabetic patients in whom decreased insulin sensitivity and time-dependent alterations from carbohydrate to fat oxidation have been observed during FO supplementation (Mostad et al., 2006).”
BackgroundResultMahdavi, A., Bagherniya, M., Mirenayat, M. S., Atkin, S. L., & Sahebkar, A. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-64872-5_13 · Cited by 44 · see citing works
Nigam, A., Frasure‐Smith, N., Lespérance, F., & Julien, P. (2008) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2008.07.008 · Cited by 42 · see citing works
“However, data from human studies are conflicting, with some studies suggesting benefit [9,10], while most showed no effect [11,12] or even deleterious effects on glucose metabolism [13,14].”
BackgroundKarlström, B., Järvi, A., Byberg, L., Berglund, L., & Vessby, B. O. (2011) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.110.006221 · Cited by 42 · see citing works
Nutrients other than carbohydrates: their effects on glucose homeostasis in humans
Heer, M. A., & Egert, S. (2014) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.2533 · Cited by 41 · see citing works
Veleba, J., Kopecký, J., Janovská, P., Kuda, O., Horakova, O., Malínská, H., Kazdová, L., Oliyarnyk, O., Škop, V., Trnovská, J., et al. (2015) · Nutrition & Metabolism · doi:10.1186/s12986-015-0047-9 · Cited by 41 · see citing works
“data since a relatively large volume (20 ml) of crude fish oil containing different lipid fractions besides EPA + DHA was used [38].”
MethodOelrich, B., Dewell, A., & Gardner, C. D. (2011) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2011.06.003 · Cited by 41 · see citing works
“Finally, two studies found a detrimental effect, manifested as an increase in small, dense LDL particle concentration [29,30].”
BackgroundHarden, C. J., Dible, V. A., Russell, J., Garaiová, I., Plummer, S. F., Barker, M. E., & Corfe, B. M. (2013) · Nutrition Research · doi:10.1016/j.nutres.2013.10.004 · Cited by 41 · see citing works
“[13] Mostad IL, Bjerve KS, Bjorgaas MR, Lydersen S, Grill V.”
BackgroundJafari, T., Fallah, A. A., & Azadbakht, L. (2013) · Maturitas · doi:10.1016/j.maturitas.2013.01.008 · Cited by 39 · see citing works
Egert, S., Fobker, M., Andersen, G., Somoza, V., Erbersdobler, H. F., & Wahrburg, U. (2008) · Annals of Nutrition and Metabolism · doi:10.1159/000172980 · Cited by 38 · see citing works
Itsiopoulos, C., Marx, W., Mayr, H. L., Tatucu-Babet, O. A., Dash, S. R., George, E. S., Trakman, G. L., Kelly, J. T., Thomas, C. J., & Brazionis, L. (2018) · Journal of Nutrition & Intermediary Metabolism · doi:10.1016/j.jnim.2018.02.002 · Cited by 37 · see citing works
“inconsistent results, with omega-3 PUFA supplementation found to both decrease [29] and improve [30] insulin sensitivity.”
ResultStephens, F. B., Mendis, B., Shannon, C. E., Cooper, S., Ortori, C. A., Barrett, D. A., Mansell, P., & Tsintzas, K. (2014) · Clinical Science · doi:10.1042/cs20140031 · Cited by 35 · see citing works
Carstens, M. T., Goedecke, J. H., Dugas, L., Evans, J., Kroff, J., Levitt, N. S., & Lambert, E. V. (2013) · Nutrition & Metabolism · doi:10.1186/1743-7075-10-8 · Cited by 34 · see citing works
Rajabi‐Naeeni, M., Dolatian, M., Qorbani, M., & Vaezi, A. A. (2020) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-020-00549-9 · Cited by 28 · see citing works
Mostad, I. L., Bjerve, K. S., Basu, S., Sutton, P., Frayn, K. N., & Grill, V. (2009) · Metabolism · doi:10.1016/j.metabol.2009.06.003 · Cited by 28 · see citing works
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“PUFA n-3 can affect weight loss through different mechanisms, such as increased fat oxidation and energy expenditure (Mostad et al., 2006), induction of apoptosis in adipocytes (Pérez-Matute et al.”
Simão, A. N. C., Lozovoy, M. A. B., & Dichi, I. (2013) · Nutrition · doi:10.1016/j.nut.2013.05.024 · Cited by 26 · see citing works
Alhazmi, A. H., Stojanovski, E., Garg, M. L., & McEvoy, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0097001 · Cited by 26 · see citing works
“It may increase hepatic gluconeogenesis [34] by increasing uptake and oxidation of free fatty acids in the liver [35] and lowering triacylglycerol [36], or it could lower glucose utilization and increase glucagon-stimulated C-peptide [37].”
BackgroundCalder, P. C. (2022) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000845 · Cited by 25 · see citing works
“Studies report that supplemental EPA+DHA increase whole body fat oxidation in healthy community-dwelling older females [19] and in patients with type-2 diabetes [20], as assessed using indirect calorimetry, although a study in healthy young males did not see this effect [21].”
Azizi-Soleiman, F., Jazayeri, S., Eghtesadi, S., Rajab, A., Heidari, I., Vafa, M. R., & Gohari, M. R. (2013) · Europe PMC (PubMed Central) · Cited by 25 · see citing works
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“Another study of 26 patients with type 2 diabetes found that supplementation with fish oil (5.9 g n-3 FA) or corn oil (8.5 g LA) for 9 weeks significantly increased AT levels of EPA and DHA but not LA (127).”
InfluentialNutritional Profiles in a Public Health Perspective: A Critical Review
Foltran, F., Verduci, E., Ghidina, M., Campoy, C., Jany, K.-D., Widhalm, K., Biasucci, G., Vögele, C., HALPERN, G. M., & Gregori, D. (2010) · Journal of International Medical Research · doi:10.1177/147323001003800202 · Cited by 19 · see citing works
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“Our results agree with those of Mostad et al., [25] who could not find better fasting insulin concentrations after omega-3 supplementation.”
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Polyunsaturated Fatty Acids on Cardiovascular Health: Revealing Potentials of Functional Food
Drenjančević, I., Kralik, G., Kralik, Z., Mihalj, M., Stupin, A., Novak, S., & Grčević, M. (2017) · InTech eBooks · doi:10.5772/67033 · Cited by 13 · see citing works
“showed that n‐3 PUFA supplementation in type‐2 diabetic and obese patients did not improve insulin sensitivity, although those patients had improved lipid metabolism [78].”
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“In addition, interventional studies carried out in Eskimos demonstrated that long-term consumption of marine foodstuffs rich in EPA and DHA contributed to the prevention of T2D [24, 25].”
BackgroundMethodInfluentialWang, L., Huang, X., Sun, M., Zheng, T., Zheng, L., Lin, X., Ruan, J., & Lin, F. Y. (2024) · Nutrition and Diabetes · doi:10.1038/s41387-024-00262-w · Cited by 12 · see citing works
- Authors
- Mostad, I. L., Bjerve, K. S., Bjorgaas, M. R., Lydersen, S., & Grill, V.
- Affiliations
- Norwegian University of Science and Technology (NO)
- Corresponding author
- Mostad, Ingrid L
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2006-12
- Volume
- 84
- Issue
- 3
- Pages
- 540-550
- ISSN
- 0002-9165 (ISSN-L)
- OpenAlex
- W2151700012
- Cited by
- 152
- References
- 45
- Citations by year
- 2025: 5 · 2024: 2 · 2023: 5 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 4 · 2018: 2 · 2017: 9 · 2016: 13 · 2015: 6 · 2014: 9 · 2013: 13 · 2012: 11
- FWCI
- 10.27
- Type
- journal article
- Language
- en
- Update notices
- erratum (2007-06-01)
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- EkstraStiftelsen Helse og Rehabilitering (Stiftelsen Dam)
- Novo Nordisk
- Diabetesforbundet
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- omega-3 fatty acids, fish oil supplementation, type 2 diabetes, insulin sensitivity, glucose utilization, substrate oxidation, plasma phospholipids, adipose tissue fatty acids, corn oil, C-peptide, blood glucose
- MeSH terms
- Adult, Aged, Blood Glucose, Diabetes Mellitus, Type 2, Dietary Fats, Unsaturated, Double-Blind Method, Female, Fish Oils, Hemostasis, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Oxidation-Reduction, Oxygen Consumption, Phospholipids, Time Factors, Glucose Clamp Technique, Fatty Acids, Omega-3, Dietary Supplements, Carbohydrate Metabolism
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