Prevention of Type 2 Diabetes through Sardines Consumption: An Integrative Review

Figures & data

Figure 1. Justification for the choice of sardines in relation to possible preventive effects in humans against the risk of developing T2D.

Table 1. Studies with taurine supplementation.

Compound	Dose	Model	Sample size	Effect	Reference
Taurine	0,3 mM taurine	3T3-L1 preadipocyte In vitro	-	Promotion of autophagosome formation and autophagic flux. Antioxidant activity through ROS.	^[Citation100]
Taurine	1% taurine per day 21 days	Adult male Wistar rats	45 total. Taurine groups: 6 non-diabetic and 10 diabetic	Restores GLUT4 expression. Antioxidant, antihyperlipidemic and antiinflammatory action. Decreases circulating damage cardiac markers, proinflammatory cytokines and NFkB translocation.	^[Citation101]
Taurine	2% taurine 30 days	Male Swiss mice	76 total. 36 in group of taurine supplemented	Higher nuclear expression of PDX-1 and peripheral insulin sensitivity. No effect on body weight nor basal blood glucose.	^[Citation92]
Taurine	5% taurine supplement 19 weeks	Female and male Swiss mice	Total not reported. 7–30 in each 2 groups of taurine supplemented	Improves plasma glucose levels (117 ± 7 and 142 ± 7 mg/dL taurine supplemented and control respectively), glucose tolerance (ipGTT around −100 mg/dL at 120 and 180 min compared to control), insulin sensitivity (AUC for ipGTT around −1000 mg/dL.min^−1 compared to control) and activates Akt in liver (30% higher than control) in high fat diet fed ones.	^[Citation95]
Taurine	2% taurine, high fat diet 10 weeks	Male mice C57BL/6	40 total. 8–10 in each 2 groups of taurine supplemented	Improves in high fat diet mice body weight (8.7 ± 0.8 and 14.5 ± 0.9 gr taurine supplemented and control respectively) and visceral fat (1229.8 ± 214.7 and 1866.3 ± 183.5 mg taurine supplemented and control respectively). Improves plasma glucose levels (around −20 mg/dL in all timepoint compared to control) disturbance plasma insulin (between −4 and −10 ng/ml in different timepoint compared to control) and leptin (between −5 and −50 ng/ml in different timepoint compared to control) and Per1 expression in pancreatic islets.	^[Citation102]
Taurine	2% taurine, 12 weeks	OLETF diabetic rats	14 total. 7 in taurine-supplemented group	Ameliorates hyperglycemia (200 mg/dL and >300 mg/dL fasted glucose taurine supplemented and control respectively) and dyslipidemia by reducing insulin resistance (HOMA-IR was half in the group supplemented with taurine) and leptin level (serum leptin levels was half in the group supplemented with taurine)	^[Citation103]
Taurine	750 mg/kg taurine 71 days	Alloxan-treated diabetic rats	75 total. 25 in taurine-supplemented group	Improves hyperglycemia by glucose plasma reduction (3.69 ± 0.12 and 10.34 ± 0.92 mmol/L taurine supplemented and control respectively) and insulin plasma increase (56.03 ± 2.78 and 21.23 ± 0.74 pmol/L taurine supplemented and control respectively)	^[Citation97]
Taurine	1,5 g/day 8 weeks	Overweight men with a genetic predisposition for T2D	20 total. 10 in taurine-supplemented group	No effect of taurine on body weight, blood pressure, insulin secretion and sensitivity nor glucose homeostasis and HbA1c.	^[Citation98]
Taurine	3 g/day 4 months	T2D participants without DM-medication	45 total. 30 in taurine-supplemented group	No effects in glucose, HbA1c, lipids or insulin.	^[Citation99]

Table 2. Studies with taurine and omega-3/oily fish supplementation.

Compound	Dose	Model	Sample size	Effect	Reference
Soybean or fish oil ± taurine	Soybean, soybean + taurine, fish oil, fish oil + taurine 4 weeks	Type 2 Diabetic/Obese KK-Ay Mice	36 total. 6–7 in each 3 groups of fish oil + taurine supplemented	Taurine supplemented fish oil, compared to supplemented soybean oil, decreases blood glucose (around −200 mg/dL) and insulin (around −0.5 ng/mL).	^[Citation112]
Omega-3 + taurine	1 g/day EPA/DHA + 425 mg/d taurine 7 weeks	Healthy adult human	80 total. 41 in group of omega-3 + taurine supplemented	Decrease of total cholesterol (−5%), LDL cholesterol (−8%) and Apo B (−4%) and increase HDL cholesterol (6%).	^[Citation111]

Table 3. Sardines composition by United States Department of Agriculture (USDA) .^[113].

Nutrient	Unit	Value	Nutrient	Unit	Value
		(per 100 g)			(per 100 g)
Water	g	59.61	Vitamins
Energy	kcal	208	Vitamin C, total ascorbic acid	mg	0.00
Energy	kJ	871	Thiamin	mg	0.08
Protein	g	24.62	Riboflavin	mg	0.23
Total lipid (fat)	g	11.45	Niacin	mg	5.25
Carbohydrate	g	0.00	Pantothenic acid	mg	0.64
Fiber, total dietary	g	0.00	Vitamin B-6	mg	0.17
Minerals			Folate. total	µg	10
Calcium, Ca	mg	382	Folic acid	µg	0
Iron, Fe	mg	2.92	Choline, total	mg	75
Magnesium, Mg	mg	39	Vitamin B-12	µg	8.94
Phosphorus, P	mg	490	Vitamin A, RAE	µg	32
Potassium, K	mg	397	Retinol	µg	32
Sodium, Na	mg	307	Vitamin A, IU	IU	108
Zinc, Zn	mg	1.31	Vitamin D (D2 + D3)	µg	4.80
Copper, Cu	mg	0.19	Vitamin D	IU	193
Manganese, Mn	mg	0.11	Vitamin E	mg	2.04
Selenium, Se	µg	52.70	Vitamin K	µg	2.60
Nutrient	Unit	Value	Nutrient	Unit	Value
		(per 100 g)			(per 100 g)
Fatty acids			Fatty acids
Fatty acids, total saturated	g	1.53	Fatty acids. total polyunsaturated	g	5.15
12:0	g	0.00	18:2 undifferentiated	g	3.54
14:0	g	0.19	18:3 undifferentiated	g	0.50
16:0	g	0.99	18:4	g	0.13
18:0	g	0.34	20:4 undifferentiated	g	0.00
Fatty acids. total monounsaturated	g	3.87	20:5 n-3 (EPA)	g	0.47
16:1 undifferentiated	g	0.22	22:5 n-3 (DPA)	g	0.00
18:1 undifferentiated	g	2.15	22:6 n-3 (DHA)	g	0.51
20:1	g	0.42	Cholesterol	mg	149
22:1 undifferentiated	g	1.08
Nutrient	Unit	Value	Nutrient	Unit	Value
		(per 100 g)			(per 100g)
Amino acids			Amino acids
Tryptophan	g	0.28	Valine	g	1.27
Threonine	g	1.08	Arginine	g	1.47
Isoleucine	g	1.13	Histidine	g	0.73
Leucine	g	2	Alanine	g	1.49
Lysine	g	2.26	Aspartic acid	g	2.52
Methionine	g	0.73	Glutamic acid	g	3.67
Cystine	g	0.27	Glycine	g	1.81
Phenylalanine	g	0.96	Proline	g	0.87
Tyrosine	g	0.83	Serine	g	1

Table 4. Studies with sardine supplementation.

Compound	Dose	Model	Sample size	Effect	Reference
Sardine by-products	30% 30 days	Wistar rats (In vivo)	12 total. 6 in group of sardine by-products supplemented	Reduction of glycemia (7.23 ± 0.28 and 8.93 ± 0.75 mmol/L sardine supplemented and control respectively) and HbA1c (3.14 ± 0.70 and 5.51 ± 1.51% sardine supplemented and control respectively). Moreover, reduction of SBP, DBP, TAG, total cholesterol, LDL cholesterol and VLDL. Increase of HDL cholesterol and LCAT enzyme.	^[Citation120]
Canned sardines	11% or 22% of the total diet. 10 weeks	Wistar rats (In vivo)	27 total. 9 in each 2 groups of canned sardines supplemented	22% of sardines group had higher % of EPA+DHA and MUFA. Increase omega-3 FA:omega-6 FA ratio. Higher EPA deposition in liver and erythrocytes. Decrease total cholesterol decrease LDL cholesteroland increase adiponectin in both groups (21.8–24.5 and 18.7 µg/ml sardine and control group respectively).	^[Citation121]
Sardine	100g sardine 5d/week. 6 months	T2D subjects without antidiabetic drugs	35 total. 19 in group of sardine supplemented	Increased adiponectin (40.7%), omega-3 FA index (2.6%) and Prevotella concentrations. Decreased Firmicutes/Bacteroidetes ratio	^[Citation122]
Sardine canned sandwich	3 times per week. 8 weeks.	Human subjects receiving hemodialysis	63 total. 31 in group of sardine sandwich supplemented	Reduction of CRP in patients with higher baseline concentrations (−1.01 ± 1.11 and −0.079 ± 0.85 the higher and lower CRP at baseline respectively).	^[Citation123]

Table 5. Studies with sardine oil supplementation.

Compound	Dose	Model	Sample size	Effect	Reference
Sardine oil	20% 30 days or 60 days	Male Wistar rats (In vivo)	24 total. 12 in group of sardine oil supplemented. And 6 from control group started with sardine oil at middle of study.	Lowers hypertriglyceridemia (−68%) and hypercholesterolemia (−50%) replacing margarine. No effects on glycemia but improves HbA1c (−36%) and insulinemia (−65%) when sardine oil replaces margarine.	^[Citation125]
Sardine oil	20% 4 weeks	Obese male Wistar rats (in vivo)	16 total. 8 in group of sardine oil supplemented	No effect on glycemia. Reduces cholesterol (−8%), TAG (−36%) and apolipoproteins. Increased lecithin (35%) and paraoxonase-1 activity (25%).	^[Citation89]
Sardine oil	0,5 mL/rat 3 weeks	Alloxan-induced diabetic rats	32 total. 8 in group of sardine oil supplemented	Decreases glycemia (−54%). Inhibition of α-amylase activity (−27%). Improve ALT, AST and ALP enzymes (−66, 26 and 69% respectively).	^[Citation126]
Sardine oil	7,5% 6 weeks	Sucrose-induced metabolic syndrome male Wistar rats.	44 total. 10 in group of sardine oil supplemented	Serum glucose remained similar to no metabolic syndrome rats. Moreover, other metabolic parameters returns to control level (reduces serum insulin by −150%, BP by −60%,, TAG by −98%, total cholesterol by −106% and LDL cholesterol by −40%)	^[Citation127]
Sardine oil	Oil capsules: 180 mg EPA and 120 mg DHA during 90 days	Human with metabolic syndrome.	102 in total. 21 in group of sardine oil supplemented and 26 in group with control supplementation + sardine oil.	Reduction of prooxidant state (hydroperoxide, AOPP, AOPP/TRAP index and TRAP/AOPP index). No effects on glycemia, insulin levels or HOMA-IR. Decreases total cholesterol (around −20 mg/dL compared to control) and LDL cholesterol (around −27 mg/dL post-intervention).	^[Citation128]

Table 6. Studies of sardine protein supplementation.

Compound	Dose	Model	Sample size	Effect	Reference
Sardine protein	200 g/kg 2 months	Wistar rats (in vivo)	24 in total. 6 in each 2 groups sardine-protein supplemented.	Decrease of glycemia and insulin levels (glucose 6.54 ± 0.47 and 8.31 ± 1.06 mmol/l, insulin 43.22 ± 12.25 and 66.65 ± 5.97 µU/ml sardine protein supplemented and control in high-fructose diets respectively). Likewise, in same diet, reduces HOMA-IR (12.70 ± 4.46 and 21.94 ± 5.43) and HbA1c (10.39 ± 1.29 and 16.42 ± 1.74%) sardine protein supplemented and control respectively. Reduces index of adiposity (2.05 ± 0.29 and 2.68 ± 0.14) and TAG (0.92 ± 0.09 and 1.21 ± 0.08) sardine protein supplemented and control respectively. Decrease inflammatory markers (leptin between −15 and −19% and TNF-α between −16 and −31%).	^[Citation124]
Sardine protein	20% 28 days	High-fat diet-induced T2D rats.	24 in total. 6 in each 2 groups of sardine-protein supplemented	Lowers glycemia (14.49 ± 2.07 and 23.15 ± 1.71 mM), HbA1c (8.32 ± 0.84 and 11.70 ± 1.51%) and insulin levels (292.10 ± 21.91 and 331.77 ± 24.89 pmol/l) likewise HOMA-IR (24.90 ± 1.50 and 50.54 ± 4.14) sardine protein supplemented and control respectively. Reduce serum total cholesterol (2.51 ± 0.44 and 4.71 ± 0.73 mM) and TAG (1.97 ± 0.58 and 3.51 ± 0.43 mM) sardine protein supplemented and control respectively. Enhances LCAT activity (16.74 ± 5.81 and 27.55 ± 2.09 nol/h per ml).	^[Citation129]

Kaneko, H.; Kobayashi, M.; Mizunoe, Y.; Yoshida, M.; Yasukawa, H.; Hoshino, S.; Itagawa, R.; Furuichi, T.; Okita, N.; Sudo, Y.; et al. Taurine Is an Amino Acid with the Ability to Activate Autophagy in Adipocytes. Amino Acids. 2018, 50(5), 527–535.

 PubMed Web of Science ®Google Scholar

Das, J.; Vasan, V.; Sil, P. C. Taurine Exerts Hypoglycemic Effect in Alloxan-induced Diabetic Rats, Improves Insulin-mediated Glucose Transport Signaling Pathway in Heart and Ameliorates Cardiac Oxidative Stress and Apoptosis. Toxicol. Appl. Pharmacol. 2012, 258(2), 296–308. DOI: 10.1016/j.taap.2011.11.009.

 PubMed Web of Science ®Google Scholar

Carneiro, E. M.; Latorraca, M. Q.; Araujo, E.; Beltrá, M.; Oliveras, M. J.; Navarro, M.; Berná, G.; Bedoya, F. J.; Velloso, A.; Soria, B.; et al. Taurine Supplementation Modulates Glucose Homeostasis and Islet Function. J. Nutr. Biochem. 2009, 20(7), 503–511.

 PubMed Web of Science ®Google Scholar

Ribeiro, R. A.; Santos-Silv, J. C.; Vettorazzi, J. F.; Cotrim, B. B.; Mobiolli, D. D. M.; Boschero, A. C.; CArneiro, E. M. Taurine Supplementation Prevents Morpho-physiological Alterations in High- Fat Diet Mice Pancreatic B-cells. Amino Acids. 2012, 43(4), 1791–1801. DOI: 10.1007/s00726-012-1263-5.

 PubMed Web of Science ®Google Scholar

Figueroa, A. L.; Figueiredo, H.; Rebuffat, S.; Vieira, E.; Gomis, R. Taurine Treatment Modulates Circadian Rhythms in Mice Fed A High Fat Diet. Sci. Rep. 2016, 6(November), 1–13. DOI: 10.1038/srep36801.

 PubMedGoogle Scholar

Kim, K. S.; Oh, D. H.; Kim, J. Y.; Lee, B. G.; You, J. S.; Chang, K. J.; Chung, H. J.; Yoo, M. C.; Yang, H. I.; Kang, J. H.; et al. Taurine Ameliorates Hyperglycemia and Dyslipidemia by Reducing Insulin Resistance and Leptin Level in Otsuka Long-Evans Tokushima Fatty (OLETF) Rats with Long-term Diabetes. Exp. Mol. Med. 2012, 44(11), 665–673.

 PubMed Web of Science ®Google Scholar

Gavrovskaya, L. K.; Ryzhova, O. V.; Safonova, A. F.; Matveev, A. K.; Sapronov, N. S. Protective Effect of Taurine on Rats with Experimental Insulin-dependent Diabetes Mellitus. Bull. Exp. Biol. Med. 2008, 146(2), 226–228. DOI: 10.1007/s10517-008-0258-4.

 PubMed Web of Science ®Google Scholar

Brøns, C.; Spohr, C.; Storgaard, H.; Dyerberg, J.; Vaag, A. Effect of Taurine Treatment on Insulin Secretion and Action, and on Serum Lipid Levels in Overweight Men with a Genetic Predisposition for Type II Diabetes Mellitus. Eur. J. Clin. Nutr. 2004, 58(9), 1239–1247. DOI: 10.1038/sj.ejcn.1601955.

 PubMed Web of Science ®Google Scholar

Chauncey, K. B.; Tenner, T. E.; Lombardini, J. B.; Jones, B. G.; Brooks, M. L.; Warner, R. D.; David, R. L.; Ragain, R. M. The Effect of Taurine Supplementation on Patients with Type 2 Diabetes Mellitus. Taur. 5. Adv. Exp. Med. Biol. 2003, 526, 91–96.

 PubMed Web of Science ®Google Scholar

Mikami, N.; Hosokawa, M.; Miyashita, K. Dietary Combination of Fish Oil and Taurine Decreases Fat Accumulation and Ameliorates Blood Glucose Levels in Type 2 Diabetic/Obese KK-A Y Mice. J. Food Sci. 2012, 77(6), 114–120. DOI: 10.1111/j.1750-3841.2012.02687.x.

 Web of Science ®Google Scholar

Elvevoll, E. O.; Eilertsen, K. E.; Brox, J.; Dragnes, B. T.; Falkenberg, P.; Olsen, J. O.; Kirkhus, B.; Lamglait, A.; Osternud, B. Seafood Diets: Hypolipidemic and Antiatherogenic Effects of Taurine and N-3 Fatty Acids. Atherosclerosis. 2008, 200(2), 396–402. DOI: 10.1016/j.atherosclerosis.2007.12.021.

 PubMed Web of Science ®Google Scholar

United States Department of Agriculture. Agricultural Research Service; National Nutrient Database for Standard Reference Legacy Release. https://www.usda.gov/(accessed July 24, 2019).

 Google Scholar

Affane, F.; Benahmed Daidj, N. B.; Louala, S.; Munezero, A. N.; Lamri-Senhadji, M. Y. Effects of an Obesogenic Diet Enriched in Sardine By-products on Pro-atherogenic Markers in Wistar Rats. Ann. Cardiol. Angeiol. 2016, 65(3), 214–218. DOI: 10.1016/j.ancard.2016.04.011.

 PubMedGoogle Scholar

Rodrigues, P. O.; Martins, S. V.; Lopes, P. A.; Ramos, C.; Miguéis, S.; Alfaia, C. M.; Pinto, R. M.; Rolo, E. A.; Bispo, P.; Batista, I.; et al. Influence of Feeding Graded Levels of Canned Sardines on the Inflammatory Markers and Tissue Fatty Acid Composition of Wistar Rats. Br. J. Nutr. 2014, 112(3), 309–319.

 PubMed Web of Science ®Google Scholar

Balfegò, M.; Canivell, S.; Hanzu, F. A.; Sala-Vila, A.; Martínez-Medina, M.; Murillo, S.; Mur, T.; Ruano, E.; Linares, F.; Porras, N.; et al. Effects of Sardine-enriched Diet on Metabolic Control, Inflammation and Gut Microbiota in Drug-naïve Patients with Type 2 Diabetes: A Pilot Randomized. Lipids Health Dis. 2016, 15(1), DOI: 10.1186/s12944-016-0245-0.

 PubMedGoogle Scholar

Moreira, A. C.; Gaspar, A.; Serra, M. A.; Simões, J.; Lopes da Cruz, J.; Amaral, T. F. Effect of a Sardine Supplement on C-reactive Protein in Patients Receiving Hemodialysis. J. Ren. Nutr. 2007, 17(3), 205–213. DOI: 10.1053/j.jrn.2007.02.005.

 PubMed Web of Science ®Google Scholar

Hamza-Reguig, S.; Benahmed Daidj, N. B.; Louala, S.; Boualga, A.; Lamri-Senhadji, M. Effect of Replacing Sardine Oil with Margarine on Dyslipidemia, Dysglycemia and Redox Status of Adipose Tissue in High-fat Diet-induced Obesity in Wistar Rats. Nutr. Food Sci. 2017, 47(1), 2–17. DOI: 10.1108/NFS-04-2016-0041.

 Web of Science ®Google Scholar

Boukhari, N.; Taleb-Senouci, D.; Chabane, F. Z.; Besbes, M.; Lamri-Senhadji, M. Y. Fish By-products Oil Corrects Dyslipidemia, Improves Reverse Cholesterol Transport and Stimulates Paraoxonase-1 Activity in Obese Rat. Ann. Cardiol. Angeiol. (Paris). 2013, 62(3), 149–154. DOI: 10.1016/j.ancard.2013.04.007.

 PubMedGoogle Scholar

BelHadj, S.; Hentati, O.; Baccouch, N.; Ben Salah, H.; Boudaouara, T.; Ben Hadj, A.; Allouch, N.; El Feki, A. F. Effect of Sardina Pilchardus Oil on Alloxan-induced Diabetic Rats. J. Metab. Dis. 2016, 122(1), 27–35.

 Google Scholar

Aguilera, A. A.; Díaz, G. H.; Barcelata, M. L.; Guerrero, O. A.; Ros, R. M. Effects of Fish Oil on Hypertension, Plasma Lipids, and Tumor Necrosis factor-α in Rats with Sucrose-induced Metabolic Syndrome. J. Nutr. Biochem. 2004, 15(6), 350–357. DOI: 10.1016/j.jnutbio.2003.12.008.

 PubMed Web of Science ®Google Scholar

Venturini, D.; Simão, A. N.; Urbano, M. R.; Dichi, I. Effects of Extra Virgin Olive Oil and Fish Oil on Lipid Profile and Oxidative Stress in Patients with Metabolic Syndrome. Nutrition. 2015, 31(6), 834–840. DOI: 10.1016/j.nut.2014.12.016.

 PubMed Web of Science ®Google Scholar

Madani, Z.; Louchami, K.; Sener, A.; Malaisse, W. J.; Ait Yahia, D. Dietary Sardine Protein Lowers Insulin Resistance, Leptin and TNF- α and Beneficially Affects Adipose Tissue Oxidative Stress in Rats with Fructose-induced Metabolic Syndrome. Int. J. Mol. Med. 2012, 29(2), 311–318. DOI: 10.3892/ijmm.2011.836.

 PubMed Web of Science ®Google Scholar

Benaicheta, N.; Labbaci, F. Z.; Bouchenak, M.; Boukortt, F. O. Effect of Sardine Proteins on Hyperglycaemia, Hyperlipidaemia and Lecithin:cholesterol Acyltransferase Activity, in High-fat Diet-induced Type 2 Diabetic Rats. Br. J. Nutr. 2016, 115(1), 6–13. DOI: 10.1017/S0007114515004195.

 PubMed Web of Science ®Google Scholar