Table 1 Characteristics of the studies that were included in this review
Author | Year | Study Title | Participant Rat Strain | Disease | Intervention | Control | Relevant Outcome Measures | Method of Administration | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
Induction method | Phenotype | Dose | Duration | N | Placebo | N | ||||||
Ohnishi A Fau—Branch, Branch Ra Fau—Jackson 14 | 1986 | Chronic caffeine administration exacerbates renovascular, but not genetic, hypertension in rats | Spontaneously hypertensive rats Okamoto–Aoki strain | Genetic | Hypertension | 0.1% | 7 weeks | 8 | Drinking water without caffeine | 8 | Fluid intake, food intake, urinary volume, systolic blood pressure | In drinking water |
Sugiyama, Ohishi 15 | 1989 | Comparison of the plasma cholesterol-elevating effects of caffeine and methionine in rats on a high-cholesterol diet | Wistar rats | High-cholesterol diet | Dyslipidemia | 0.3% | 2 weeks | 7 | Basal diet without caffeine | 8 | Food intake, change in body weight, serum total cholesterol, serum triglycerides, serum HDL-C, Liver triglycerides, liver cholesterol, liver weight | In feed |
Choi, Lee 16 | 1993 | Chronic caffeine ingestion exacerbates 2-kidney, 1-clip hypertension and ameliorates deoxycorticosterone acetate-salt hypertension in rats | Sprague–Dawley rats | Deoxycorticosterone acetate 200 mg/kg, subcutaneous implant, + salt hypertension (0.9% NaCl intake) | Hypertension | 0.1% | 24 days | 6 | Drinking solution (0.9% NaCl) without caffeine | 6 | Systolic blood pressure | Drinking solution with 0.9% NaCl |
Tofovic and Jackson 17 | 1999 | Effects of long-term caffeine consumption on renal function in spontaneously hypertensive heart failure prone rats | lean spontaneously hypertensive heart failure (SHHF/Mcc-facp) rats | Genetic | Hypertension and heart failure | 0.1% | 20 weeks | 10 | Drinking tap water without caffeine | 9 | Systolic blood pressure, diastolic blood pressure, mean arterial pressure | In drinking water |
Tanner and Tanner 18 | 2001 | Chronic caffeine consumption exacerbates hypertension in rats with polycystic kidney disease | Heterozygous Han: Sprague–Dawley (Han: SPRD) rat | Genetic | Hypertension and autosomal dominant polycystic kidney disease | 0.1 mg/mL | 20 weeks | 6 | Drinking tap water without caffeine | 17 | Fluid intake, final body weight, mean arterial blood pressure | In drinking water |
0.2 mg/mL | 5 | |||||||||||
Tofovic, Kusaka 19 | 2001 | Renal and metabolic effects of caffeine in obese (fa/facp), diabetic, hypertensive ZSF1 rats | Obese (fa/facp) ZSF1 rat | Genetic | Obesity Hypertension Type 2 diabetes Hypercholesterolemia Hypertriglyceridemia Renal dysfunction | 0.1% | 8 weeks | 7 | Drinking tap water without caffeine | 8 | Fluid intake, food intake, urinary volume, final body weight, serum triglycerides, serum total cholesterol, serum fasting glucose, serum postprandial glucose, area under the glucose curve, serum fasting insulin, serum postprandial insulin, area under the insulin curve, urinary glucose, systolic blood pressure, diastolic blood pressure, mean arterial blood pressure | In drinking water |
Tofovic, Kost 20 | 2002 | Long-term caffeine consumption exacerbates renal failure in obese, diabetic, ZSF1 (fa-facp) rats | Obese (fa/facp) ZSF1 rat | Genetic | Obesity Hypertension Type 2 diabetes Hyperlipidemia Renal dysfunction | 0.1% | 30 weeks | 12 | Drinking tap water without caffeine | 12 | Fluid intake, food intake, urinary volume, final body weight, serum triglycerides, serum total cholesterol, serum fasting glucose, serum fasting insulin, urinary glucose, OGTT, systolic blood pressure, diastolic blood pressure, mean arterial blood pressure | In drinking water |
Park, Jang 21 | 2007 | Long-term consumption of caffeine improves glucose homeostasis by enhancing insulinotropic action through islet insulin/insulin-like growth factor 1 signaling in diabetic rats | Sprague–Dawley rats | High-fat diet + 90% pancreatectomy | Type 2 diabetes | 0.01% | 12 weeks | 9 | Drinking water without caffeine | 10 | Fluid intake, energy intake, final body weight, body fat-pad weight, serum fasting glucose, serum fasting insulin | In drinking water |
Tofovic, Salah 22 | 2007 | Early renal injury induced by caffeine consumption in obese, diabetic ZSF1 rats | Obese (fa/facp) ZSF1 rat | Genetic | Obesity Hypertension Hyperlipidemia Diabetes Renal dysfunction | 0.1% | 9 weeks | 9 | Drinking tap water without caffeine | 10 | Fluid intake, food intake, urinary volume, final body weight, serum triglycerides, serum total cholesterol, area under the glucose curve, serum fasting insulin, urinary glucose, OGTT, mean arterial blood pressure | In drinking water |
Kagami, Morita 23 | 2008 | Protective effect of caffeine on streptozotocin-induced beta-cell damage in rats | Wistar rats | Streptozocin 65 mg/kg, intraperitoneal injection | Diabetes | 10 mg/kg | 1 week | - | Streptozocin and saline injection | - | Final body weight, serum fasting glucose, serum fasting insulin, OGTT | Intraperitoneal injection |
50 mg/kg | ||||||||||||
100 mg/kg | ||||||||||||
Conde, Nunes da Silva 4 | 2012 | Chronic caffeine intake decreases circulating catecholamines and prevents diet-induced insulin resistance and hypertension in rats | Wistar rats | High-fat diet | Metabolic syndrome | 1 g/L | 15 days | 12–15 | Drinking water without caffeine | 9 to 12 | Fluid intake, food intake, change in body weight, body fat-pad weight, serum non-esterified fatty acids, serum fasting glucose, serum fasting insulin, mean arterial blood pressure | In drinking water |
High-sucrose diet | Insulin resistance Hypertension | 1 g/L | 15 days | 12–15 | Drinking water without caffeine | 9 to 12 | Fluid intake, food intake, change in body weight, body fat-pad weight, serum non-esterified fatty acids, serum fasting glucose, serum fasting insulin, mean arterial blood pressure | In drinking water | ||||
Panchal, Wong 24 | 2012 | Caffeine attenuates metabolic syndrome in diet-induced obese rats | Wistar rats | High-carbohydrate, high-fat diet | Metabolic syndrome Metabolic abnormalities Cardiovascular remodeling Nonalcoholic steatohepatitis | 0.5 g/kg of food or 47.9 ± 1.0 mg/kg/day | 8 weeks | 10 | Fed experimental diet without caffeine | 10 | Fluid intake, food intake, energy intake, final body weight, whole-body fat weight, body fat-pad weight, serum triglycerides, serum total cholesterol, serum non-esterified fatty acids, serum AST, serum ALT, serum AP, serum LDH, serum albumin, serum total bilirubin, liver weight, serum fasting glucose, area under the glucose curve, serum fasting insulin, OGTT, ITT, systolic blood pressure | In feed |
Naidoo and Islam 25 | 2014 | Development of an alternative non-obese non-genetic rat model of type 2 diabetes using caffeine and streptozotocin | Sprague–Dawley rats | Streptozocin 65 mg/kg, intraperitoneal injection | Diabetes | 20 mg/kg | 13 weeks | 10 | Injection containing only normal saline (0.9% NaCl) | 10 | Fluid intake, food intake, final bodyweight, serum triglycerides, serum total cholesterol, LDL-C, HDL-C, serum AST, serum ALT, serum AP, serum LDH, liver weight, serum fasting glucose, serum postprandial glucose, serum fasting insulin, OGTT | Single injection |
40 mg/kg | 10 | |||||||||||
Xu, Zhang 26 | 2015 | The anti-obesity effect of green tea polysaccharides, polyphenols and caffeine in rats fed with a high-fat diet | Sprague–Dawley rats | High-fat diet | Obesity | 400 g/kg | 6 weeks | 12 | Fed experimental diet plus saline | 12 | Final body weight, body fat percentage, whole-body fat weight, serum triglyceride, serum total cholesterol, LDL-C, HDL-C | In feed |
Kumbhar, Une 27 | 2016 | Exaggeration of type 2 diabetes due to caffeine-nicotine coadministration: A study in rats | Sprague–Dawley rats | High-fat diet for 2 weeks prior to a single intravenous streptozocin injection (50 mg/kg) | Diabetes | 40 mg/kg | 3 weeks | 10 | Injected with sodium chloride in distilled water | 10 | Change in body weight, serum total cholesterol, LDL-C, HDL-C, serum AST, serum ALT, serum fasting glucose | Intraperitoneal injection |
Suzuki, Shindo 8 | 2017 | Combined long-term caffeine intake and exercise inhibits the development of diabetic nephropathy in OLETF rats | Otsuka Long–Evans Tokushima fatty (OLETF) rats | Genetic | Obesity Diabetes | 0.2% (90.7 ± 4.7 mg/kg/day) | 4 weeks | 8 | Fed experimental diet without caffeine | 8 | Food intake, urinary volume, final body weight, serum non-esterified fatty acids, serum fasting glucose, serum fasting insulin, systolic blood pressure, diastolic blood pressure | In feed |
Helal, Ayoub 28 | 2018 | Caffeine affects HFD-induced hepatic steatosis by multifactorial intervention | Wistar rats | High-fat diet | Nonalcoholic fatty liver disease | 20 mg/kg/day | 16 weeks | 10 | Received vehicle only | 10 | Serum triglycerides, serum total cholesterol, HDL-C, serum AST, serum ALT, serum albumin, serum total bilirubin | Orally |
30 mg/kg/day | 10 | |||||||||||
Yang, Zhu 29 | 2019 | Coadministration of epigallocatechin-3-gallate (EGCG) and caffeine in low dose ameliorates obesity and nonalcoholic fatty liver disease in obese rats | Sprague–Dawley rats | High-fat diet | Obesity Nonalcoholic fatty liver disease | 20 mg/kg | 4 weeks | 8 | Oral gavage with distilled water | 8 | Food intake, energy intake, final body weight, body fat percentage, white adipose tissue weight, body fat-pad weight, serum triglycerides, serum total cholesterol, LDL-C, HDL-C, serum non-esterified fatty acids, serum AST, serum ALT | Oral gavage |