General Information:

Id: 3,872
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Mammalia
review
Reference: de Lorgeril M et al.(2013) Recent findings on the health effects of omega-3 fatty acids and statins, and their interactions: do statins inhibit omega-3 BMC Med 11: 5 [PMID: 23289647]

Interaction Information:

Comment Early randomized controlled trials (RCTs) demonstrated the health benefits of omega-3 fatty acids (n-3), whereas recent RCTs were negative. Most patients in recent RCTs are no longer n-3 deficient and the vast majority are now treated with statins. Recent RCTs testing n-3 against arrhythmias suggest that n-3 reduce the risk only in patients not taking a statin. Other recent RCTs in secondary prevention were negative although, in a post-hoc analysis separating statin users and non-users, non-significant protection of n-3 was observed among statin non-users whereas statin users had no effect. Recent RCTs testing statins - after the implementation of the New Clinical Trial Regulation in 2007 - are negative (or flawed) suggesting that the lack of effect of n-3 cannot be attributed to a parallel protection by statins.
Formal Description
Interaction-ID: 38984

drug/chemical compound

Statin

affects_activity of

drug/chemical compound

Polyunsaturated fatty acid, omega-3

Comment It has been shown, including in an randomized controlled trials (RCT) in coronary heart disease (CHD) patients, that statins increase arachidonic acid, the main n-6 fatty acid in cell membranes.
Formal Description
Interaction-ID: 38996

drug/chemical compound

Statin

increases_quantity of

drug/chemical compound

Arachidonic acid

Drugbank entries Show/Hide entries for
Comment This may in turn inhibit the protective effects of n-3 because n-6 and n-3 fatty acids are in competition through various pathways involved in the development and complications of coronary heart disease (CHD). Although this view is still discussed, n-3 are clearly more protective when n-6 are low and n-6 might even be deleterious when given in large amounts and in the absence of n-3. Thus statins may inhibit n-3 by interfering in the n-3/n-6 interplay and favoring n-6.
Formal Description
Interaction-ID: 38997

drug/chemical compound

Polyunsaturated fatty acid, omega-6

affects_activity of

drug/chemical compound

Polyunsaturated fatty acid, omega-3

Comment A second mechanism would be through alteration of mitochondrial function, a key component of myocardial preconditioning. Chronic myocardial preconditioning, that is, the ability of the myocardium to withstand an ischemia-reperfusion injury and limit the extent of cell death during and after myocardial ischemia, is a major determinant of the outcome of any heart attack. Mitochondria are critical in the induction of myocardial preconditioning, and also of neuroprotection, and n-3 induce a chronic myocardial preconditioning state which is likely explained by improved mitochondrial function. On the other hand, statins are toxic for the mitochondria in a dose-dependent manner and patients treated with statins do have impairment of mitochondrial respiration.
Formal Description
Interaction-ID: 38998

drug/chemical compound

Polyunsaturated fatty acid, omega-3

decreases_activity of

Comment A second mechanism would be through alteration of mitochondrial function, a key component of myocardial preconditioning. Chronic myocardial preconditioning, that is, the ability of the myocardium to withstand an ischemia-reperfusion injury and limit the extent of cell death during and after myocardial ischemia, is a major determinant of the outcome of any heart attack. Mitochondria are critical in the induction of myocardial preconditioning, and also of neuroprotection, and n-3 induce a chronic myocardial preconditioning state which is likely explained by 'improved' mitochondrial function. On the other hand, statins are toxic for the mitochondria in a dose-dependent manner and patients treated with statins do have impairment of mitochondrial respiration.
Formal Description
Interaction-ID: 38999

drug/chemical compound

Statin

increases_activity of

Comment In animal experiments, coenzyme Q10, a key component in mitochondrial bioenergy transfer and the synthesis of which is inhibited by statins, was reduced in case of impaired heart mitochondrial function.
Formal Description
Interaction-ID: 39000

drug/chemical compound

Statin

decreases_quantity of

drug/chemical compound

Ubiquinone

Comment In animal experiments, coenzyme Q10, a key component in mitochondrial bioenergy transfer and the synthesis of which is inhibited by statins, was reduced in case of impaired heart mitochondrial function.
Formal Description
Interaction-ID: 39002

drug/chemical compound

Statin

decreases_activity of

Comment In animal experiments, coenzyme Q10, a key component in mitochondrial bioenergy transfer and the synthesis of which is inhibited by statins, was reduced in case of impaired heart mitochondrial function.
Formal Description
Interaction-ID: 39003

drug/chemical compound

Ubiquinone

affects_activity of

in cardiac muscle
Comment In statin-treated dogs, lower coenzyme Q10 was associated with deficits in a task that measures executive function, an equivalent of cognitive function in humans.
Formal Description
Interaction-ID: 39004

phenotype

decreased ubiquinone level

decreases_activity of

process

cognition

Comment In statin-treated dogs, lower coenzyme Q10 was associated with deficits in a task that measures executive function, an equivalent of cognitive function in humans.
Formal Description
Interaction-ID: 39005

phenotype

decreased ubiquinone level

decreases_activity of

process

cognition

Comment Endogenous production of coenzyme Q10 is inhibited by blocking the HMG-CoA reductase enzyme with statins and decreased plasma coenzyme Q10 was confirmed in statin-treated coronary heart disease (CHD) patients.
Formal Description
Interaction-ID: 39007

drug/chemical compound

Statin

decreases_activity of

gene/protein

HMGCR

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Comment Endogenous production of coenzyme Q10 is inhibited by blocking the HMG-CoA reductase enzyme with statins and decreased plasma coenzyme Q10 was confirmed in statin-treated coronary heart disease (CHD) patients.
Formal Description
Interaction-ID: 39008

gene/protein

HMGCR

increases_activity of

Drugbank entries Show/Hide entries for HMGCR
Comment A growing body of evidence demonstrates a link between disturbances in mitochondrial functioning, insulin resistance and diabetes. In particular, mitochondrial function is required for appropriate glucose-induced insulin secretion. In addition, statins provoke myalgias, often exacerbated by exercise, resulting in reduced physical activity which in turn increases insulin resistance and the risk of type 2 diabetes. It is, therefore, not unexpected that statins increase both insulin resistance and the risk of new-onset type 2 diabetes.
Formal Description
Interaction-ID: 39009

increases_activity of

Comment A growing body of evidence demonstrates a link between disturbances in mitochondrial functioning, insulin resistance and diabetes. In particular, mitochondrial function is required for appropriate glucose-induced insulin secretion. In addition, statins provoke myalgias, often exacerbated by exercise, resulting in reduced physical activity which in turn increases insulin resistance and the risk of type 2 diabetes. It is, therefore, not unexpected that statins increase both insulin resistance and the risk of new-onset type 2 diabetes.
Formal Description
Interaction-ID: 39012
Comment A growing body of evidence demonstrates a link between disturbances in mitochondrial functioning, insulin resistance and diabetes. In particular, mitochondrial function is required for appropriate glucose-induced insulin secretion. In addition, statins provoke myalgias, often exacerbated by exercise, resulting in reduced physical activity which in turn increases insulin resistance and the risk of type 2 diabetes. It is, therefore, not unexpected that statins increase both insulin resistance and the risk of new-onset type 2 diabetes.
Formal Description
Interaction-ID: 39013

drug/chemical compound

Statin

increases_activity of

phenotype

myalgia

exacerbated by exercise
Comment A growing body of evidence demonstrates a link between disturbances in mitochondrial functioning, insulin resistance and diabetes. In particular, mitochondrial function is required for appropriate glucose-induced insulin secretion. In addition, statins provoke myalgias, often exacerbated by exercise, resulting in reduced physical activity which in turn increases insulin resistance and the risk of type 2 diabetes. It is, therefore, not unexpected that statins increase both insulin resistance and the risk of new-onset type 2 diabetes.
Formal Description
Interaction-ID: 39014

phenotype

myalgia

increases_activity of

phenotype

decreased physical activity

Comment A growing body of evidence demonstrates a link between disturbances in mitochondrial functioning, insulin resistance and diabetes. In particular, mitochondrial function is required for appropriate glucose-induced insulin secretion. In addition, statins provoke myalgias, often exacerbated by exercise, resulting in reduced physical activity which in turn increases insulin resistance and the risk of type 2 diabetes. It is, therefore, not unexpected that statins increase both insulin resistance and the risk of new-onset type 2 diabetes.
Formal Description
Interaction-ID: 39015

phenotype

decreased physical activity

increases_activity of

disease

Insulin resistance

Comment A growing body of evidence demonstrates a link between disturbances in mitochondrial functioning, insulin resistance and diabetes. In particular, mitochondrial function is required for appropriate glucose-induced insulin secretion. In addition, statins provoke myalgias, often exacerbated by exercise, resulting in reduced physical activity which in turn increases insulin resistance and the risk of type 2 diabetes. It is, therefore, not unexpected that statins increase both insulin resistance and the risk of new-onset type 2 diabetes.
Formal Description
Interaction-ID: 39016

phenotype

decreased physical activity

increases_activity of

Comment A growing body of evidence demonstrates a link between disturbances in mitochondrial functioning, insulin resistance and diabetes. In particular, mitochondrial function is required for appropriate glucose-induced insulin secretion. In addition, statins provoke myalgias, often exacerbated by exercise, resulting in reduced physical activity which in turn increases insulin resistance and the risk of type 2 diabetes. It is, therefore, not unexpected that statins increase both insulin resistance and the risk of new-onset type 2 diabetes.
Formal Description
Interaction-ID: 39017

drug/chemical compound

Statin

increases_activity of

disease

Insulin resistance

Comment A growing body of evidence demonstrates a link between disturbances in mitochondrial functioning, insulin resistance and diabetes. In particular, mitochondrial function is required for appropriate glucose-induced insulin secretion. In addition, statins provoke myalgias, often exacerbated by exercise, resulting in reduced physical activity which in turn increases insulin resistance and the risk of type 2 diabetes. It is, therefore, not unexpected that statins increase both insulin resistance and the risk of new-onset type 2 diabetes.
Formal Description
Interaction-ID: 39018

drug/chemical compound

Statin

increases_activity of

Comment In contrast, n-3, from either plant or marine sources, decrease insulin resistance and the risk of diabetes.
Formal Description
Interaction-ID: 39019

drug/chemical compound

Polyunsaturated fatty acid, omega-3

decreases_activity of

disease

Insulin resistance

Comment In contrast, n-3, from either plant or marine sources, decrease insulin resistance and the risk of diabetes.
Formal Description
Interaction-ID: 39020

drug/chemical compound

Polyunsaturated fatty acid, omega-3

decreases_activity of

Comment N-3 interact with the n-3 fatty acid receptor/sensor GPR120, whose dysfunction results in insulin resistance and obesity in both rodents and humans.
Formal Description
Interaction-ID: 39021

drug/chemical compound

Polyunsaturated fatty acid, omega-3

increases_activity of

gene/protein

FFAR4

Comment N-3 interact with the n-3 fatty acid receptor/sensor GPR120, whose dysfunction results in insulin resistance and obesity in both rodents and humans.
Formal Description
Interaction-ID: 39022

gene/protein

FFAR4

affects_activity of

disease

Insulin resistance

Comment N-3 interact with the n-3 fatty acid receptor/sensor GPR120, whose dysfunction results in insulin resistance and obesity in both rodents and humans.
Formal Description
Interaction-ID: 39023

gene/protein

FFAR4

affects_activity of

disease

Obesity

Comment Exposure to persistent organic pollutants results in mitochondrial dysfunction and increased insulin resistance in both animal and humans. Thus, statins and organic pollutants may inhibit the protective effects of n-3 against insulin resistance and diabetes by similarly altering mitochondrial function.
Formal Description
Interaction-ID: 39024

environment

exposure to persistant organic pollutants

increases_activity of

Comment Exposure to persistent organic pollutants results in mitochondrial dysfunction and increased insulin resistance in both animal and humans. Thus, statins and organic pollutants may inhibit the protective effects of n-3 against insulin resistance and diabetes by similarly altering mitochondrial function.
Formal Description
Interaction-ID: 39025

environment

exposure to persistant organic pollutants

affects_activity of

drug/chemical compound

Polyunsaturated fatty acid, omega-3

via mitochondrial dysfunction
Comment The interactions between statins and n-3 may explain why statins decrease memory and energy and also increase fatigue with exertion since n-3 are major lipids of the brain and nervous system.
Formal Description
Interaction-ID: 39026

drug/chemical compound

Statin

decreases_activity of

process

memory

Comment The interactions between statins and n-3 may explain why statins decrease memory and energy and also increase fatigue with exertion since n-3 are major lipids of the brain and nervous system.
Formal Description
Interaction-ID: 39027

drug/chemical compound

Statin

increases_activity of

phenotype

fatigue