Dodecanedioic acid

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Materials and methods

Study type:

study with volunteers

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Dodecanedioic acid

EC Number:

211-746-3

EC Name:

Dodecanedioic acid

Cas Number:

693-23-2

Molecular formula:

C12H22O4

IUPAC Name:

dodecanedioic acid

Method

Subjects:

Controls
- Number of subjects exposed: 5
- Sex: male
- Age: 46 +/-3.8 years
- Fat free mass: 48.3 +/-7.2 kg
- Body massi ndex: 26,1 +/- 2.7 kg/m²

Type 2 diabetic patients
- Number of subjects exposed: 5
- Sex: male
- Age: 57.8 +/-7.0 years
- Fat free mass: 52.9 +/-5.6 kg
- Body mass index: 28.4 +/- 4.3 kg/m²
Diabetes mellitus length 5 +/- 2 years
Glycated Hb 8.5 +/-0.8 %

Ethical approval:

not specified

Route of exposure:

oral

Reason of exposure:

intentional

Exposure assessment:

measured

Details on exposure:

Following an 12h fast, subject ingested 40 g Dodecandioic acid in 200 mL water

Results and discussion

Clinical signs:

No adverse effects were noted.

Any other information on results incl. tables

The ingestion of 40g dodecanedioic acid in type 2 diabetic subjects before a moderate exercise reduces muscle fatigue and does not promote insulin secretion but rather is associated with an increase in triglyceride hydrolysis.

No adverse effects were noted.

Applicant's summary and conclusion

Conclusions:

The ingestion of 40g dodecanedioic acid in type 2 diabetic subjects before a moderate exercise reduces muscle fatigue and does not promote insulin secretion but rather is associated with an increase in triglyceride hydrolysis.
No adverse effects were observed.

Executive summary:

Metabolically healthy skeletal muscle possesses the ability to switch easily between glucose and fat oxidation in response to homeostatic signals. In type 2 diabetes mellitus and obesity, the skeletal muscle shows a great reduction in this metabolic flexibility. A substrate like dodecanedioic acid (C-12), able to increase skeletal muscle glycogen stores via succinyl-CoA formation, might both postpone the fatigue and increase fatty acid utilization, since it does not affect insulin secretion. In healthy volunteers and in type 2 diabetic subjects, the effect of an oral C-12 load was compared with a glucose or water load during prolonged, moderate-intensity, physical exercise. C-12 metabolism was analyzed by a mathematical model. After C-12, diabetics were able to complete the 2 h of exercise. Nonesterified fatty acids increased both during and after the exercise in the C-12 session. C-12 oxidation provided 14% of total energy expenditure, and the sum of C-12 plus lipids oxidized after the C-12 meal was significantly greater than lipids oxidized after the glucose meal (P < 0.025). The fraction of C-12 that entered the central compartment was 47% of that ingested. During the first phase of the exercise ( approximately 60 min), the mean C-12 clearance from the central compartment toward tissues was 2.57 and 1.30 l/min during the second phase of the exercise. In conclusion, C-12 seems to be a suitable energy substrate during exercise, since it reduces muscle fatigue, is rapidly oxidized, and does not stimulate insulin secretion, which implies that lipolysis is not inhibited as reported after glucose ingestion