Presence of Cyclopropane Fatty Acids (CPFA) in Human Plasma

Biological Availability Clinical Trial

Official title:

Presence of Cyclopropane Fatty Acids (CPFA) in Human Plasma After CPFA-rich Diet

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03612700
• Other study ID #: DDR-CPFA
• Status: Completed
• Phase: N/A
• Start date: August 6, 2018
• Est. completion date: September 28, 2018

Study information

• Verified date: October 2018
• Source: University of Parma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Fatty acids containing a cyclopropane ring in their structure (CPFA) have been found in plants, fungi, a wide variety of bacteria and recently detected in dairy products and bovine meat. Little is known about CPFA in mammals, especially in human tissues. This work aims at investigating the presence of CPFA in plasma of humans after a regular consumption of CPFA from milk and cheese. A free living diet controlled in CPFA, mainly deriving from Grana Padano cheese and whole milk containing CPFA, will be consumed by 10 healthy normal weight volunteers for three weeks, after one week of dairy products and bovine meat restricted diet. Plasma of volunteers will be collected at 8 different timepoints for lipid extraction, CPFA identification and quantification by GC-MS. A preliminary pilot in vivo acute study (involving only 1 subject) will be performed for investigating the post-prandial response curve of CPFA after a portion of Grana Padano cheese.

Description:

Cyclopropane fatty acids (CPFA), as cis-9,10- methyleneoctadecanoic and cis- 11,12- methyleneoctadecanoic acids, are unusual alicyclic fatty acids which occur in plants, fungi, or microorganisms both Gram-negative and Gram-positive as well as protozoa and Myriapoda. Some papers suggest that cyclopropane fatty acids are involved in the bacterial pathogenesis of infections and in the resistance of some bacterial strains as Lactobacillus sp., Escherichia Coli, Salmonella enterica, Staphilococcus aureus and Pseudomonas to different environmental stresses such as temperature changes, high osmolarity, solvents, acid pH and others as the presence of antibiotics or heavy metals in the culture medium. However, little is documented about the presence of CPFA in mammals. Recently, they were detected in milk and several dairy products, in bovine meat, in fish and in mushrooms. Our previous results showed that the most important food sources of CPFA were dairy products (mainly Grana Padano cheese) and bovine meat reaching concentration of 1g/kg order, while food processing, manufacturing, seasoning steps, fermentation as well as cooking did not affect CPFA content in the analyzed food matrices. Furthermore, CPFA intake from these foodstuffs should be considered dietary relevant in view of a possible physiological effect.

Actually, CPFA (mainly cyclopropaneoctanoic acid 2-hexyl) have been recently identified in both human serum and adipose tissue, suggesting that these fatty acids are efficiently absorbed and may play a physiological role in the human body.

Moreover, fatty acids containing cyclopropane rings have been reported to exert biological effects on lipid metabolism, kidney function, inflammation, and enzymes activity as cyclooxygenase and stearoyl-CoA desaturase. Previous results suggested that the synthesis of CPFA in microorganisms and in plants is regulated by the expression of CPFA synthase, which catalyse the addition of the methylene group from S-adenosylmethionine to double bond of the unsaturated fatty acids precursor. However, this enzyme has still not been identified in animals and humans. To the best of our knowledge, no information is present in literature about the fate of CPFA within the human body, and a thorough investigation of how CPFA can be metabolised and accumulate in humans is needed.

The aim of this investigation is to determine CPFA presence in human plasma after a CPFA-rich diet (with controlled intake of Grana Padano cheese and whole milk containing CPFA). Plasma of the volunteers will be collected at eight different timepoints for lipid extraction, CPFA identification and quantification by GC-MS. A preliminary pilot in vivo acute study will be performed (involving only 1 subject) for investigating the post-prandial response curve of CPFA after a portion of Grana Padano cheese.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: September 28, 2018
• Est. primary completion date: September 28, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• BMI 19-29 (kg/m2)

Exclusion Criteria:

• pregnancy and lactation

• gastrointestinal disorders

• metabolic diseases

• drugs and food supplements interfering with lipid metabolism

Related Conditions & MeSH terms

• Biological Availability

Intervention

Other:
• CPFA-rich foods
Daily consumption of Grana Padano cheese (50 g) and whole milk (250 mL) for 3 weeks.

Locations

Country	Name	City	State
Italy	Department of Food and Drugs, University of Parma	Parma

Sponsors (1)

Lead Sponsor	Collaborator
University of Parma

Country where clinical trial is conducted

Italy, 

References & Publications (17)

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Caligiani A, Marseglia A, Palla G. An overview on the presence of cyclopropane fatty acids in milk and dairy products. J Agric Food Chem. 2014 Aug 6;62(31):7828-32. doi: 10.1021/jf4057204. Epub 2014 Jul 24. — View Citation

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Jones SE, Whitehead K, Saulnier D, Thomas CM, Versalovic J, Britton RA. Cyclopropane fatty acid synthase mutants of probiotic human-derived Lactobacillus reuteri are defective in TNF inhibition. Gut Microbes. 2011 Mar-Apr;2(2):69-79. Epub 2011 Mar 1. — View Citation

Kadegowda AK, Burns TA, Pratt SL, Duckett SK. Inhibition of stearoyl-CoA desaturase 1 reduces lipogenesis in primary bovine adipocytes. Lipids. 2013 Oct;48(10):967-76. doi: 10.1007/s11745-013-3823-1. Epub 2013 Aug 9. — View Citation

Kim BH, Kim S, Kim HG, Lee J, Lee IS, Park YK. The formation of cyclopropane fatty acids in Salmonella enterica serovar Typhimurium. Microbiology. 2005 Jan;151(Pt 1):209-18. — View Citation

Lolli V, Marseglia A, Palla G, Zanardi E, Caligiani A. Determination of Cyclopropane Fatty Acids in Food of Animal Origin by (1)H NMR. J Anal Methods Chem. 2018 Apr 1;2018:8034042. doi: 10.1155/2018/8034042. eCollection 2018. — View Citation

Marseglia A, Caligiani A, Comino L, Righi F, Quarantelli A, Palla G. Cyclopropyl and ?-cyclohexyl fatty acids as quality markers of cow milk and cheese. Food Chem. 2013 Oct 15;140(4):711-6. doi: 10.1016/j.foodchem.2013.01.029. Epub 2013 Jan 23. — View Citation

Mika A, Stepnowski P, Chmielewski M, Malgorzewicz S, Kaska L, Proczko M, Ratnicki-Sklucki K, Sledzinski M, Sledzinski T. Increased Serum Level of Cyclopropaneoctanoic Acid 2-Hexyl in Patients with Hypertriglyceridemia-Related Disorders. Lipids. 2016 Jul;51(7):867-73. doi: 10.1007/s11745-016-4141-1. Epub 2016 Mar 22. — View Citation

Montanari C, Sado Kamdem SL, Serrazanetti DI, Etoa FX, Guerzoni ME. Synthesis of cyclopropane fatty acids in Lactobacillus helveticus and Lactobacillus sanfranciscensis and their cellular fatty acids changes following short term acid and cold stresses. Food Microbiol. 2010 Jun;27(4):493-502. doi: 10.1016/j.fm.2009.12.003. Epub 2010 Jan 6. — View Citation

Moore BS, Floss HG. Biosynthesis of Cyclic Fatty Acids Containing Cyclopropyl-, Cyclopentyl-, Cyclohexyl-, and Cycloheptyl-rings. Reference Module in Chemistry, Molecular Sciences, and Chemical Engineering, from Comprehensive Natural Products Chemistry 1:61-82, 1999

Poger D, Mark AE. A ring to rule them all: the effect of cyclopropane Fatty acids on the fluidity of lipid bilayers. J Phys Chem B. 2015 Apr 30;119(17):5487-95. doi: 10.1021/acs.jpcb.5b00958. Epub 2015 Apr 16. — View Citation

Schneider AC, Beguin P, Bourez S, Perfield JW 2nd, Mignolet E, Debier C, Schneider YJ, Larondelle Y. Conversion of t11t13 CLA into c9t11 CLA in Caco-2 cells and inhibition by sterculic oil. PLoS One. 2012;7(3):e32824. doi: 10.1371/journal.pone.0032824. Epub 2012 Mar 12. — View Citation

Sledzinski T, Mika A, Stepnowski P, Proczko-Markuszewska M, Kaska L, Stefaniak T, Swierczynski J. Identification of cyclopropaneoctanoic acid 2-hexyl in human adipose tissue and serum. Lipids. 2013 Aug;48(8):839-48. doi: 10.1007/s11745-013-3806-2. Epub 2013 Jun 11. — View Citation

Wessjohann LA, Brandt W, Thiemann T. Biosynthesis and metabolism of cyclopropane rings in natural compounds. Chem Rev. 2003 Apr;103(4):1625-48. Review. — View Citation

WOOD R, REISER R. CYCLOPROPANE FATTY ACID METABOLISM: PHYSICAL AND CHEMICAL IDENTIFICATION OF PROPANE RING METABOLIC PRODUCTS IN THE ADIPOSE TISSUE. J Am Oil Chem Soc. 1965 Apr;42:315-20. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CPFA plasmatic concentration	Fasting concentration of CPFA	Fasting CPFA plasma concentration [time -7 days, time 0 (after 1 week of CPFA restricted diet), time 3, 6, 9, 12, 15, 18 days]