Biological Availability Clinical Trial
Official title:
Presence of Cyclopropane Fatty Acids (CPFA) in Human Plasma After CPFA-rich Diet
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.
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.
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