Trans Fatty Acids and Cardiovascular Risk Factors
Condition: Cardiovascular Disease
MeSH terms: Cardiovascular Diseases
Study type: Interventional

Summary: 
      Background:

      Detrimental effects of consumption of industrial trans fatty acids (TFA) from partially
      hydrogenated vegetable oils (PHVO) on cardiovascular disease (CVD) risk factors are well
      documented. However, very little information is available on the effect of natural sources of
      TFA coming from milk fat, dairy products and ruminant meat. In fact, due to the naturally low
      level of TFA in milk fat, it is almost impossible to conduct a clinical trial with a limited
      number of subjects.

      Methodology:

      To compare the effects of industrial and natural dietary sources of TFA, two specific test
      fats have been designed and produced. A substantial amount of milk fat (130 kg) enriched in
      TFA has been produced by modification of the cow's diet and selection of cows with the
      highest TFA content. The level obtained was approximately 4- to 7-fold higher than typically
      present in milk fat ( - 20 instead of 3-6 g/100 g of total fatty acids). The control fat is
      composed of PHVO balanced in saturated fatty acids (lauric, myristic and palmitic). Both
      experimental fats contain about 20-22% of monounsaturated TFA and the volunteers' daily
      experimental fat intake (54 g), will represent about 12.0 g/day of TFA or 5.4% of the daily
      energy (based on 2000 kcal/day). These two test fats have been incorporated into food items
      and will be provided to 46 healthy subjects under a randomised, double blind, controlled,
      cross-over design. The primary outcome is high-density lipoprotein cholesterol (HDL-C), which
      is an independent risk factor for CVD. Other parameters such as lipoprotein cholesterol
      (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and HDL-C level and subclasses
      will be also to be evaluated.
    

Detailed description: 
      Design:

      This is a double blind, controlled, randomised, cross-over, single center clinical trial.

      Product(s) to be tested:

      Food items (butter, cheese and biscuits) manufactured using (i) an experimental milk fat and
      (ii) a mixture of vegetable oils (including partially hydrogenated oils), used as control.
      Both fats are balanced for their trans fatty acid content and saturated fatty acids content.
      The main difference of these two experimental fats (milk fat and control fat) is the
      distribution of trans fatty acids (TFA). The experimental milk fat, entitled "vaccenic acid
      enriched milk fat" (VAMF), has been obtained by feeding cows with a diet containing sunflower
      oil. The distribution (the quality) of monounsaturated C18:1 TFA in the VAMF is therefore
      close to the usual milk fat, but with higher levels (enriched milk).The experimental control
      fat, shorted CTRL, has been obtained by mixing partially hydrogenated vegetable oils (PHVO)
      and vegetable oils and fats.

      Amount, dosage, route of administration, duration of treatment:

      During the 1-week run-in period, subjects should eat daily the same products as the
      experimental ones (butter, cheese and biscuits) but manufactured using usual milk collected
      in France. The subjects should then eat daily for 3 weeks butter, cheese and biscuits
      containing one of the 2 experimental fats (milk fat or control fat, cross-over with 1-week
      wash-out period) so that they eat daily about 54 g of the experimental fat, which contain
      about 20-22% of TFA. The total study duration for each subject is 8 weeks: 1-week run-in
      period, 3-week experimental fat diet in cross-over with 1-week wash-out period between both
      experimental periods.

      All the measurements and blood samplings will be done on the first day of week 1, 3, 4, 5, 7
      and 8.

      Primary outcome:

      HDL-Cholesterol (HDL-C) levels

      Secondary outcomes:

        -  Triglycerides, total cholesterol, Apo A1 , Apo B, factor VII and factor VIIa, fibrinogen
           levels. Lp(a) and CETP, measured on plasma by fluorimetry. LDL-cholesterol (LDL-C) will
           be calculated

        -  LDL, HDL and VLDL levels and subclasses

      Other outcome:

      evaluation of the fatty acid profiles of plasma cholesteryl esters and phospholipids
    

Intervention name(s): vaccenic acid enriched milk fat (VAMF) [Transfact1]; hydrogenated oil
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Partially hydrogenated vegetable oils (PHVO) and vegetable oils and fats
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double
Primary purpose: Prevention
Keywords: Lipoproteins; Milk fat; Public health nutrition; trans fatty acid