N02013: Evaluation of effects of dietary exchange of individual saturated fatty acids on haemostasis and vascular function

Study Duration: September 1999 to June 2003

Contractor: University of Dundee

The question of whether individual dietary unsaturated fatty acids (UFAs) or saturated fatty acids (SFAs) alter blood vessel (vascular) dilation and constriction (tone), and also affect the function of the blood vessel lining (endothelium) is highly pertinent to dietary recommendations for cardiovascular (CV) health. In particular diets high in saturated fats (SFs) are associated with the development of hardening of the arteries (atherosclerosis) and this has been well documented in epidemiological studies. In contrast UFAs may be less detrimental. Current dietary recommendations suggest lowering intake of SFs and increasing the UFAs as a means of preventing the development of coronary artery disease (CAD). Complete removal of SFs from the diet is however unrealistic and may be undesirable.

Rationale and Objectives

Thus the questions still to be answered include "What dietary recommendations should be made regarding the mono-UFA and poly-UFA content within the diet, and which of the SFs should be included in the diet and which excluded or reduced?" This project evaluated a dietary exchange of 2 SFs (palmitate and stearate) against a control group.

Altogether 128 healthy subjects, men and women, non-smokers (age >40 years) were enrolled into three study arms. Baseline dietary saturated fatty acid status was estimated by food frequency questionnaire and 7-day diet diary. Plasma fatty acid composition was measured using a sophisticated Gas Chromatography method. Of 128 volunteers initially enrolled, 101 subjects completed the study. Following a 1-month run-in phase with volunteers consuming their usual total FA composition of their diet to assess compliance, the patients entered the dietary phase of the study. At this time assessment of baseline endothelial cell function/vascular tone was carried out using 2 techniques called iontophoresis and laser Doppler imaging. In this 1st technique a chemical, which dilates blood vessels is driven into the skin using an electric current. In the 2nd the flow of blood is measured using a Laser beam of light. These 2 techniques together allow us to measure blood vessel dilation and constriction. Additionally arterial stretch (compliance) was measured. The compliance of the large blood vessel running down through the centre of the body, the aorta, was estimated using applanation tonometry (SphygmoCor, PWV Medical). In this technique a pencil-like probe is placed over the radial artery at the wrist and a calculation carried out which then estimates aortic stretch from the measures obtained at the wrist. Samples were taken to assess baseline blood clotting by measurement of blood biochemistry markers and blood cell activation. After the baseline studies were completed the subjects were randomised in a double-blind fashion (i.e. neither the investigators nor the volunteers knew to which group they had been assigned) to one of 3 study arms. These arms reflected a dietary exchange with palmitic acid, stearic acid and control, i.e. the subjects were maintained on their total fat and FA intake previously defined by the 7-day diet diary. This third group provided a comparison to the first 2 groups. We were careful not to increase total SF intake but to maintain that of the general population of 16% total dietary energy. Of this approximately 75% was used in an exchange format (e.g. margarine, biscuits and cakes) enabling a precise composition of the specific fatty acids to be achieved. An adequate daily SF exchange was ensured by using an allocated exchange system. Diet was assessed by weighed dietary records at 3 time points (7-day dairy at baseline and 2 further 4-day diaries during the course of the trial). Unilever provided the spreads and fats and the exchange took place over a 4-month period.

Results show that the subjects complied to the diet with significant alterations in palmitic and stearic acid levels in the appropriate groups. No changes were detected in vascular dilitation or constriction either before or after any of the dietary interventions. Furthermore none of the measures of arterial stretch were affected by any of the dietary interventions. Furthermore none of the measures of arterial stretch were affected by any of the dietary interventions. Analysis of the biochemical and cellular markers of blood clotting showed no significant clinical change within the control group. In contrast, however, the exchange that increased stearic acid seemed to produce what might be considered as beneficial changes, whereas the palmitic acid exchange did not. In the stearic group platelet nitric oxide (NO) production went from 13.1 nanomols per litre (11.3-18.2) to 17.2 nanomols per litre (14.5-20.3), p=0.049. NO is a gas released by the blood vessel lining which enhances vasodilitation, a good thing to happen as it increases blood flow.

The blood platelet is an important cell for blood clotting process. It becomes sticky, and forms a plug to seal off any breaches in blood vessels that may occur. If this process is overactive, platelets can stick to the blood vessel lining, forming clumps that block the flow of blood. Decreased P-selectin expression, reflecting decreased platelet activation, was also detected in this group as was decreased E-selectin expression, reflecting diminished white cell/endothelial adhesion propertiesThe white blood cell is also able to block blood vessels because they stick (adhere) to the blood vessel lining. Fibrinogen, a very sticky blood protein, also fell within this group from 3.11 grams per litre (2.77-3.49) to 3.05 grams per litre (2.61-3.33), p=0.017. In the group in which palmitic acid was exchanged these tests remained unchanged. The only clinically relevant change was in prothrombin time, i.e. the time taken for the blood to clot in a test tube, which was measured at a ratio of 0.97 (0.92-1.04) at the start of the study. This increased to 0.98 (0.94-1.05) at the end (p=0.011) ie the blood clotted sooner after the palmitate. The clinical relevance of this change is uncertain although the PT increase in all subjects studied suggests that a change across a population might be detrimental in terms of CV disease within that population.

Conclusions

In conclusion therefore, for most of the risk factors determined, including vascular function, the results showed no significant differences. Significant differences were observed in some haemostatic measures, however these differences were not observed between groups, but within groups. Overall, neither dietary intervention effected any significant change, suggesting that there is no advantage in terms of cardiovascular risk of the dietary exchange of, the saturated fatty acids, stearic for palmitic acid.

Final report is available from the FSA Library and Information centre.
To obtain a copy, please contact the Enquiry Desk, Dr. Elsie Widdowson Library and Information Services, Food Standards Agency (020 7276 8181/8182 or at library&info@foodstandards.gsi.gov.uk).

Sanderson P, Olthof M, Grimble RF, Calder PC, Griffin BA, de Roos NM, Belch JJF, Muller DPR & Vita JA (2003) Dietary lipids and vascular function: UK Food Standards Agency workshop report Br J Nutr in press

Contact: Email: science@foodstandards.gsi.gov.uk