Risk scores, calculated with the use of the modified Framingham risk score, did not significantly differ following the two intervention diets and relative to baseline values (Table 3.3).
3.5 Discussion
To our knowledge this is the first study to report on the long-term effects of partially replacing SFA with MUFA in a variety of dairy products on the fasting lipid profile, FMD and CVD markers, in adults at moderate CVD risk. We observed a tendency for a difference in TC compared to baseline values between the two diets, which did not reach statistical significance. However, we observed that the modified diet significantly attenuated the LDL-C and TC:HDL-C ratio, raising effect of the control diet with no impact on HDL-C or LDL-P and HDL-P size distribution. With the exception of a significant decrease in fasting nitrite concentrations following the modified diet, little impact on other vascular function and CVD risk markers were found.
Investigating how to optimally replace dietary SFA with a suitable macronutrient presents a number of challenges, as both the single nutrient and the food source should be considered within dietary patterns and risk markers. (23). The existing body of evidence, from RCTs and prospective cohort studies, which have investigated a replacement of SFA with cis- MUFA to reduce CVD mortality, is limited. Lack of clarity may in part be explained by limited studies with hard endpoints, variation in design of RCTs and ultimately the source of MUFA, as it appears that a beneficial outcome on risk markers is primarily observed from sources of plant oils and nuts, while other sources may lead to neutral results (23).
102
As dairy products represent the largest food source of dietary SFA intake in the UK (10), this food group provides a suitable vehicle for investigating partial SFA replacement with MUFA. A review of previously published human trials investigating the impact of FA- modified dairy products, indicated a tendency towards a beneficial effect on fasting lipid markers (134). In an 8-wk crossover study led by Noakes et al. (135), healthy adults (49 ± 10.3 y) consumed FA-modified milk, cheese, butter and ice-cream (16%TE SFA, 11.9%TE MUFA) or control dairy products (18.2%TE SFA, 9.1%TE MUFA). The study reported a significant decrease in TC (-4.3%) and LDL-C (-5.3%) following the modified dairy compared to the control diet. However, it is difficult to draw meaningful comparisons between the two studies, as baseline values were not included in the statistical analysis reported by Noakes et al (135).
Our results indicate that a high fat, high dairy diet including conventional dairy foods (control) led to an increase in LDL-C (5.5%), which was attenuated by the modified diet (0.9%). The observed LDL-C attenuation may be associated with the effects of dietary fatty acids on LDL-receptor expression and activity (56). There is increasing evidence suggesting that dietary SFA intake may differentially impact on LDL subclass concentrations, with small LDL-P recognised as more strongly associated with progression of atherosclerosis and CVD outcomes than larger LDL-P (219). In our study, the two intervention diets did not
significantly impact on the particle size distribution of both LDL and HDL subclasses, which may be explained from both the dairy nature of the diets and the modest, partial substitution of SFA with MUFA in the modified compared to the control diet.
A comparison of predictive equations shows that our results appear more in line with the equations by Clarke et al. (213). It is worth noting that early predictive equations (210, 211) did not include a coefficient of change in dietary MUFA, as it was considered a neutral FA class with little impact on the lipid profile. Interestingly, the observed attenuation in LDL-
103
C following the modified diet was found even though the dietary total trans fatty acid (TFA) intake had increased (2.5%TE vs 1.2%TE) compared to the control and relative to baseline (201). Although it was not possible to adequately discriminate between the participants’ intake of industrial and ruminant TFAs in the two diets using the dietary analysis software, supplementation of the bovine diet led to a greater proportion of ruminant TFA (rTFA) in the modified dairy products (203). The observed higher TFA intake following the modified diet exceeded the maximum 2% recommendation from food energy and the current mean TFA intake in UK adults (0.5%TE and 0.5% food energy) (10, 197). However, it is worth noting that the observed increased TFA intake following the modified diet did not appear to adversely affect fasting lipid biomarkers. This is in agreement with previous studies, which concluded that there were no significant adverse physiological effects of rTFA, unless
consumed in high quantities (220). Furthermore, the observed increases in LDL-C following the control diet were also slightly lower than theoretically predicted. The attenuation in LDL- C concentrations following both diets compared to predicted changes, may be partly
explained by the presence within the dairy matrix of bioactive compounds, such as proteins and micronutrients, which may mediate an attenuation in LDL-C concentrations through synergistic mechanisms (36). As the aim of our study was to provide diets high in dairy with a differential FA composition, the protein and micronutrient content of the study products was not significantly altered (201, 203). Considering the apparent effect on LDL-C, future investigation is warranted to explore potential mechanisms of other components within the matrix of the FA-modified dairy products.
Progression of endothelial dysfunction and arterial stiffness characterize vascular dysfunction, mediating CVD risk (150). Recently, a prospective study demonstrated that increased milk and dairy product (with the exception of butter) intake was associated with a decrease in arterial stiffness in men (94). In our study, we did not observe significant
104
differences in vascular function, vascular stiffness, blood pressure and biomarkers related to endothelial function and low-grade inflammation between the two diets. The only exception was a statistically significant increase in plasma nitrite concentrations following the modified diet, with respect to baseline values and the control diet. Nitric oxide (NO) is essential for maintaining vascular homeostasis and a reduced bioavailability may suggest endothelial dysfunction (221). These differences in nitrite concentrations between treatments should be interpreted with caution as they may reflect not only measures of vascular function but also the participants’ dietary intake prior to study visits. Furthermore, the short half-life and rapid conversion to nitrate may also have affected the observed results (222).
Lastly, our results showed no significant treatment effect in fasting indexes of insulin, insulin sensitivity and glucose concentrations. This is in agreement with RCTs on modified dairy products (34, 223). Although a small number of studies on dairy consumption have proposed a beneficial impact on insulin sensitivity (77), well-designed and suitably powered RCTs are still needed to confirm effects of specific dairy products on insulin sensitivity. Strengths of our study include its long-term, double-blind and randomized design. We employed a food chain approach to reducing SFA in dairy products, an agricultural-based reformulation initiative which has the potential to prevent movement of SFA into other food chain entry points, and results in clean label products that are favoured by consumers (224). Encapsulation technology could provide a potential strategy implemented in the bovine feed to limit the observed increase of TFA in the modified milk. Additionally, participant ratings by VAS of the study products was further supported by consumers generally accepting FA- modified milk and dairy products, when tasted in a blinded manner, as recently published (225). The implementation of high dairy diets with differential FA composition was used to explore traditional and novel biomarkers of CVD risk. This meant that participants consumed large quantities of dairy products, which may not reflect habitual dairy intake of the
105
participants (10). However, our findings suggest a favourable impact on fasting LDL-C following consumption of FA-modified dairy products compared with commercial retail dairy, warranting future investigation with lower, more representative dairy intakes to determine if similar effects are observed. Finally, as our participants were at moderate CVD risk, our results may not be comparable in a healthy adult population.
In conclusion, our study, which is the first to investigate the impact FA-modified UHT milk, Cheddar cheese and butter on established and novel CVD risk outcomes, indicates that high daily consumption of SFA-reduced, MUFA-enriched dairy products attenuated the rise of LDL-C concentration observed with conventional commercially available dairy products, without significantly impacting TC and HDL-C. Further research is warranted to explore the impact of FA-modified dairy products on CVD risk biomarkers in both healthy and at risk populations.
106