Platelet Responses in Cardiovascular Disease: Sex-Related Differences in Nutritional and Pharmacological Interventions
Table 1
Nutritional studies aimed at investigating gender-related differences in platelet responses.
Dietary factors
Experimental protocol
Main findings
Refs
Mediterranean diet (MD)
Population-based cohort study: 6975 males and 7611 females (mean age: yrs) adhering to MD and subdivided into 3 groups according to their PLT count: high-, medium-, and low-PLT count groups (2.5%, 95.6%, and 1.9% of the population, respectively).
In both sexes: PLT count was inversely associated with both MDS and IMI scores. Subjects with very high MD adherence had lower odds of having high-PLT count compared with individuals with poor adherence (OR 50.50; 95% CI: 0.31-0.80 and OR 5 0.73; 95% CI: 0.52-1.02 for MDS and IMI, respectively).
In males: the mean PLT count increased with increasing of predicted CVD risk (low CVD risk: , medium CVD risk: , and high CVD risk: ; for trend > 0.027 in multivariable analysis of variance).
In females: no differences in PLT count within the predicted CVD risk.
ω-3 PUFA
Ex vivo study: PLT isolated from healthy 20 males ( yrs) and 22 females ( yrs) preincubated with 1 μM EPA, DHA, or DPA for 6 min at 37°C, before stimulation with 5 μg/mL collagen.
In both sexes: DHA and DPA equally reduced PLT aggregation (36.4% and 33.5% in men and women, respectively). EPA was the most efficacious PUFA (51.7%, vs. DPA and vs. DHA).
In males: DHA (25.3%) and DPA (21.7%) were less effective, with respect to EPA (48.9%, and , respectively).
In females: DHA (46.5%), DPA (44.2%), and EPA (54.3%) equally reduced PLT aggregation.
Blinded placebo-controlled trial: healthy 15 males ( yrs old) and 15 females ( yrs), alternatively receiving a single dose of g capsules containing either (i) placebo or (ii) EPA-rich oil (providing 1 g EPA with EPA/DHA ) or (iii) DHA-rich oil (providing 1 g DHA with EPA/DHA ). Fasting blood samples collected for PLT aggregation assay at 0, 2, 5, and 24 hrs after supplementation.
In both sexes: EPA- and DHA-rich oils reduced PLT aggregation. EPA was the most effective at 2 (-3.6%, ), 5 (-8.8%, ), and 24 (-13.3%, ) hrs postsupplementation. DHA was inefficacious at 2 and 5 hrs, but equally effective (-11.9%, ) as EPA at 24 hrs.
In males: only EPA reduced PLT aggregation at 2 (-11%, ), 5 (-10.6%, ), and 24 (-20.5%, ) hrs.
In females: only DHA reduced PLT aggregation at 24 hrs (-13.7%, ).
Blinded placebo-controlled trial: healthy 15 males ( yrs) and 15 women ( yrs), alternatively receiving a single dose of g capsules containing either (i) placebo or (ii) EPA-rich oil (providing 1 g EPA with EPA/DHA ) or (iii) DHA-rich oil (providing 1 g DHA with EPA/DHA ). Fasting blood samples collected at 0 and 24 hrs after supplementation for PLT aggregation assay and measurement of pMP number and procoagulant activity.
In both sexes: neither oil affected pMP numbers, and only EPA-rich oil produced a decrease in pMP activity (−19.4%, ).
In males: EPA, but not DHA, increased the mean lag time (60 vs. 79 sec, +29.5%) and reduced ADP-induced PLT aggregation (−20.5%, ) and pMP activity (−22%, ). Inverse relationship between PLT aggregation activity and testosterone levels (,).
In females: DHA, but not EPA, was effective in reducing PLT aggregation (−13.7%), without affecting pMP number and activity.
Double-blind, randomized, controlled intervention trial: 79 men and 95 women aged 20–80 yrs receiving six 0.75 g capsules/day providing a total of 1.5 g EPA and 1.77 g DHA (i.e., 3.27 g EPA plus DHA), as TAG, equivalent to the amount in one portion of oily fish and six 0.75 g placebo capsules (high oleic sunflower oil), over 12 months. Fasting blood samples collected at 0 and 12 months after supplementation for lipid composition of platelet membrane.
In both sexes: no differences in basal content of EPA and DHA. Equal dose-dependent increases of EPA and DHA in platelet membrane between male and females after 12-month supplementation.
In males: EPA increased in PLT membrane, but without statistical significance.
Flavanols
Blinded randomized, controlled acute trial: healthy 26 women (23–62 yrs; mean: yrs) and 16 males (25–65 yrs; mean: yrs), who acutely ingested 60 g of (i) flavanol-enriched dark chocolate (FDC; mg of flavan-3-ols), (ii) standard dark chocolate (SDC; mg of flavan-3-ols), and (iii) white chocolate (WC; not detectable). Fasting blood collected at 0, 2, and 6 hrs after supplementation for PLT activity assays.
Ex vivo bleeding time In both sexes: ex vivo bleeding time increased 6 hrs after consumption of FDC and SDC, but not of WC (), in both sexes. In females: ex vivo bleeding time increased 6 hrs after the consumption of FDC and SDC, but not with WC (). In males: ex vivo bleeding time increased 6 hrs after the consumption of FDC and WC ().
PLT aggregation In both sexes: ADP-induced platelet aggregation reduced at 2 hrs, but not 6 hours, after consumption of FDC and SDC. In males: ADP-induced PLT aggregation was reduced at 2 and 6 hrs after consumption of FDC and SDC ( and vs. women). In females: TRAP-induced PLT aggregation was reduced at 2 hrs, but not 6 hours, after consumption of FDC (, value for interaction between treatment and gender: ).
PLT activation In both sexes: TRAP-induced fibrinogen binding decreased at 2 and 6 hrs after consumption of FDC and WC (respectively, and vs. SDC). In males: ADP-triggered P-selectin exposure decreased at 2 hrs, but not 6 hrs, after consumption of FDC and WB, but not with SDC (). In females: TRAP-induced fibrinogen binding was decreased at 2 hrs, but not 6 hours, after consumption of FDC (, value for interaction between treatment and gender: ).
Isoflavones
Double-blind, randomized, placebo-controlled study: 29 postmenopausal women (45–60 yrs), who randomly received two daily capsules of a soybean isoflavone extract ( mg daidzein and mg genistein per capsule) or placebo for 12 weeks. Blood collected at 0 and 12 weeks after supplementation for PLT TxA2 receptor binding assay.
In females: PLT TxA2 receptor density decreased in isoflavone-treated subjects from to fmol/108 PLT ( vs. the placebo group). Decrease in TxA2 receptor density inversely correlated with serum concentrations of isoflavones.
Double-blind, randomized, placebo-controlled study: healthy 10 men ( yrs) receiving 60 mg of soy proteins in the form of beverage powder and providing 131 mg of total isoflavones (80.3 mg genistein, 35.6 mg daidzein, and 15.1 mg glycitein) and 10 men ( yrs), receiving 60 mg of calcium caseinate powder (control), for 28 days. Blood was collected at 0, 28, and 56 days after supplementation for quantification of isoflavone content in plasma and PLT aggregation.
In males: plasma isoflavone content increased after 28 day in the supplementation group (vs. basal values) and returned to baseline after 56 days (washout period). PLT aggregation was not affected by soy protein supplementation.
