An examination of the impact of unmelted, melted, and deconstructed cheese on lipid metabolism: a 6-week randomised trial.

Background: Evidence suggests cheese has a favourable or neutral effect on cardiometabolic health, compared to butter. To date, studies have only considered the cheese matrix in its unmelted form, while the effect of melted cheese remains unknown. Objective: To test the effect of 6-week daily consumption of ∼40 g dairy fat, eaten in either as unmelted cheese, melted cheese, or in a fully deconstructed form, on markers of metabolic health in overweight adults aged ≥50 years of age. Design: A 6-week randomised parallel intervention, where 162 participants (43.3% male) received ∼40 g of dairy fat per day, in 1 of 3 treatments: (A) 120 g full-fat Irish grass-fed cheddar cheese, eaten in unmelted form (n 58); (B) 120 g full-fat Irish grass-fed cheddar cheese eaten in melted form (n 53); or (C) the equivalent components; butter (49 g), calcium caseinate powder (30 g), and Ca supplement (CaCO3; 500 mg) (n 51). Results: There was no difference in weight, fasting glucose, or insulin between the groups post-intervention. Melted cheese, compared to unmelted cheese, increased total cholesterol (0.23 ± 0.79 mmol L-1vs. 0.02 ± 0.67 mmol L-1, P = 0.008) and triglyceride concentrations (0.17 ± 0.39 mmol L-1vs. 0.00 ± 0.42 mmol L-1, P = 0.016). Melted cheese increased total cholesterol concentrations by 0.20 ± 0.15 mmol L-1 and triglyceride concentrations by 0.17 ± 0.08 mmol L-1 compared to unmelted cheese. No significant differences were observed between the cheese forms for change in HDL, LDL or VLDL cholesterol. Conclusion: Compared to unmelted cheese, melted cheese was found to increase total cholesterol and triglyceride concentrations in middle-aged, overweight adults with no effect on weight or glycaemic control.

Impact of the MTHFR C677T polymorphism on blood pressure and related central haemodynamic parameters in healthy adults.

BACKGROUND: The C677T polymorphism in the gene-encoding methylenetetrahydrofolate reductase (MTHFR) is associated with an increased risk of hypertension and cardiovascular disease. Riboflavin, the MTHFR cofactor, is an important modulator of blood pressure (BP) in adults homozygous for this polymorphism (TT genotype). The effect of this genetic variant on BP and related central haemodynamic parameters in healthy adults has not been previously investigated and was examined in this study. METHODS: Brachial BP, central BP and pulse wave velocity (PWV, SphygmoCor XCEL) were measured in adults aged 18-65 years prescreened for MTHFR genotype. Riboflavin status was assessed using the erythrocyte glutathione reductase activation coefficient assay. RESULTS: Two hundred and forty-two adults with the MTHFR 677TT genotype and age-matched non-TT (CC/CT) genotype controls were identified from a total cohort of 2546 adults prescreened for MTHFR genotype. The TT genotype was found to be an independent determinant of hypertension (p = 0.010), along with low-riboflavin status (p = 0.002). Brachial systolic and diastolic BP were higher in TT versus non-TT adults by 5.5 ± 1.2 and 2.4 ± 0.9 mmHg, respectively (both p < 0.001). A stronger phenotype was observed in women, with an almost 10 mmHg difference in mean systolic BP in TT versus non-TT genotype groups: 134.9 (95% confidence interval [CI] 132.1-137.6) versus 125.2 (95% CI 122.3-128.0) mmHg; p < 0.001. In addition, PWV was faster in women with the TT genotype (p = 0.043). CONCLUSION: This study provides the first evidence that brachial and central BP are significantly higher in adults with the variant MTHFR 677TT genotype and that the BP phenotype is more pronounced in women.

Impact of the MTHFR C677T polymorphism on one-carbon metabolites: Evidence from a randomised trial of riboflavin supplementation.

Homozygosity for the C677T polymorphism in MTHFR (TT genotype) is associated with a 24-87% increased risk of hypertension. Blood pressure (BP) lowering was previously reported in adults with the TT genotype, in response to supplementation with the MTHFR cofactor, riboflavin. Whether the BP phenotype associated with the polymorphism is related to perturbed one-carbon metabolism is unknown. This study investigated one-carbon metabolites and their responsiveness to riboflavin in adults with the TT genotype. Plasma samples from adults (n 115) screened for the MTHFR genotype, who previously participated in RCTs to lower BP, were analysed for methionine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), betaine, choline and cystathionine by liquid chromatography tandem mass spectrometry (LC-MS/MS). The one-carbon metabolite response to riboflavin (1.6 mg/d; n 24) or placebo (n 23) for 16 weeks in adults with the TT genotype was also investigated. Plasma SAM (74.7 ± 21.0 vs 85.2 ± 22.6 nmol/L, P = 0.013) and SAM:SAH ratio (1.66 ± 0.55 vs 1.85 ± 0.51, P = 0.043) were lower and plasma homocysteine was higher (P = 0.043) in TT, compared to CC individuals. In response to riboflavin, SAM (P = 0.008) and cystathionine (P = 0.045) concentrations increased, with no responses in other one-carbon metabolites observed. These findings confirm perturbed one-carbon metabolism in individuals with the MTHFR 677TT genotype, and for the first time demonstrate that SAM, and cystathionine, increase in response to riboflavin supplementation in this genotype group. The genotype-specific, one-carbon metabolite responses to riboflavin intervention observed could offer some insight into the role of this gene-nutrient interaction in blood pressure.