Homocysteine Reduction Research Articles

Analysis of the Ultrasensitive C-Reactive Protein and Homocysteine Biomarkers after Photobiomodulation Therapy in Hormone Blocker-Treated Mastectomized Women: A Randomized, Blind, and Controlled Clinical Study.

Main: The pharmacological treatment of cancer can lead to undesirable hemodynamic adverse effects. Laser therapy may promote hemodynamic balance in these patients. This study aimed to analyze the values of the biomarkers ultrasensitive C-reactive protein (PCR_us) and Homocysteine (HCy) after the use of intravascular laser irradiation of blood (ILIB) in mastectomized patients using hormonal blockers Tamoxifen and Aromatase Inhibitors. Methods: This was an experimental, placebo-controlled, randomized clinical trial with experimental (G1) and control (G2) groups. In G1, patients were irradiated with ILIB using a red laser at 660 nm on the carotid artery, while G2 received a placebo treatment. Blood collection for HCy and us-CRP biomarker evaluation was conducted monthly for 4 months. Statistical analysis was performed using R Studio 4.4.2 and JAMOVI, with a significance level of 5%. Results: A total of 21 patients participated in the study, with 12 in G1 and 9 in G2. There were no differences in age, systolic, diastolic blood pressure, and heart rate between the groups. The initial and final mean PCR_us levels for G1 were 6.8 and 3.8 mg/dL, and for HCy were 14.2 and 12.1 µmol/L, respectively. While for G2 initial and final mean PCR_us levels were 9.40 and 7.60 mg/dL, and for HCy were 14.33 and 16.69 µmol/L. There was no statistical difference for PCR_us. However, a significant difference between the groups (p < 0.05) for HCy in the 3rd and 4th months. Conclusion: During ILIB Therapy, there was a reduction in HCy, which may favor the improvement of cardiovascular function in these patients undergoing anticancer therapies.

Folic acid supplementation for stroke prevention: A systematic review and meta-analysis of 21 randomized clinical trials worldwide

Background & aimsThe AHA/ASA guidelines for primary stroke prevention are almost a decade old. The current recommendation regarding folic acid supplementation is based on only 8 clinical trials, and an additional 13 folate trials have been published since then. This meta-analysis aims to fill in critical evidence gaps by comprehensively evaluating 21 published trials with particular attention given to identifying the true influences through stratification. MethodsPubMed, the Cochrane Central Register of Controlled Trials, and Embase were searched from inception to April 4, 2023. This study included all randomized controlled trials (RCTs) of folic acid with stroke as one of the reporting endpoints. Relative risks and 95% confidence intervals were used to assess the association between folic acid supplementation and the risk of stroke in a random-effects model. ResultsResults from the 21 pooled RCTs totaling 115,559 participants showed that folic acid supplementation significantly reduced the risk of stroke by 10% (RR 0.90, 95%CI 0.83 to 0.98). Subgroup analyses showed that folic acid efficacy was greater in areas without fortified grain or with partially-fortified grain (RR=0.83, 95% CI 0.75 to 0.93; RR=1.04 in areas with grain fortification, P-interaction=0.003). In this group, folic acid supplementation was most efficacious in those without a history of stroke or myocardial infarction (RR=0.77, 95% CI 0.68 to 0.86; RR=0.94 for participants with a history of stroke or myocardial infarction, P-interaction=0.008). The efficacy of folic acid remained consistent regardless of baseline folate levels, folic acid dosage, baseline vitamin B12 levels, vitamin B12 dosage, homocysteine reduction, intervention duration, and whether folic acid was taken alone or in combination (all P-interaction>0.05). All 21 trials were free of attrition bias and reporting bias, and there was no significant publication bias. ConclusionsThis is by far the largest meta-analysis of RCTs regarding folic acid supplementation and stroke, demonstrating the overall benefit of folic acid for stroke prevention. Grain fortification and history of stroke or myocardial infarction may be the most important influences on the efficacy of folic acid for stroke prevention.

Liraglutide for the treatment of obesity among patients with hidradenitis suppurativa

Background and aimsHidradenitis suppurativa (HS) is associated with obesity. Weight loss is frequently reflected in an amelioration in the severity of the lesions. Case reports have suggested that liraglutide might improve not only weight but also skin. We aimed to study the effects of liraglutide 3mg in patients with obesity and HS on metabolic and dermatological parameters. Methods14 patients started treatment with liraglutide for 3 months. Severity of the lesions was evaluated using the Hurley Staging System and quality of life with the DLQI (Dermatology Quality Index). ResultsThere was a significant reduction in BMI (39.3±6.2 vs 35.6±5.8; p=0.002), waist circumference (121.3±19.2 vs 110.6±18.1cm; p=0.01), CRP (4.5±2.2 vs 3±2.1mg/L; p=0.04), homocysteine (16.2±2.9 vs 13.3±3μmol/L; p=0.005) and plasma cortisol (15.9±4.8 vs 12.6±4.5μg/dL; p=0.007). Hurley (2.6±0.5 vs 1.1±0.3; p=0.002) and DLQI (12.3±2.8 vs 9.7±6.9; p=0.04) improved significantly. In multiple regression analysis, weight loss did not correlate with any inflammatory parameter or Hurley. ConclusionsLiraglutide 3mg is effective and safe among patients with HS and obesity. Long-term studies are mandatory to assess the effects of liraglutide on skin lesions and inflammatory markers among subjects with HS beyond weight loss.

Preliminary Consequences of Blood Pressure Management and Blood Homocysteine Levels with Perindopril in Newly Diagnosed Hypertensive Patients in the Vietnamese Population.

Perindopril is an ACE inhibitor that aids in both blood pressure regulation and homocysteine reduction. Our study aimed to evaluate the results of controlling blood pressure and blood homocysteine levels by perindopril in patients with primary hypertension. A cross-sectional descriptive study with a longitudinal follow-up was conducted on 105 primary hypertensive patients treated with perindopril. The results of our study showed that after 6 weeks of treatment with perindopril, the proportion of patients with the target blood pressure (BP) level accounted for 70.5%, the rate of grade 1 hypertension decreased from 61.0% to 25.7%, grade 2 blood pressure decreased from 17.1% to 3.8%, and there was no case of grade 3 hypertension. At the same time, we also found that the rate of BP control in the group of patients who controlled Hcy below a threshold of 15 μmol/L was significantly higher than in the other group (p < 0.05). Concerning the efficacy of decreasing homocysteine in blood, we discovered that after 6 weeks of treatment with perindopril, the proportion of patients with elevated homocysteine reduced considerably from 74.3% to 40% (p < 0.05). In addition, the homocysteine concentration was 4.33 mol/L lower after treatment than before treatment (95% CI: 3.69-4.97) (p < 0.05). Perindopril helps control blood pressure and reduces blood homocysteine levels in patients with primary hypertension.

Effects of liraglutide among patients living with psoriasis and obesity

Background and aimsThere is a bidirectional relationship between obesity and psoriasis. Liraglutide has been shown to improve the severity of psoriatic lesions in patients with type 2 diabetes. We aimed to study the effects of liraglutide 3mg in patients with obesity and psoriasis. MethodsTwenty patients started treatment with liraglutide 3mg for 3 months. Severity of the lesions was evaluated using the Psoriasis Area Severity Index (PASI) and the visual analogue scale of pain (VAS), and quality of life with the Dermatology Quality Index (DLQI). ResultsThere was a significant reduction in BMI (38.9±5.8 vs. 36.4±5.6; p<0.001), CRP (4.5±2.4 vs. 3±2mg/L; p<0.01), homocysteine (13.3±3.6 vs. 11.9±3μmol/L; p<0.01), ferritin (185.4±142.2 vs. 97.43±114.4ng/mL; p=0.04) and plasma cortisol (12±3.1 vs. 11.6±2.2μg/dL, p=0.04). PASI (10±8.4 vs. 5.1±6; p<0.0001), VAS (4.1±2 vs. 2.3±0.92; p=0.009) and DLQI (12.7±7 vs. 6.4±5.6, p<0.0001) improved significantly. In multiple regression analysis, weight loss did not correlate with any inflammatory parameter or PASI. ConclusionsLiraglutide 3mg for three months is effective and safe in reducing weight and improving psoriatic lesions among patients with psoriasis and obesity. Besides, there is an improvement in psoriatic lesions regardless of weight loss that deserves further studies.

Association of serum homocysteine, folate, and vitamin B12 and mood following the Swank and Wahls elimination dietary interventions in relapsing-remitting multiple sclerosis: Secondary analysis of the WAVES trial.

Depression and anxiety are common psychiatric comorbidities among people with multiple sclerosis (MS). Emerging data suggest abnormal serum homocysteine, vitamin B12, and folate levels in people with MS, which are related to a range of neurological disorders, including mood and mental illnesses. Evidence suggests that dietary interventions could affect mood disorders via several pathways. This study aimed to evaluate the impact of the low-saturated fat (Swank) and modified Paleolithic elimination (Wahls) diets, along with a supplement regimen, on mood as assessed by Hospital Anxiety and Depression Scale (HADS), and Mental Health Inventory (MHI). The secondary objective was to identify changes in serum levels of homocysteine, folate, and vitamin B12 and the association and mediation effects between their changes and HADS and MHI scores and their subscales among people with relapsing-remitting MS (RRMS). In a previously conducted randomized parallel-arm trial, participants with RRMS (n=77) were randomly allocated to either the Swank or Wahls diets at baseline and followed for 24 weeks. Blood was drawn at four study visits spaced 12 weeks apart: (1) run-in, (2) baseline, (3) 12 weeks, and (4) 24 weeks. Serum vitamin B12, folate, and homocysteine were analyzed. HADS and MHI questionnaires were also completed by participants at the four study visits to assess symptoms of depression and anxiety, behavioral control and positive affect respectively. Significant improvement in severity of depression (HADS-D) and anxiety (HADS-A) symptoms, MHI total, and MHI subscores were seen at 12 and 24 weeks in each diet group. Further, a significant within-group reduction in serum homocysteine and a significant increase in serum vitamin B12 level were observed in both groups at 12 and 24 weeks compared to corresponding baseline values (p≤0.05 for all). All participants exceeded the analytical maximum threshold for folate of 20nmol/L at 12 and 24 weeks. Changes in serum levels of homocysteine and vitamin B12 were not associated with and did not mediate changes in HADS depression, anxiety, MHI total and four subscales scores (p>0.05). Participants on both Swank and Wahls dietary interventions, including folate and vitamin B12 supplements, showed significant improvement in mood. However, the favorable effects of both diets on mood were not associated with or mediated by the effect of the diets on serum levels of homocysteine, folate, and vitamin B12 (p>0.05).

A polyphenol-rich green Mediterranean diet enhances epigenetic regulatory potential: the DIRECT PLUS randomized controlled trial

BackgroundThe capacity of a polyphenol-enriched diet to modulate the epigenome in vivo is partly unknown. Given the beneficial metabolic effects of a Mediterranean (MED) diet enriched in polyphenols and reduced in red/processed meat (green-MED), as previously been proven by the 18-month DIRECT PLUS randomized controlled trial, we analyzed the effects of the green-MED diet on methylome and transcriptome levels to highlight molecular mechanisms underlying the observed metabolic improvements. MethodsOur study included 260 participants (baseline BMI = 31.2 kg/m2, age = 5 years) of the DIRECT PLUS trial, initially randomized to one of the intervention arms: A. healthy dietary guidelines (HDG), B. MED (440 mg polyphenols additionally provided by walnuts), C. green-MED (1240 mg polyphenols additionally provided by walnuts, green tea, and Mankai: green duckweed shake). Blood methylome and transcriptome of all study subjects were analyzed at baseline and after completing the 18-month intervention using Illumina EPIC and RNA sequencing technologies. ResultsA total of 1573 differentially methylated regions (DMRs; false discovery rate (FDR) < 5 %) were found in the green-MED compared to the MED (177) and HDG (377) diet participants. This corresponded to 1753 differentially expressed genes (DEGs; FDR < 5 %) in the green-MED intervention compared to MED (7) and HDG (738). Consistently, the highest number (6 %) of epigenetic modulating genes was transcriptionally changed in subjects participating in the green-MED intervention. Weighted cluster network analysis relating transcriptional and phenotype changes among participants subjected to the green-MED intervention identified candidate genes associated with serum-folic acid change (all P < 1 × 10−3) and highlighted one module including the KIR3DS1 locus, being negatively associated with the polyphenol changes (e.g. P < 1 × 10−4), but positively associated with the MRI-assessed superficial subcutaneous adipose area-, weight- and waist circumference- 18-month change (all P < 0.05). Among others, this module included the DMR gene Cystathionine Beta-Synthase, playing a major role in homocysteine reduction. ConclusionsThe green-MED high polyphenol diet, rich in green tea and Mankai, renders a high capacity to regulate an individual's epigenome. Our findings suggest epigenetic key drivers such as folate and green diet marker to mediate this capacity and indicate a direct effect of dietary polyphenols on the one‑carbon metabolism.

Oral Supplementation with Hydroxytyrosol Synthesized Using Genetically Modified Escherichia coli Strains and Essential Oils Mixture: A Pilot Study on the Safety and Biological Activity

Several natural compounds have been explored as immune-boosting, antioxidant and anti-inflammatory dietary supplements. Amongst them, hydroxytyrosol, a natural antioxidant found in olive products, and endemic medicinal plants have attracted the scientific community's and industry's interest. We investigated the safety and biological activity of a standardised supplement containing 10 mg of hydroxytyrosol synthesized using genetically modified Escherichia coli strains and equal amounts (8.33 μL) of essential oils from Origanum vulgare subsp. hirtum, Salvia fruticosa and Crithmum maritimum in an open-label, single-arm, prospective clinical study. The supplement was given to 12 healthy subjects, aged 26-52, once a day for 8 weeks. Fasting blood was collected at three-time points (weeks 0, 8 and follow-up at 12) for analysis, which included full blood count and biochemical determination of lipid profile, glucose homeostasis and liver function panel. Specific biomarkers, namely homocysteine, oxLDL, catalase and total glutathione (GSH) were also studied. The supplement induced a significant reduction in glucose, homocysteine and oxLDL levels and was tolerated by the subjects who reported no side effects. Cholesterol, triglyceride levels and liver enzymes remained unaffected except for LDH. These data indicate the supplement's safety and its potential health-beneficial effects against pathologic conditions linked to cardiovascular disease.

Cardiometabolic Risk Factors in Atorvastatin-Treated Women with Euthyroid Autoimmune Thyroiditis

Introduction: Autoimmune thyroiditis seems to be associated with increased cardiometabolic risk. Statins, the mainstay of cardiovascular risk reduction and prevention, were found to reduce thyroid antibody titers. The aim of this study was to investigate plasma markers of cardiometabolic risk in statin-treated women with thyroid autoimmunity. Methods: We compared two matched groups of euthyroid women with hypercholesterolemia receiving atorvastatin treatment: subjects with autoimmune (Hashimoto’s) thyroiditis (group A, n = 29) and subjects without thyroid pathology (group B, n = 29). Plasma lipids, glucose homeostasis markers, as well as circulating levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and 25-hydroxyvitamin D were measured before atorvastatin treatment and 6 months later. Results: At entry, both groups differed in antibody titers, insulin sensitivity, and plasma levels of uric acid, hsCRP, fibrinogen, homocysteine, and 25-hydroxyvitamin D. Atorvastatin-induced reduction in hsCRP and homocysteine, but not in total cholesterol and LDL-cholesterol, was more pronounced in group B than in group A. Only in group B, the drug decreased uric acid and fibrinogen and increased 25-hydroxyvitamin D. In group A, atorvastatin reduced insulin responsiveness. Conclusion: The obtained results indicate that euthyroid women with Hashimoto’s thyroiditis may benefit to a lesser degree from atorvastatin treatment than other populations of women with hypercholesterolemia.

Atherosclerosis and Endometriosis: The Role of Diet and Oxidative Stress in a Gender-Specific Disorder.

Background: Accelerated atherosclerosis in patients with endometriosis has been hypothesised, and lifestyle improvement might control cardiovascular risk. We explored cardiometabolic markers and oxidative stress and evaluated the effects of the Mediterranean Diet (MD) in modulating these markers. Methods: In this prospective study, we included 35 women with endometriosis. At baseline (T0) and after 3 (T1) and 6 (T2) months from the start of the diet, we investigated cardiometabolic parameters, lifestyle and oxidative stress. Results: After a 3-month intervention with MD, we observed a significant reduction in total cholesterol (p = 0.01) and LDL-c (p = 0.003). We observed at T1 an increase in B12 and E vitamins, folate and zinc. After 6 months, zinc (p = 0.04) and folate (p = 0.08) increased in comparison to T0. A reduction in homocysteine from T0 to T1 (p = 0.01) was found. After 3 months, an increase in Rapid Assessment of Physical Activity tool 1 (RAPA) (p < 0.001) and RAPA 2 was observed (p = 0.009). We observed high levels of oxidative stress markers at baseline. After 6 months of MD, a significant improvement in lymphocyte Reactive Oxygen Species (ROS) (p < 0.001) and total antioxidant capacity was observed (p = 0.02). Conclusions: The improvement of lifestyle, and in particular the Mediterranean dietary intervention, allowed the improvement of the metabolic and oxidative profile and overall health-related quality of life.

Homocysteine Reduction for Stroke Prevention: Regarding the Recent AHA/ASA 2021 Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack.

Reduction of secondary ischemic stroke risk following an initial stroke is an important goal. The 2021 Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack assembles opportunities for up to 80% secondary stroke reduction. Homocysteine reduction was not included in the recommendations. The reduction of homocysteine with low doses of folic acid has been shown to reduce ischemic stroke and all stroke. This has been obscured by studies using high doses of folic acid and cyanocobalamin in patients with renal failure and Methylenetetrahydrofolate reductase (MTHFR) polymorphisms. The confounding impacts of high dose folic acid and cyanocobalamin toxicity in renal failure and MTHFR C677T subgroups are discussed. New studies show that their toxicity is due to non-bioequivalence to the natural dietary forms, L-methylfolate and methylcobalamin. Low doses of folic acid and cyanocobalamin are safer than high doses for these subpopulations. Even lower toxicity with greater effectiveness for reducing homocysteine is seen with L-methylfolate and methylcobalamin, which are safe at high doses. Retinal vascular imaging is a noninvasive method for evaluating central nervous system (CNS) microangiopathy. A formulation containing l-methylfolate and methylcobalamin has been shown to reduce homocysteine and increase perfusion in diabetic retinopathy. This supports homocysteine intervention for CNS ischemia. Future ischemic stroke intervention studies could benefit from monitoring retinal perfusion to estimate the impact of risk reduction strategies. The omission of a recommendation for homocysteine and secondary stroke reduction through the use of B vitamins should be reconsidered in light of re-analysis of major B vitamin intervention studies and new technologies for monitoring CNS perfusion. We recommend revision of the 2021 Guideline to include homocysteine reduction with low doses of folic acid and cyanocobalamin, or better yet, L-methylfolate and methylcobalamin, making a good clinical guideline better.

Reduction of plasma homocysteine and 8-iso-prostaglandin F2α concentrations in hypercholesterolemic rats treated with clove essential oil

Cardiovascular diseases are associated with a chronic state of oxidative stress that is induced by fat accumulation. The current study aims to investigate the potential effects of oral consumption of clove essential oil on the lipid profile, oxidative stress markers and antioxidant enzyme activity, in hypercholesterolemic rats. Two groups of Wistar rats were fed a cholesterol-enriched diet supplemented (CEO) or not (HC) with 4 mg/kg b.w of clove essential oil, for six weeks. A control group (C) was fed a standard diet during the experiment. After six weeks, in clove essential oil treated as compared to untreated hypercholesterolemic rats, daily supplementation with essential oil attenuated serum levels of total cholesterol (-57%), LDL-cholesterol (-28%), triacyglycerols (-26%), total homocysteine (-17%) and 8-Iso-prostaglandin F2α (-39%). Furthermore, TBARS values were decreased in LDL (-37%), liver (-45%) and adipose tissue (-34%). Interestingly, clove essential oil increased respectively thioredoxin reductase activity in liver and adipose tissue by +67% and +66%, respectively. These results demonstrate the therapeutic potential of clove essential oil to reduce dyslipidemia, oxidative stress by increasing the thioredoxin reductase activity.

Prevalence of homocysteinemia and effect of vitamin supplementation in retinal vein occlusion

ObjectiveThe objective of this study was to determine the prevalence of homocysteinemia in patients with retinal vein occlusion (RVO). We investigated the association of B complex vitamin (BCV) and multivitamin...

Association Of the Methylene Tetrahydrofolate Reductase (MTHFR) Gene Polymorphism with Susceptibility to Recurrence of Cardiovascular Outcomes Among Ischemic Stroke- A Randomized Controlled Trial

Background: Hyperhomocystenemia and genetic variants are factors for causing young age stroke globally. This study aims to identify homocysteine related-MTHFR gene polymorphism that associated with recur-rent cardiovascular outcomes. Methodology: A randomized controlled trial conducted upon 90 hyperhomocysteinemic ischemic stroke patients were taken from the neurology wards of a tertiary care hospital were randomly selected into vita-min B therapy group and control groups (n=45 in each group). Baseline subject details were collected ve-nous blood sample for MTHFR genetic testing via PCR-RFLP technique along with blood homocysteine lev-els, vitamin B12, folic acid levels. Results: The results showed that the frequency of CT genotype polymorphism was 15.5% vs 13.3% for the MTHFR C677T gene without any significant difference between vitamin group and control group respective-ly (p-value &gt;0.05). The reduction in mean homocysteine up to -6.77±4.50 versus -2.08±0.71 µmol/L in the vitamin group as compared to control group respectively, p value 0.001. Conclusion: Considerable amount of MTHFR gene polymorphism found among hyperhomocysteinemic is-chemic stroke of sub-Himalayan region. Nutritional deficiencies including vitamin B 12 &amp; folic acid, and some hidden reasons found, which could lead to the primary cause of hyperhomocysteinemia. Vitamin B therapy is an effective for reducing homocysteine.

Mean platelet volume modifies the contribution of homocysteine to cardiovascular disease: A real-world study

Background and aimsThe effect of reductions in homocysteine (Hcy) on cardiovascular disease (CVD) was suggested to be modified by platelet activation, but the interaction between Hcy and platelet activation on CVD events is not well studied. Here, we aimed to examine the interaction between Hcy and platelet activation on CVD in a large, real-world population. Methods and resultsA total of 27,234 patients with hypertension (mean 63 years, 48% male) who were registered in Taicang city and free of CVD were prospectively followed up for new CVD events from 2017 to 2020. Hcy and platelet indices including mean platelet volume (MPV) were assayed at baseline. A total of 1063 CVD events were recorded during follow-up. Hcy at baseline was significantly associated with a higher risk of CVD (HR = 1.85, P < 0.001 for log-transformed Hcy). MPV showed a significant interaction effect with Hcy on CVD (HR = 1.20, P = 0.030 for the interaction term). The association between Hcy and CVD was significantly stronger in participants with a large (vs. small) MPV (HR = 2.71 vs. 1.32, P = 0.029 for log-transformed Hcy). For participants with both elevated Hcy and a large MPV, the attributable proportion of CVD events due to their interaction was 0.26 (95% CI: 0.06–0.45). ConclusionsThe association between Hcy and CVD was significantly stronger in patients with hypertension with a larger MPV. MPV may modify the contribution of Hcy to CVD events through synergistic interactions with Hcy. These findings suggest that MPV could be monitored and controlled in the prevention of CVD.

Responsiveness of one-carbon metabolites to a high-protein diet in older men: Results from a 10-wk randomized controlled trial

ObjectivesDietary strategies to promote successful aging are divergent. Higher-protein diets are recommended to preserve skeletal muscle mass and physical function. Conversely, increased B-vitamin intake, supporting one-carbon (1C) metabolism, reduces the risk of cognitive decline and cardiovascular disease. On the hypothesis that higher protein intake through animal-based sources will benefit 1C regulation by the supply of B vitamins (folate, riboflavin, and vitamins B6 and B12) and methyl donors (choline) despite higher methionine intake, this study explored the effect of a higher-protein diet on 1C metabolite status in older men compared to current protein recommendations. MethodsOlder men (age, 74 ± 3 y) were randomized to receive a diet for 10 wk containing either the recommended dietary allowance (RDA) of protein (0.8 g/kg body weight/d, n = 14), or double that amount (2RDA, n = 15), with differences in protein accounted for by modifying carbohydrate intake. Intervention diets were matched to each individual's energy requirements based on the Harris–Benedict equation and adjusted fortnightly as required depending on physical activity and satiety. Fasting plasma 1C metabolite concentrations were quantified by liquid chromatography coupled with mass spectrometry at baseline and after 10 wk of intervention. ResultsPlasma homocysteine concentrations were reduced from baseline to follow-up with both diets. Changes in metabolite ratios reflective of betaine-dependent homocysteine remethylation were specific to the RDA diet, with an increase in the betaine-to-choline ratio and a decrease in the dimethylglycine-to-betaine ratio. Comparatively, increasing folate intake was positively associated with a change in choline concentration and inversely with the betaine-to-choline ratio for the 2RDA group. ConclusionsAdding to the known benefits of higher protein intake in older people, this study supports a reduction of homocysteine with increased consumption of animal-based protein, although the health effects of differential response of choline metabolites to a higher-protein diet remain uncertain.

Randomised Controlled Trial of Nutritional Supplement on Bone Turnover Markers in Indian Premenopausal Women.

Young Indian women may be at risk of poor bone health due to malnutrition. The aim of this study was to examine the effects on bone metabolism of a nutritional supplement in women aged 25 to 44. The nutritional supplement was a protein-rich beverage powder fortified with multi-micronutrients including calcium (600 mg), vitamin D (400 IU), and vitamin K (55 mcg) per daily serving, while a placebo supplement was low-protein non-fortified isocaloric beverage powder. This 6-month randomised, controlled trial showed favorable changes in bone turnover markers (decreased) and calcium homeostasis; such changes in older adults have been associated with slowing of bone loss and reduced fracture risk. For example, serum CTX decreased by about 30% and PINP by about 20% as a result of the increase in calcium intake. There were also changes in the ratio of carboxylated to undercarboxylated osteocalcin and such changes have been linked to a slowing of bone loss in older subjects. For example, the ratio increased by about 60% after 3 months as a result in the improvement in vitamin K status. Finally, there were improvements in the status of B vitamins, and such changes have been associated with reductions in homocysteine, but it is uncertain whether this would affect fracture risk. The product was generally well tolerated. This study shows the nutritional supplement holds promise for improved bone health among young Indian women.

The effect of feeding adequate or deficient vitamin B6 or folic acid to breeders on methionine metabolism in 18-day-old chick embryos

Three isotopic tracers ([2,3,3-2H3]-L-serine, [2H11]-L-betaine, and [1-13C]-L-methionine) were administered by amnion injection into 18-day-old chick embryos to investigate the kinetics of methionine metabolism. The embryos utilized were from eggs collected from 34-week-old Cobb 500 broiler breeders that were fed either a control diet containing folic acid (1.25 mg/kg diet) and pyridoxine HCl (5 mg/kg diet) or diets devoid of supplemental pyridoxine or folic acid. Intermediate metabolites of methionine metabolism and polyamines were analyzed in 18-day-old chick embryos. There were no differences in hepatic [2H2] methionine or [2H3] cysteine enrichments or in physiological concentrations of sulfur amino acids for chick embryos from breeders fed the control diet and embryos from breeders fed diets containing no pyridoxine or folic acid. Supplementation of B6 or folic acid did not affect the production of methionine and cysteine in chick embryos. However, breeders fed the control diet with both folic acid and pyridoxine supplementation produced embryos with a two-fold reduction of hepatic homocysteine and increased spermine compared with embryos from breeders fed diets containing no supplemental pyridoxine or folic acid (P < 0.05). Hepatic S-adenosylmethionine for embryos from breeders fed no supplemental B6 was half the concentration compared with embryos from breeders fed the control diet. Embryos from breeders fed the control diet were utilized to determine the proportion of homocysteine going through remethylation and transsulfuration and also to determine the pathway of remethylation. Sixty-five percent of the methyl groups used for homocysteine remethylation from control embryos was via the MFMT pathway. Alternatively, 61% of homocysteine from control embryos was remethylated via the MFMT and the BHMT reactions and 39% of homocysteine was catabolized to cysteine via the transsulfuration pathway. These data show that in embryos, intermediate metabolites of methionine and polyamines increase in concentration when pyridoxine levels are provided in deficient concentrations to the breeder hen. In addition, this research demonstrates that folic acid deficient embryos conserve methionine, rather than catabolize it to cysteine.

Adapted recreational football small-sided games improve cardiac capacity, body composition and muscular fitness in patients with type 2 diabetes.

The usefulness of adapted small-sided games (SSGs) in improving cardiac function in subjects with T2DM is still debated. Here we evaluated the effects of 18 weeks indoor muscular activation training (6 weeks; IMA) followed by adapted SSGs football training (12 weeks) on cardiac function, muscular fitness, body composition and adiponectin expression in sedentary T2DM volunteers. Six T2DM patients underwent IMA protocol of 6 weeks, twice a week followed by 12 weeks SSGs (5-a-side, once a week) training. Glucose, lipid profile and serum homocysteine concentration, body composition (BC), bone mineral density (DEXA), were determined at baseline and after 18 weeks (IMA+SSGs). VO<inf>2max</inf> and muscular fitness were recorded at baseline and after IMA (6 weeks) and SSGs (12 weeks), respectively. No significant differences were found for VO<inf>2max</inf> and muscular fitness after 6weeks of IMA. After 18 weeks (6 weeks IMA + 12 weeks SSGs) of training, significant improvements were found in the following parameters: work capacity, VO<inf>2peak</inf>, Ventilation (VE<inf>peak</inf>), breathing reserve consumption and oxygen uptake efficiency slope (P<0.05); leg fitness (P<0.05), BC (P<0.05), vertebral column T-score (P<0.01) and adiponectin (total and high-molecular-weight; P<0.05). Compared to baseline, a reduction in serum homocysteine occurred after 18 weeks of training (P<0.05). We evidenced that weekly adapted SSGs friendly football matches for 12 weeks improve cardiorespiratory capacity and the expression of independent markers associated with cardiovascular risk in T2DM patients, suggesting an overall reduced CVD-risk in these patients. These preliminary data encourage us to test the efficacy of this type of exercise in a larger population.

A prospective cohort study of MTHFR C677T gene polymorphism and its influence on the therapeutic effect of homocysteine in stroke patients with hyperhomocysteinemia

BackgroundHyperhomocysteinemia (HHCY) is a risk factor for cardiovascular and cerebrovascular diseases. The C677T 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism increases homocysteine (HCY) levels. This study analyzed the relationship between C677T MTHFR polymorphism and the therapeutic effect of lowering HCY in stroke patients with HHCY.MethodsBaseline data were collected from stroke patients with HHCY for this prospective cohort study. The C677T MTHFR genotype was detected by polymerase chain reaction-restriction fragment length polymorphism and the therapeutic effect to reduce HCY was compared.ResultsOf 200 stroke patients 162 (81.0%) completed follow-up and were evaluated. Most of them responded well to treatment (103 cases, 63.5%), but 59 (36.4%) patients were in the poor efficacy group. There was a significant difference in terms of age (P < 0.001), hypertension (P = 0.041), hyperuricemia (P = 0.042), HCY after treatment (P < 0.001), and MTHFR genotype (P < 0.001) between the poor efficacy and effective groups, with increased frequency of the TT genotype in the poor efficacy group. Logistic regression showed that the T allele was associated with poor efficacy (OR = 0.733, 95%CI: 0.693, 0.862, P < 0.001). In the codominant model the TT genotype was associated with poor outcome (OR = 0.862, 95%CI: 0.767, 0.970, P = 0.017) and this was also the case in the recessive model (OR = 0.585, 95%CI: 0.462, 0.741, P < 0.001) but there was no association between CT and TT in the dominant model.ConclusionsThe T allele and TT genotype of the MTHFR C677T polymorphism was associated with poor HCY reduction treatment efficacy in stroke patients with HHCY.Trial registrationThe registration number of the clinical trial is ChiCTR1800020048. Registration date: December 12, 2018.