Association of methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms with serum folate, cobalanin and homocysteine concentrations in Greek adults.

Methylene tetrahydrofolate reductase (MTHFR) is a key enzyme of homocysteine metabolism participating in the folate cycle. The aim of this study was to investigate the association of MTHFR C677T and MTHFR A1298C gene polymorphisms with serum folate, cobalamin (Cbl) and homocysteine (Hcy) concentrations in healthy Greek adults. The MTHFR C677T and A1298C gene polymorphisms were genotyped in 383 healthy Greek adults (199 men and 184 women) using polymerase chain reaction and reverse hybridization. Serum folate, Cbl and total Hcy (tHcy) levels were determined using immunoassays methods. Among the 383 individuals, 73 (19.1%) were normal (CC), 202 (52.7%) were heterozygous (CT) and 108 (28.2%) were homozygous (TT) regarding the MTHFR C677T gene polymorphism, while 263 (68.7%) were normal (AA), 105 (27.4%) were heterozygous (AC) and 15 (3.9%) were homozygous (CC) regarding the MTHFR A1298C gene polymorphism. The overall C and T allele frequency for the MTHFR C677T gene polymorphism was 45.4% and 54.6%, respectively, while the overall A and C allele frequency for the MTHFR A1298C gene polymorphism was 82.3% and 17.6%, respectively. The MTHFR C677T and not the A1298C gene polymorphism had a significantly influence on serum folate and tHcy levels. The individuals with 677TT genotype had significantly lower serum folate and significantly higher serum tHcy levels than individuals with 677 CC or CT genotypes. Serum folate and tHcy levels are influenced by the existence of the MTHFR C677T gene polymorphism (mainly 677TT genotype). Individuals with low serum folate levels and/or high serum tHcy levels should be further investigated for a possible existence of MTHFR C677T and not A1298C gene polymorphisms, with aim to determine the suitable treatment.

A Patient with Dysphagia.

We report a case of an uncommon type of dysphagia, due to esophagus compression by an aberrant right subclavian artery. This condition, known as dysphagia lusoria, was first recorded in 1787 by London physician David Bayford.

Differentiated thyroid cancer and selenium supplements for protection of salivary glands from 131I treatment.

Dear Editor, I read with great interest the article by Son et al about the radioprotective effect of selenium (Se) supplementation for the salivary glands from 131I treatment in patients with differentiated thyroid cancer (DTC). In this study, 8 patients received 300µg of Se (as inorganic sodium selenite; selenase®) orally for 10 days, 3 days before to 6 days after 131I treatment. On the occasion of the use of Se among these patients, I want with this letter to remind the differences among the prescribed Se supplements in clinical practice, such as the possible health consequences of Brazil nut consumption as another choice for the preparation of DTC patients for radioactive iodine (RAI) therapy. Selenium is an essential element with many pleiotropic effects that can be found in foods and supplements in organic form (as selenomethionine, selenocysteine, γ-glutamyl-Se-methylselenocysteine) or/and in inorganic form (as sodium selenate and sodium selenite). Selenium in multivitamin/multimineral supplements or in a stand-alone supplement is often available in the forms of L-selenomethionine, Se-enriched yeast (grown in a high-Se medium), mustard seed-derived Se, or as sodium selenite or sodium selenate. Because these two (organic and inorganic) forms of Se are absorbed and metabolized differently, it is very important for the physicians, when prescribe a Se supplement, to know the contained form of Se. Inorganic forms of Se are easily absorbed through the intestine but poorly retained. Once they reach the blood, inorganic Se is quickly filtered out by the kidneys and excreted in the urine. So, the consumption of supplements with inorganic forms of Se does not offer the maximum health benefits of the element. Conversely, Se-containing amino acids, such as selenomethionine and selenocysteine, are introduced directly into proteins, including muscle proteins. These organic proteins-bound Se (selenoproteins) are better retained, utilized, and incorporated by the human body. About 90% of the received selenomethionine is actually absorbed in the intestinal tract, and about half of that remains in the body. The higher degree of absorption of selenomethionine against selenite was described in a recently published systematic review and meta-analysis by Wichman et al. In this review, a significant decrease in serum thyroid peroxidase antibodies (TPO-Ab) levels was found among patients receiving 200µg selenomethionine, but not among those receiving 200µg sodium selenite. In another investigation, 10 groups of Se-replete subjects were randomly assigned to receive a placebo or either 200 or 400 or 600µg/day Se as selenomethionine, sodium selenite, or high-selenium yeast (in which an estimated 75% of Se was in the form of selenomethionine) for 16 weeks. Selenium bioavailability, based on urinary excretion, was greatest for selenomethionine and lowest for selenite. However, supplementation with any of these forms only affected plasma Se levels and not glutathione peroxidase activity or selenoprotein P concentration, suggesting that study participants were selenium replete before they began taking Se supplements. Because the absorption of selenite was approximately two-thirds of the absorption of selenomethionine in this study, we can assume that the daily dose of 300µg of sodium selenite in the study of Son et al corresponded to 200µg of selenomethionine which is the most frequently used dose in intervention trials. However, in our opinion, the prescription of supplements with organic forms of Se must be preferred, when required. It is also worth mentioning that the prescribed Se supplements should not contain iodine considering that for a successful RAI therapy after thyroidectomy, DTC patients must, not only increase their thyroid-stimulating hormone (TSH) levels, but also deplete the whole body iodine pool through a low-iodine diet (low-quality evidence). One of the richest known food sources of bioavailable Se, in the organic form of selenomethionine, are the Brazil nuts. Brazil nuts grow on massive tropical trees, the Bertholletia excelsa of the Lecythidaceae family, some reaching heights over 45m. The average Se content of each Brazil nut in most elemental analyses varies ranging from 2.7 to 11µg Se/g, and the average weight of each nut varies between 3 and 4 g. Their consumption can increase the likelihood of Se toxicity, regardless of the quantity of the nuts consumed, and thus is not be a safe dietary choice. Moreover, Brazil nuts may be infected externally by aflatoxins or can trigger allergic reactions in sensitive people. However, raw Brazil nuts don't contain iodine and thus their consumption would not undermine the dietary efforts of DTC patient in the framework of the required low-iodine diet. The consumption of 2-3 unshelled and raw (unsalted) Brazil nuts daily could be another choice for the post-thyroidectomy period up to 10 days after RAI therapy among DTC patients who do not want to receive supplements as source of Se. We must emphasize that some patients having DTC and also Hashimoto's thyroiditis may had previously received Se supplements or Brazil nuts for a long period of time before DTC was diagnosed and thyroidectomy had followed. In conclusion, the prescription of supplements with organic forms of Se must be preferred against of supplements with inorganic forms of Se among DTC patients for the protection of their salivary glands from 131I treatment and Brazil nuts could be another choice.

A concise review of Hashimoto thyroiditis (HT) and the importance of iodine, selenium, vitamin D and gluten on the autoimmunity and dietary management of HT patients.Points that need more investigation.

Hashimoto's thyroiditis (HT) is a chronic autoimmune thyroid disease caused by an interaction between genetic factors and environmental conditions, both of which are yet to be fully understood. The management of HT depends on its clinical manifestations, commonly including diffuse or nodular goiter with euthyroidism, subclinical hypothyroidism and permanent hypothyroidism. However, in most cases of patients with HT, lifelong levothyroxine substitution is required. The additional role of diet for the management of HT is usually overlooked. A literature search regarding the importance and the influence of iodine, selenium, vitamin D and gluten on HT was conducted. In HT careful supplementation of possible deficiencies is recommended for the dietary management of these patients. The use of a diet low in gluten among HT patients with or without celiac disease (CD) is discussed.

Primary and secondary hyperparathyroidism among vitamin D deficient Hashimoto's thyroiditis patients and the need for a parathyroid scan.

The patients with Hashimoto thyroiditis must be investigated mainly for secondary hyperparathyroidism due to vitamin D deficiency/insufficiency. Parathyroid scintigraphy has no place in the diagnosis of primary, secondary or tertiary hyperparathyroidism or in the decision for surgical treatment. Parathyroid scintigraphy is a useful preoperative technique for the localization of the pathological parathyroid glands.

Is vitamin D related to pathogenesis and treatment of Hashimoto's thyroiditis?

OBJECTIVE: The aim of this study was to investigate vitamin D status by measuring serum 25(OH)D levels in euthyroid patients with Hashimoto's thyroiditis (HT) who lived and worked on the sunny island of Crete, Greece, and to evaluate whether vitamin D3 supplementation is beneficial for the management of HT patients with vitamin D deficiency. SUBJECTS AND METHODS: We studied 218 HT patients, euthyroid Caucasian Cretan Greek citizens: 180 females and 38 males. Among these patients, 186 (85.3%) had vitamin D deficiency defined as serum 25(OH)D levels < 30 ng/mL. The mean age of all these 218 HT patients was 35.3 ± 8.5 years. The mean age of the 186 vitamin D deficient HT patients (173 females and 13 males) was 37.3 ± 5.6 years. The 186 vitamin D deficient HT patients received vitamin D3 (cholecalciferol, CF) orally, 1200-4000 IU, every day for 4 months aiming to maintain serum 25(OH)D levels ≥ 40 ng/mL. Anthropometric characteristics (height, weight, waist circumference), systolic and diastolic blood pressure, serum concentration of 25(OH)D, thyrotropin (TSH), free thyroxine (FT4), anti-thyroid peroxidase (anti-TPO), antithyroglobulin (anti-TG), calcium and phosphorus levels and thyroid and kidney sonographic findings were recorded and measured before and after CF administration. RESULTS: There was a significant negative correlation only between serum 25(OH)D levels and anti-TPO levels among all 218 HT patients. Also, anti-TPO levels were significantly higher in 186/218 vitamin D deficient HT patients compared to 32/218 HT patients with no vitamin D deficiency (364 ± 181IU/mL versus 115.8 ± 37.1IU/mL, P<0.0001). Supplementation of CF in 186 vitamin D deficient HT patients caused a significant decrease (20.3%) in serum anti-TPO levels. Although at the end of the 4 months period of the study body mass index (BMI), serum anti-TG and TSH levels decreased by 2.2%, 5.3% and 4% respectively, these differences were not significant. No changes in the sonographic findings were observed. CONCLUSION: The majority (85.3%) of the Greek Caucasian patients with HT studied who lived and worked in Crete had low serum 25(OH)D levels inversely correlated with serum anti-TPO thyroid antibodies. After 4 months of CF supplementation in the 186 HT patients with vitamin D deficiency, a significant decrease (20.3%) of serum anti-TPO levels was found. These findings suggest that vitamin D deficiency may be related to pathogenesis of HT and that its supplementation could contribute to the treatment of patients with HT.

The hypolipidaemic effects of Spirulina (Arthrospira platensis) supplementation in a Cretan population: a prospective study.

BACKGROUND: Spirulina (Arthrospira platensis) is a filamentous cyanobacterium used as a food supplement. The objective of the study was to determine the lipid-lowering effects of Spirulina in Cretan Greek dyslipidaemic patients, and to document its effectiveness as a possible alternative treatment for dyslipidaemia. Fifty-two adultCretan outpatients (32 men, 20 women), median age 47 (range, 37-61) years, with recently diagnosed dyslipidaemia, consumed orally 1 g Spirulina (Greek production) per day for 12 weeks. The full lipid profile was measured in fasting blood samples at the beginning and end of the study period. Anthropometric measurements including systolic and diastolic blood pressure, height, weight and body mass index were also recorded. RESULTS: At the end of the 3-month intervention period the mean levels of triglycerides, low density lipoprotein-cholesterol, total cholesterol, non-high density lipoprotein-cholesterol levels, and the ratio of total cholesterol to high-density lipoproteincholesterol were significantly decreased: 16.3% (P < 0.0001), 10.1% (P < 0.0001), 8.9% (P < 0.0001), 10.8% (P < 0.0001) and 11.5% (P = 0.0006) respectively, whereas the mean high-density lipoprotein-cholesterol levels were not significantly increased (3.5%). Blood pressure, weight and body mass index remained almost unchanged. CONCLUSIONS: Spirulina supplementation at a dose of 1 g daily has powerful hypolipidaemic effects, especially on the triglyceride concentration in dyslipidaemic Cretan outpatients.

Hashimoto's autoimmune thyroiditis and vitamin D deficiency. Current aspects.

Hashimoto's thyroiditis (HT) is a chronic autoimmune thyroid disease caused by an interaction between genetic factors and environmental conditions, both of which are not yet completely understood. The significant association between vitamin D deficiency and HT has been investigated regarding the immune role of this hormone. In HT, an immunologic reaction is triggered when thyrocytes express major histocompatibility complex (MHC) class II surface HLA-DR antigens, a process induced by the production from T helper (Th)1 type lymphocytes, of inflammatory cytokines (especially IFN-γ), which may be inhibited by 1,25[OH]2D. Genetic polymorphism of vitamin D receptor (VDR), binding protein (DBP) and of 1α-hydroxylase (CYP1α) may also predispose to the development of HT. Considering current evidence, presented in this review, screening for vitamin D deficiency and careful vitamin D supplementation, when required, may be recommended for patients with HT. Further research is needed in patients with HT in order to investigate the mechanisms by which vitamin D affects autoimmunity and also to evaluate the cost-effectiveness of vitamin D supplementation and to suggest the possible optimal dose treatment.

Associations of serum 25-hydroxyvitamin D with serum folate, cobalanin, and homocysteine concentrations and methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in healthy adults.

AIM: The aim of this study was to investigate the associations of serum 25-hydroxyvitamin D [25(OH)D] with various demographic, anthropometric, and genetic characteristics and biochemical parameters in healthy Greek adults. METHODS: Demographic (age and sex), anthropometric (body mass index/BMI), and genetic (MTHFR gene polymorphisms) characteristics and biochemical parameters (serum folate, cobalamin/Cbl, and total homocysteine/tHcy concentrations), which had been recorded and measured, among others, in the framework of periodic medical examination (military personnel) or check-up (non-military personnel) of 383 healthy Greek adults (199 men and 184 women) were analyzed. Serum 25(OH)D, tHcy, folate, and Cbl levels were determined using immunoassay methods. The MTHFR C677T and A1298C gene polymorphisms were genotyped using polymerase chain reaction and reverse hybridization. RESULTS: Serum 25(OH)D concentrations were correlated with Cbl levels and MTHFR C677T gene polymorphism, while they had a reverse correlation with serum tHcy levels, age, and BMI. There was no significant correlation between serum 25(OH)D concentrations and sex, serum folate levels, and smoking status. Individuals with the 677TT genotype had statistically significantly lower serum 25(OH)D levels than those with the 677CC or 677CT genotype, while individuals with the 1298CC genotype had statistically significantly higher serum 25(OH)D levels than those with 1298AA or 1298AC genotype. Moreover, the reverse correlation between the serum 25(OH)D and tHcy levels was statistically significant in all six MTHFR genotypes. CONCLUSIONS: Serum 25(OH)D levels are associated with age, BMI, serum tHcy, and Cbl levels and MTHFR C677T gene polymorphism. The most significant finding of our study is the observed reverse correlation of serum 25(OH)D levels with serum tHcy levels. Considering that vitamin D deficiency and hyperhomocysteinemia (HHcy) are associated with an increased risk for cardiovascular diseases (CVDs), we suggest that individuals with high serum tHcy levels should be further investigated for, inter alia, their serum 25(OH)D levels.

Associations of Serum Total Homocysteine Levels with Various Demographic, Clinical and Genetic Characteristics in Healthy Greek Adults.

AIM: The aim of this study was to investigate the association of serum total Hcy (tHcy) levels with various demographic, clinical and genetic characteristics in healthy Greek adults. METHODS: Anthropometric characteristics (height, weight), systolic and diastolic blood pressure, complete blood count and biochemical assessments, were recorded and measured among 383 Greek adults (199 men). Serum folate, Cobalamin (Cbl) and tHcy levels were determined using immunoassays methods. The MTHFR C677T and A1298C gene polymorphisms were genotyped using polymerase chain reaction and reverse hybridization. RESULTS: MTHFR C677T gene polymorphism, serum folate and Cbl levels were correlated with serum tHcy levels independently. The individuals with 677TT genotype had significantly higher serum tHcy levels than individuals with 677 CC or CT genotypes. Regarding the MTHFR C677T gene polymorphism, the existence of the T allele was associated with statistically significantly lower serum folate and higher serum tHcy levels than C allele. Regarding the MTHFR A1298C gene polymorphism, the existence of the C allele was associated with statistically significant lower serum tHcy levels than A allele. Furthermore, there was no significant correlation between the serum tHcy levels and demographic (except age) or clinical characteristics (sex, BMI, smoking status, SBP, DBP, HGB, HCT, TC, TG, HDL-C, LDL-C, TC/HDL-C). CONCLUSIONS: Serum tHcy levels are influenced by the existence of MTHFR C677T gene polymorphism (mainly 677TT genotype), serum folate and Cbl levels. Individuals with hyperhomocysteinemia should be further investigated for the existence of MTHFR C677T gene polymorphism, with the aim to determine the suitable treatment.

The effects of folinic acid and l-methylfolate supplementation on serum total homocysteine levels in healthy adults.

BACKGROUND - AIM: Hyperhomocysteinemia is recognized as a risk factor for several diseases and conditions. The aim of this study was to investigate and compare the efficacy of two total homocysteine (tHcy)-lowering treatments including folinic acid or l-methylfolate in healthy Greek adults. METHODS: Two hundred and seventy-two healthy Greek adults (143 men, 129 women; mean age±SD: 43.0 ± 15.3 years), with serum tHcy levels ≥10 µmol/L received randomized folinic acid ("Folinic acid Group") or l-methylfolate ("l-methylfolate Group") orally for three months. All subjects with serum cobalamin (Cbl) levels <300 pg/mL additionally received 1 mg hydroxycobalamine intramuscularly twice a week for the first month only. Serum folate, Cbl and tHcy levels were determined using immunoassays methods at the beginning and the end of the study period. The MTHFR C677T and MTHFR A1298C gene polymorphisms were genotyped using polymerase chain reaction and reverse hybridization. RESULTS: At the end of the 3-month intervention period, the levels of serum folate and Cbl increased significantly, whereas the levels of serum tHcy decreased significantly in the two groups. The individuals with MTHFR 677TT genotype had a significantly higher reduction in serum tHcy levels than the individuals with the MTHFR 677CC or MTHFR 677CT genotypes. Although the "Folinic acid Group" had a considerably higher increase in their serum folate levels (but not Cbl) than the "l-methylfolate Group", the reduction of serum tHcy levels between the two groups was not substantially different. The individuals with MTHFR 677CT genotype had a statistically significant higher reduction in serum tHcy levels when supplemented with folinic acid rather than l-methylfolate. CONCLUSIONS: The administration of folinic acid compared to l-methylfolate caused a higher increase of serum folate levels but no difference in the reduction of serum tHcy levels. The reduction of serum tHcy levels was influenced by the existence of MTHFR C677T and not MTHFR A1298C gene polymorphisms. The individuals with MTHFR 677CT genotype appear to benefit more by folinic acid than l-methylfolate supplementation.

Improvement of ulcerative pyoderma gangrenosum with hyperbaric oxygen therapy.

Pyoderma gangrenosum (PG) is a rare noninfectious destructive neutrophilic dermatosis of unknown origin affecting the skin and occasionally the subcutaneous fat. In this report, we present the results of intensive hyperbaric oxygen (HBO) therapy in a 62-year-old Greek woman who had been diagnosed with ulcerative PG two years ago, but had been resistant to other therapies.