Beyond Seasoning-The Role of Herbs and Spices in Rheumatic Diseases.

Although we have witnessed remarkable progress in understanding the biological mechanisms that lead to the development of rheumatic diseases (RDs), remission is still not achieved in a substantial proportion of patients with the available pharmacological treatment. As a consequence, patients are increasingly looking for complementary adjuvant therapies, including dietary interventions. Herbs and spices have a long historical use, across various cultures worldwide, for both culinary and medicinal purposes. The interest in herbs and spices, beyond their seasoning properties, has dramatically grown in many immune-mediated diseases, including in RDs. Increasing evidence highlights their richness in bioactive molecules, such as sulfur-containing compounds, tannins, alkaloids, phenolic diterpenes, and vitamins, as well as their antioxidant, anti-inflammatory, antitumorigenic, and anticarcinogenic properties. Cinnamon, garlic, ginger, turmeric, and saffron are the most popular spices used in RDs and will be explored throughout this manuscript. With this paper, we intend to provide an updated review of the mechanisms whereby herbs and spices may be of interest in RDs, including through gut microbiota modulation, as well as summarize human studies investigating their effects in Rheumatoid Arthritis, Osteoarthritis, and Fibromyalgia.

The Mediterranean diet, and not dietary inflammatory index, is associated with rheumatoid arthritis disease activity, the impact of disease and functional disability.

PURPOSE: To assess the relationship between adherence to the Mediterranean Diet (MD) /individual Dietary Inflammatory Index (DII) and disease activity, disease impact, and functional status in Rheumatoid Arthritis (RA) patients. METHODS: RA patients followed at a hospital in Lisbon, Portugal, were recruited. DII was calculated using dietary intake data collected with a food frequency questionnaire (FFQ). Adherence to the MD was obtained using the 14-item Mediterranean Diet assessment tool. Disease Activity Score of 28 Joints (DAS28) and the DAS28 calculated with C-Reactive Protein (DAS28-CRP) were used to assess disease activity. Impact of disease and functional status were evaluated using the Rheumatoid Arthritis Impact of Disease (RAID) questionnaire and the Health Assessment Questionnaire (HAQ), respectively. RESULTS: 120 patients (73.3% female, 61.8 ± 10.1 years of age) were included. Patients with higher adherence to the MD had significantly lower DAS28-CRP (median 3.27(2.37) vs 2.77(1.49), p = 0.030), RAID (median 5.65(2.38) vs 3.51(4.51), p = 0.032) and HAQ (median 1.00(0.56) vs 0.56(1.03), p = 0.013) scores. Higher adherence to the MD reduced the odds of having a higher DAS28 by 70% (OR = 0.303, 95%CI = (0.261, 0.347), p = 0.003). Lower adherence to MD was associated with higher DAS28-CRP (ß = - 0.164, p = 0.001), higher RAID (ß = - 0.311, p < 0.0001), and higher HAQ scores (ß = - 0.089, p = 0.001), irrespective of age, gender, BMI and pharmacological therapy. Mean DII of our cohort was not significantly different from the Portuguese population (0.00 ± 0.17 vs - 0.10 ± 1.46, p = 0.578). No associations between macronutrient intake or DII and RA outcomes were found. CONCLUSIONS: Higher adherence to the MD was associated with lower disease activity, lower impact of disease, and lower functional disability in RA patients.

Mediterranean Diet: A Dietary Pattern Related to Nutritional Benefits for Hemodialysis Patients.

OBJECTIVES: In adults with chronic kidney disease, not on dialysis, there is a recent recommendation suggesting the prescription of a Mediterranean diet pattern but there is still no evidence to suggest a specific dietary pattern for hemodialysis (HD) patients. The aim of this study was to identify dietary patterns in HD patients and analyze their relationship with nutritional status, physical activity, and survival. DESIGN AND METHODS: This was a longitudinal prospective multicenter study with 12 months of follow-up that included 582 HD patients from 37 dialysis centers. Clinical parameters, dietary intake, and physical activity were assessed. Dietary patterns were derived from principal component analysis. A p-value lower than 0.05 was considered statistically significant. RESULTS: Three different dietary patterns were identified: "Mediterranean," "Western," and "low animal protein." Patients in the Mediterranean pattern group showed higher intakes of protein (P = .040), omega 3 fatty acids (P < .001), vitamins B12 (P < .001), B6 (P < .001), C (P < .001), D (P < .001), folic acid (P < .001) and presented a higher practice of moderate physical activity (P = .010). Despite the lower number of deaths that occurred in the Mediterranean dietary pattern group, we did not observe a statistically significant lower mortality risk (P = .096). CONCLUSIONS: The Mediterranean style pattern was associated with a better nutritional intake profile and lifestyle related factors such as a higher practice of moderate physical activity in HD patients.

Nutritional Genomics in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a common chronic condition associated with genetic and environmental factors in which fat abnormally accumulates in the liver. NAFLD is epidemiologically associated with obesity, type 2 diabetes, and dyslipidemia. Environmental factors, such as physical inactivity and an unbalanced diet, interact with genetic factors, such as epigenetic mechanisms and polymorphisms for the genesis and development of the condition. Different genetic polymorphisms seem to be involved in this context, including variants in PNPLA3, TM6SF2, PEMT, and CHDH genes, playing a role in the disease's susceptibility, development, and severity. From carbohydrate intake and weight loss to omega-3 supplementation and caloric restriction, different dietary and nutritional factors appear to be involved in controlling the onset and progression of NAFLD conditions influencing metabolism, gene, and protein expression. The polygenic risk score represents a sum of trait-associated alleles carried by an individual and seems to be associated with NAFLD outcomes depending on the dietary context. Understanding the exact extent to which lifestyle interventions and genetic predispositions can play a role in the prevention and management of NAFLD can be crucial for the establishment of a personalized and integrative approach to patients.

Probiotic Supplementation for Rheumatoid Arthritis: A Promising Adjuvant Therapy in the Gut Microbiome Era.

Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease that ultimately leads to joint destruction and functional disability. Although the exact etiology of RA is not fully understood, it is well established that gut microbiota (GM) plays a vital role in the pathogenesis of RA, with accumulating evidence suggesting that gut dysbiosis induces a chronic inflammatory response that may be linked to disease development. Of interest, patients with RA have significant changes in the intestinal microbiota compared to healthy controls, and several studies have suggested the use of probiotics as a possible adjuvant therapy for RA. Benefits of probiotic supplementation were reported in animal models of arthritis and human studies, but the current evidence regarding the effect of probiotic supplementation in the management of RA remains insufficient to make definite recommendations. Several different strains of Lactobacillus and Bifidobacteria, as single species or in mixed culture, have been investigated, and some have demonstrated beneficial effects on disease activity in RA human subjects. As of now, L.casei probiotic bacteria seems to be the strongest candidate for application as adjuvant therapy for RA patients. In this review, we highlight the role of GM in the development and progression of RA and summarize the current knowledge on the use of probiotics as a potential adjuvant therapy for RA. We also review the proposed mechanisms whereby probiotics regulate inflammation. Finally, the role of fermented foods is discussed as a possible alternative to probiotic supplements since they have also been reported to have health benefits.

The validity of the Patient-Generated Subjective Global Assessment Short-form© in cancer patients undergoing chemotherapy.

BACKGROUND & AIMS: The high prevalence of malnourished cancer patients highlights the importance of sensitive and specific tools for nutritional risk and status assessment screening, namely the Patient-Generated Subjective Global Assessment (PG-SGA®). This study aimed to assess whether the short-form version of the PG-SGA® (PG-SGA© SF) would be appropriate to identify the nutritional risk of patients when compared with the final global score of PG-SGA© (long-form version). METHODS: This transversal and observational study comprised a convenience sample of cancer patients undergoing chemotherapy at the Champalimaud Clinical Centre between December 2016 and February 2018. Clinical data and anthropometric parameters were collected in order to apply PG-SGA® and PG-SGA© SF. The data was statistically analysed through SPSS version 22 (SPSS Inc, Chicago, IL, USA). RESULTS: In this study 355 patients were enrolled and PG-SGA© SF results showed that 69.3% (n = 246) of the population presented at least one risk factor for malnourishment (Σ (box A) ≥1). Additionally, PG-SGA® revealed that 50% of patients (n = 177) have a risk of developing malnourishment or are already malnourished (B and C classification). The concordance of results showed to be high (coefficient k = 0.62; p < 0.001), meaning that PG-SGA SF© has a good sensibility (95%) and specificity (67%) for the identification of nutritional risk and assessment of nutritional status when compared with the complete version of PG-SGA©. CONCLUSIONS: According to our results, PG-SGA© SF is a useful and sufficient tool, representing an easier and faster way to identify at-risk or malnourished patients.

Effectiveness of Two Dietary Approaches on the Quality of Life and Gastrointestinal Symptoms of Individuals with Irritable Bowel Syndrome.

To evaluate the effectiveness of a low FODMAP (fermentable oligosaccharides, monosaccharaides, disaccharides and polyols) diet in the relief of symptoms and an improvement of the quality of life in individuals with irritable bowel syndrome in comparison to a standard diet according to the British Dietetic Association's guidelines. A non-randomized clinical trial of adult patients with IBS was compared two diet interventions. An assessment of symptoms, quality of life, and nutritional status was performed before and after the four-week mark of intervention. Individuals from the Low FODMAP Diet (LFD) group were evaluated on a third moment, after the controlled reintroduction of FODMAPs. A total of 70 individuals were divided in two groups: Low FODMAP Diet (LFD; n = 47) and Standard Diet (SD; n = 23). 57 individuals completed the four-week intervention (LFD; n = 39; SD; n = 18). At the completion of four weeks, the symptoms improved in both groups (LFD: p < 0.01; DC: p < 0.05) but LFD led to a higher relief (p < 0.05), primarily with respect to abdominal pain and diarrhoea. Quality of life improved significantly in both groups, with no significant differences between SD vs LFD (p > 0.05). In the LFD group, the relief of symptoms observed at the four-week mark remained constant after reintroduction of FODMAPs. Both interventions seem to be effective for the relief of symptoms and quality of life, however LFD had higher effectiveness in the former. The results with LFD suggest it can be a preferred approach in individuals with diarrhoeal profile.

Nutritional support in cirrhotic patients with sarcopenia.

Sarcopenia has been linked to oncologic and chronic diseases such as liver cirrhosis. In fact, sarcopenia is present in 25-70% of patients with liver cirrhosis. Furthermore, sarcopenia is an independent predictor of poor prognosis in many diseases. Currently cirrhotic patients are recommended to adopt a high protein diet (1.5 g/kg/day) with 30-40 kcal/kg/day and several meals throughout the day, being late evening snack intake with at least 50 g of carbohydrates of special importance. Despite the growing interest in the impact of sarcopenia in cirrhotic patients, there are still gaps in knowledge in the appropriate diagnostic criteria for this syndrome, the role of gut microbiota, as well as the most appropriate nutritional therapy.

Diet, Microbiota, and Gut Permeability-The Unknown Triad in Rheumatoid Arthritis.

Growing experimental and clinical evidence suggests that a chronic inflammatory response induced by gut dysbiosis can critically contribute to the development of rheumatic diseases, including rheumatoid arthritis (RA). Of interest, an adherence to a Mediterranean diet has been linked to a reduction in mortality and morbidity in patients with inflammatory diseases. Diet and intestinal microbiota are modifying factors that may influence intestinal barrier strength, functional integrity, and permeability regulation. Intestinal microbiota may play a crucial role in RA pathogenesis, but up to now no solid data has clarified a mechanistic relationship between gut microbiota and the development of RA. Nonetheless, microbiota composition in subjects with RA differs from that of controls and this altered microbiome can be partially restored after prescribing disease modifying antirheumatic drugs. High levels of Prevotella copri and similar species are correlated with low levels of microbiota previously associated with immune regulating properties. In addition, some nutrients can alter intestinal permeability and thereby influence the immune response without a known impact on the microbiota. However, critical questions remain to be elucidated, such as the way microbiome fluctuates in relation to diet, and how disease activity may be influenced by changes in diet, microbiota or diet-intestinal microbiota equilibrium.

A low fermentable oligo-di-mono-saccharides and polyols (FODMAP) diet is a balanced therapy for fibromyalgia with nutritional and symptomatic benefits

INTRODUCTION: Fibromyalgia is a chronic rheumatic disease producing widespread pain, associated to a major comorbidity -irritable bowel syndrome. Low FODMAPS diet (low fermentable oligo-di-mono-saccharides and polyols diet) has been effective in controlling irritable bowel syndrome symptoms. Overweight is an aggravating factor for fibromyalgia. We studied effects of low fermentable oligo-di-mono-saccharides and polyols diets on fibromyalgia symptoms and weight status. METHODS: A longitudinal study was performed on 38 fibromyalgia patients using a four-week, repeated assessment as follow: M1 = first assessments/presentation of individual low fermentable oligo-di-mono-saccharides and polyols diet; M2 = second assessments/reintroduction of FODMAPs; M3 = final assessments/nutritional counselling. The assessment instruments applied were: Fibromyalgia Survey Questionnaire (FSQ); Severity Score System (IBS-SSS); visual analogic scale (VAS). Body mass-index/composition and waist circumference (WC) were also measured. Daily macro-micronutrients and FODMAP intake were quantified at each moment of the study. RESULTS: The studied cohort was 37% overweight, 34% obese (average body mass-index 27.4 ± 4.6; excess fat mass 39.4 ± 7%). Weight, body mass-index and waist circumference decreased significantly (p < 0.01) with low fermentable oligo-di-mono-saccharides and polyols diet, but no significant effect on body composition was observed. All fibromyalgiasymptoms, including somatic pain, declined significantly post-LFD (p < 0.01); as well for severity of fibromyalgia [Fibromyalgia survey questionnaire: M1 = 21.8; M2 = 16.9; M3 = 17.0 (p < 0.01)]. The intake of essential nutrients (fiber, calcium, magnesium and vitamin D) showed no significant difference. The significant reduction in FODMAP intake (M1 = 24.4 g; M2 = 2.6g; p < 0.01) reflected the "Diet adherence" (85%). "Satisfaction with improvement of symptoms" (76%), showed correlating with "diet adherence" (r = 0.65; p < 0.01). CONCLUSIONS: Results are highly encouraging, showing low fermentable oligo-di-mono-saccharides and polyols diets as a nutritionally balanced approach, contributing to weight loss and reducing the severity of FM fibromyalgiasymptoms.

A low fermentable oligo-di-mono-saccharides and polyols (FODMAP) diet is a balanced therapy for fibromyalgia with nutritional and symptomatic benefits / Una dieta baja en oligo-, di- y monosacáridos (FODMAPs) es un tratamiento adecuado para pacientes con fibromialgia, con beneficios clínicos y nutricionales

Introduction: Fibromyalgia is a chronic rheumatic disease producing widespread pain, associated to a major comorbidity -irritable bowel syndrome. Low FODMAPS diet (low fermentable oligo-di-mono-saccharides and polyols diet) has been effective in controlling irritable bowel syndrome symptoms. Overweight is an aggravating factor for fibromyalgia. We studied effects of low fermentable oligo-di-mono-saccharides and polyols diets on fibromyalgia symptoms and weight status. Methods: A longitudinal study was performed on 38 fibromyalgia patients using a four-week, repeated assessment as follow: M1 = first assessments/presentation of individual low fermentable oligo-di-mono-saccharides and polyols diet; M2 = second assessments/reintroduction of FODMAPs; M3 = final assessments/nutritional counselling. The assessment instruments applied were: Fibromyalgia Survey Questionnaire (FSQ); Severity Score System (IBS-SSS); visual analogic scale (VAS). Body mass-index/composition and waist circumference (WC) were also measured. Daily macro-micronutrients and FODMAP intake were quantified at each moment of the study. Results: The studied cohort was 37% overweight, 34% obese (average body mass-index 27.4 ± 4.6; excess fat mass 39.4 ± 7%). Weight, body mass-index and waist circumference decreased significantly (p < 0.01) with low fermentable oligo-di-mono-saccharides and polyols diet, but no significant effect on body composition was observed. All fibromyalgia symptoms, including somatic pain, declined significantly post-LFD (p < 0.01); as well for severity of fibromyalgia [Fibromyalgia survey questionnaire: M1 = 21.8; M2 = 16.9; M3 = 17.0 (p < 0.01)]. The intake of essential nutrients (fiber, calcium, magnesium and vitamin D) showed no significant difference. The significant reduction in FODMAP intake (M1 = 24.4 g; M2 = 2.6g; p < 0.01) reflected the «Diet adherence» (85%). «Satisfaction with improvement of symptoms» (76%), showed correlating with «diet adherence» (r = 0.65; p < 0.01). Conclusions: Results are highly encouraging, showing low fermentable oligo-di-mono-saccharides and polyols diets as a nutritionally balanced approach, contributing to weight loss and reducing the severity of FM fibromyalgia symptoms (AU)

Introducción: la fibromialgia es una enfermedad reumática crónica, que tiene unas importantes comorbilidades-síndrome del intestino irritable (SII). La dieta baja en FODMAPs (low fermentable oligo-di-mono-saccharides and polyols diet) ha sido eficaz en el tratamiento del síndrome del intestino irritable. El sobrepeso es un factor agravante. Se estudiaron los efectos nutricionales del FODMAPs en la fibromialgia. Métodos: estudio longitudinal en 38 pacientes con fibromialgia en el que se utilizó una evaluación repetida, durante cuatro semanas, de lo siguiente: Moment 1 (M1) = primeras evaluaciones/presentación de FODMAPs; M2 = segundas evaluaciones/reintroducción de FODMAPs; M3 = evaluaciones finales/asesoramiento nutricional. Instrumentos de evaluación: Fibromialgia Survey Questionnaire; síndrome del intestino irritable (IBS-SSS), escala visual analógica (EVA) y parámetros antropométricos. Cuantificación en todo momento de las ingestas diarias de macro/micro nutrientes y FODMAPs. Resultados: el estudio de cohorte mostró 37% de sobrepeso y 34% obesidad; índice de masa corporal = 27,4 ± 4,6; masa grasa = 39,4 ± 7%. El peso y la circunferencia de la cintura disminuyeron significativamente con FODMAPs, pero no cambió la composición corporal. Los síntomas y la severidad de la fibromialgia (FSQ: M1 = 21,8; M2 = 16,9; M3 = 17,0) se redujeron significativamente después de FODMPAs (p < 0,01). No fueron observadas diferencias significativas en el consumo de nutrientes esenciales, especialmente la fi bra, calcio, magnesio y vitamina D. El «seguimiento de la dieta» fue del 85% con reducción significativa de la ingesta de FODMAPs (p < 0,01: M1 = 24,4 g; M2 = 2,6 g). «La satisfacción con la mejora de los síntomas» (76%) se correlacionó con el «seguimiento de la dieta» (r = 0,65; p < 0,01). Conclusiones: los resultados son muy alentadores, mostrando FODMAPs como un enfoque equilibrado nutricionalmente, que contribuyó a la pérdida de peso y redujo significativamente la severidad de la FM (AU)

Risk factors for metabolic bone disease in Crohn's disease patients.

BACKGROUND: The aim was to evaluate the presence of metabolic bone disease (MBD) in patients with Crohn's disease (CD) and to identify potential etiologic factors. METHODS: The case-control study included 99 patients with CD and 56 controls with a similar age and gender distribution. Both groups had dual-energy x-ray absorptionmetry and a nutritional evaluation. Single nucleotide polymorphisms at the IL1, TNF-α, LTα, and IL-6 genes were analyzed in patients only. Statistical analysis was performed using SPSS software. RESULTS: The prevalence of MBD was significantly higher in patients (P = 0.006). CD patients with osteoporosis were older (P < 0.005), small bowel involvement and surgical resections were more frequent (P < 0.005), they more often exhibited a penetrating or stricturing phenotype (P < 0.05), duration of disease over 15 years (P < 0.005), and body mass index (BMI) under 18.5 kg/m(2) (P < 0.01) were more often found. No association was found with steroid use. Patients with a Z-score < -2.0 more frequently had chronic active disease (P < 0.05). With regard to diet, low vitamin K intake was more frequent (P = 0.03) and intake of total, monounsaturated, and polyunsaturated fat was higher in patients with Z-score < -2.0 (P < 0.05). With respect to genetics, carriage of the polymorphic allele for LTα252 A/G was associated with a higher risk of osteoporosis (P = 0.02). Regression analysis showed that age over 40 years, chronic active disease, and previous colonic resections were independently associated with the risk of developing MBD. CONCLUSIONS: The prevalence of MBD was significantly higher in CD patients. Besides the usual risk factors, we observed that factors related to chronic active and long-lasting disease increased the risk of MBD.

Fat intake interacts with polymorphisms of Caspase9, FasLigand and PPARgamma apoptotic genes in modulating Crohn's disease activity.

BACKGROUND & AIMS: Crohn's disease (CD) is a multifactorial disease where resistance to apoptosis is one major defect. Also, dietary fat intake has been shown to modulate disease activity. We aimed to explore the interaction between four single nucleotide polymorphisms (SNPs) in apoptotic genes and dietary fat intake in modulating disease activity in CD patients. METHODS: Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) techniques were used to analyze Caspase9+93C/T, FasLigand-843C/T, Peroxisome Proliferator-Activated Receptor gamma+161C/T and Peroxisome Proliferator-Activated Receptor gamma Pro12Ala SNPs in 99 patients with CD and 116 healthy controls. Interactions between SNPs and fat intake in modulating disease activity were analyzed using regression analysis. RESULTS: None of the polymorphisms analyzed influenced disease susceptibility and/or activity, but a high intake of total, saturated and monounsaturated fats and a higher ratio of n-6/n-3 polyunsaturated fatty acids(PUFA), was associated with a more active phenotype (p < 0.05). We observed that the detrimental effect of a high intake of total and trans fat was more marked in wild type carriers of the Caspase9+93C/T polymorphism [O.R(95%CI) 4.64(1.27-16.89) and O.R(95%CI) 4.84(1.34-17.50)]. In the Peroxisome Proliferator-Activated Receptor gamma Pro12Ala SNP, we also observed that a high intake of saturated and monounsaturated fat was associated to a more active disease in wild type carriers [OR(95%CI) 4.21(1.33-13.26) and 4.37(1.52-12.51)]. Finally, a high intake of n-6 PUFA was associated with a more active disease in wild type carriers for the FasLigand-843C/T polymorphism [O.R(95%CI) 5.15(1.07-24.74)]. CONCLUSIONS: To our knowledge, this is the first study to disclose a synergism between fat intake and SNPs in apoptotic genes in modulating disease activity in CD patients.

Fatty acids, IL6, and TNFalpha polymorphisms: an example of nutrigenetics in Crohn's disease.

OBJECTIVES: The aim of this work was to study the interaction between genetic polymorphisms (single-nucleotide polymorphisms, SNPs) of pro- and anti-inflammatory cytokines and fat intake on the risk of developing Crohn's disease (CD) or modifying disease activity. METHODS: Seven SNPs in interleukin 1 (IL1), tumor necrosis factor alpha (TNFalpha), lymphotoxin alpha (LTalpha), and IL6 genes were analyzed in 116 controls and 99 patients with CD. The type of fat intake was evaluated, and the interaction between SNPs and dietary fat in modulating disease activity was analyzed. RESULTS: Individuals who were homozygous for the IL6-174G/C polymorphism had a six-fold higher risk for CD (odds ratio (OR)=6.1; 95% confidence interval (95% CI)=1.9-19.4), whereas the TT genotype on the TNFalpha-857C/T polymorphism was associated with more active disease (OR=10.4; 95% CI=1.1-94.1). A high intake of total, saturated, and monounsaturated fats, as well as a higher ratio of n-6/n-3 polyunsaturated fatty acid (PUFA), was associated with a more active phenotype (P<0.05). Furthermore, there was an interaction between dietary fat intake and SNPs, with a high intake of saturated and monounsaturated fats being associated with active disease, mainly in patients carrying the variant alleles of the 857 TNFalpha polymorphism (OR=6.0, 95% CI=1.4-26.2; OR=5.17; 95% CI=1.4-19.2, respectively) and the 174 IL6 polymorphism (OR=2.95; 95% CI=1.0-9.1; OR=3.21; 95% CI=1.0-10.4, respectively). Finally, low intake of n-3 PUFA and high n-6/n-3 PUFA ratio in patients with the TNFalpha 857 polymorphism were associated with higher disease activity (OR=3.6; 95% CI=1.0-13.0; OR=5.92; 95% CI=1.3-26.5, respectively). CONCLUSIONS: These results show that different types of fat may interact with cytokine genotype, modulating disease activity.

Risk of colorectal cancer associated with the C677T polymorphism in 5,10-methylenetetrahydrofolate reductase in Portuguese patients depends on the intake of methyl-donor nutrients.

BACKGROUND: Polymorphisms located in genes involved in the metabolism of folate and some methyl-related nutrients are implicated in colorectal cancer (CRC). OBJECTIVE: We evaluated the association of 3 genetic polymorphisms [C677T MTHFR (methylene tetrahydrofolate reductase), A2756G MTR (methionine synthase), and C1420T SHMT (serine hydroxymethyltransferase)] with the intake of methyl-donor nutrients in CRC risk. DESIGN: Patients with CRC (n = 196) and healthy controls (n = 200) matched for age and sex were evaluated for intake of methyl-donor nutrients and the 3 polymorphisms. RESULTS: Except for folate intake, which was significantly lower in patients (P = 0.02), no differences were observed in the dietary intake of other methyl-donor nutrients between groups. High intake of folate (>406.7 microg/d) was associated with a significantly lower risk of CRC (odds ratio: 0.67; 95% CI: 0.45, 0.99). The A2756G MTR polymorphism was not associated with the risk of developing CRC. In contrast, homozygosity for the C677T MTHFR variant (TT) presented a 3.0-fold increased risk of CRC (95% CI: 1.3, 6.7). Similarly, homozygosity for the C1420T SHMT polymorphism also had a 2.6-fold increased risk (95% CI: 1.1, 5.9) of developing CRC. When interactions between variables were studied, low intake of all methyl-donor nutrients was associated with an increased risk of CRC in homozygous participants for the C677T MTHFR polymorphism, but a statistically significant interaction was only observed for folate (odds ratio: 14.0; 95% CI: 1.8, 108.5). No significant associations were seen for MTR or SHMT polymorphisms. CONCLUSION: These results show an association between the C677T MTHFR variant and different folate intakes on risk of CRC.