Research - B Vitamins
Vitamin B-6 catabolism and long-term mortality risk in patients with coronary artery disease
- Arve Ulvik3,*,
- Eva R Pedersen4,
- Gard FT Svingen4,
- Adrian McCann3,
- Øivind Midttun3,
- Ottar Nygård4,5, and
- Per M Ueland4,6
Background: Low vitamin B-6 status has been related to increased risk of coronary artery disease (CAD), which is a condition that is associated with inflammation. The most common status marker, plasma pyridoxal 5′-phosphate (PLP), decreases during inflammation; therefore, causal relations are uncertain.
Objective: We evaluated the vitamin B-6 biomarkers PLP, pyridoxal, and pyridoxic acid (PA) and the pyridoxic acid:(pyridoxal + PLP) ratio (PAr), a proposed marker of vitamin B-6 catabolism during activated cellular immunity, as predictors of mortality.
Design: Associations with risks of long-term all-cause mortality and cardiovascular mortality were evaluated with the use of Cox regression in patients who were undergoing elective coronary angiography for suspected stable angina pectoris (SAP) (n = 4131) and an independent cohort of patients who were hospitalized for acute myocardial infarction (AMI) (n = 3665).
Results: Plasma PLP (AMI patients only) and PA predicted all-cause mortality in models that were adjusted for established risk predictors, but associations were attenuated or nonsignificant after additional adjustment for inflammatory markers. PAr was correlated with biomarkers of inflammation (Pearson’s r ≥ 0.37) and predicted all-cause mortality and cardiovascular mortality after adjustment for established risk predictors. In SAP patients, PAr had greater predictive strength than did current smoking, diabetes, hypertension, apolipoproteins, or C-reactive protein. PAr provided multiadjusted HRs per SD of 1.45 (95% CI: 1.30, 1.63) and 1.31 (95% CI: 1.21, 1.41) in SAP and AMI patients, respectively. In both cohorts, PAr was a particularly strong predictor of all-cause mortality for patients with no previous CAD history (P-interaction ≤ 0.04).
Conclusion: PAr may capture unique aspects of inflammatory activation and thus provide new insights into disease mechanisms that may aid in identifying patients at increased risk of future fatal events.
Source : American Journal of Clinical Nutrition
Link to Full Article
A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention
Andrew C. Chen, M.B., B.S., Andrew J. Martin, Ph.D., Bonita Choy, M.Med., Pablo Fernández-Peñas, Ph.D., Robyn A. Dalziell, Ph.D., Catriona A. McKenzie, M.B., B.S., Richard A. Scolyer, M.D., Haryana M. Dhillon, Ph.D., Janette L. Vardy, M.D., Anne Kricker, Ph.D., Gayathri St. George, M.Sc.Med., Niranthari Chinniah, M.B., B.S., Gary M. Halliday, D.Sc., and Diona L. Damian, Ph.D.
Nonmelanoma skin cancers, such as basal-cell carcinoma and squamous-cell carcinoma, are common cancers that are caused principally by ultraviolet (UV) radiation. Nicotinamide (vitamin B3) has been shown to have protective effects against damage caused by UV radiation and to reduce the rate of new premalignant actinic keratoses.
In this phase 3, double-blind, randomized, controlled trial, we randomly assigned, in a 1:1 ratio, 386 participants who had had at least two nonmelanoma skin cancers in the previous 5 years to receive 500 mg of nicotinamide twice daily or placebo for 12 months. Participants were evaluated by dermatologists at 3-month intervals for 18 months. The primary end point was the number of new nonmelanoma skin cancers (i.e., basal-cell carcinomas plus squamous-cell carcinomas) during the 12-month intervention period. Secondary end points included the number of new squamous-cell carcinomas and basal-cell carcinomas and the number of actinic keratoses during the 12-month intervention period, the number of nonmelanoma skin cancers in the 6-month postintervention period, and the safety of nicotinamide.
At 12 months, the rate of new nonmelanoma skin cancers was lower by 23% (95% confidence interval [CI], 4 to 38) in the nicotinamide group than in the placebo group (P=0.02). Similar differences were found between the nicotinamide group and the placebo group with respect to new basal-cell carcinomas (20% [95% CI, −6 to 39] lower rate with nicotinamide, P=0.12) and new squamous-cell carcinomas (30% [95% CI, 0 to 51] lower rate, P=0.05). The number of actinic keratoses was 11% lower in the nicotinamide group than in the placebo group at 3 months (P=0.01), 14% lower at 6 months (P<0.001), 20% lower at 9 months (P<0.001), and 13% lower at 12 months (P=0.001). No noteworthy between-group differences were found with respect to the number or types of adverse events during the 12-month intervention period, and there was no evidence of benefit after nicotinamide was discontinued.
Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients.
Source : New England Journal of Medicine
Link to Abstract
Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3fatty acids and B vitamin status in a randomized controlled trial1,2,3,4
- Fredrik Jernerén⇑,
- Amany K Elshorbagy,
- Abderrahim Oulhaj,
- Stephen M Smith,
- Helga Refsum, and
- A David Smith
Background: Increased brain atrophy rates are common in older people with cognitive impairment, particularly in those who eventually convert to Alzheimer disease. Plasma concentrations of omega-3 (ω-3) fatty acids and homocysteine are associated with the development of brain atrophy and dementia.
Objective: We investigated whether plasma ω-3 fatty acid concentrations (eicosapentaenoic acid and docosahexaenoic acid) modify the treatment effect of homocysteine-lowering B vitamins on brain atrophy rates in a placebo-controlled trial (VITACOG).
Design: This retrospective analysis included 168 elderly people (≥70 y) with mild cognitive impairment, randomly assigned either to placebo (n = 83) or to daily high-dose B vitamin supplementation (folic acid, 0.8 mg; vitamin B-6, 20 mg; vitamin B-12, 0.5 mg) (n = 85). The subjects underwent cranial magnetic resonance imaging scans at baseline and 2 y later. The effect of the intervention was analyzed according to tertiles of baseline ω-3 fatty acid concentrations.
Results: There was a significant interaction (P = 0.024) between B vitamin treatment and plasma combined ω-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) on brain atrophy rates. In subjects with high baseline ω-3fatty acids (>590 μmol/L), B vitamin treatment slowed the mean atrophy rate by 40.0% compared with placebo (P = 0.023). B vitamin treatment had no significant effect on the rate of atrophy among subjects with low baseline ω-3 fatty acids (<390 μmol/L). High baseline ω-3 fatty acids were associated with a slower rate ofbrain atrophy in the B vitamin group but not in the placebo group.
Conclusions: The beneficial effect of B vitamin treatment on brain atrophy was observed only in subjects with high plasma ω-3 fatty acids. It is also suggested that the beneficial effect of ω-3 fatty acids on brain atrophy may be confined to subjects with good B vitamin status. The results highlight the importance of identifying subgroups likely to benefit in clinical trials.
Source : American Journal of Clinical Nutrition
Link to Abstract
Association between intake of B vitamins and cognitive function in elderly Koreans with cognitive impairment
Hyesook Kim1, Ggotpin Kim1, Won Jang1, Seong Yoon Kim2 and Namsoo Chang1
Background It is possible that blood B vitamins level and cognitive function may be affected by dietary intake of these vitamins, no study however has yet been conducted on relationships between B vitamins intake and cognitive function among elderly population in Korea. This study examined the relationship between B vitamins intake and cognitive function among elderly in South Korea.
Methods Participants consisted of 100 adults with mild cognitive impairment (MCI), 100 with Alzheimer’s disease (AD), and 121 normal subjects. Dietary intake data that included the use of dietary supplements were obtained using a 24-hour recall method by well-trained interviewers. Plasma folate and vitamin B12 concentrations were analyzed by radioimmunoassay, and homocysteine (Hcy) was assessed by a high performance liquid chromatography-fluorescence method.
Results Plasma levels of folate and vitamin B12 were positively correlated with B vitamins intake; and plasma Hcy was negatively correlated with total intake of vitamin B2, vitamin B6, vitamin B12 and folate. In the AD group, a multiple regression analysis after adjusting for covariates revealed positive relationships between vitamin B2 intake and test scores for the MMSE-KC, Boston Naming, Word Fluency, Word List Memory and Constructional Recall Tests; and between vitamin B6 intake and the MMSE-KC, Boston Naming, Word Fluency, Word List Memory, Word List Recognition, Constructional Recall and Constructional Praxis Tests. Positive associations were observed between vitamin B12 intake and the MMSE-KC, Boston Naming, Constructional Recall and Constructional Praxis Tests, and between folate intake and the Constructional Recall Test. In the MCI group, vitamin B2 intake was positively associated with the MMSE-KC and Boston Naming Test, vitamin B6 intake was positively associated with the Boston Naming Test, and folate intake was positively associated with the MMSE-KC and Word List Memory test. No associations were observed in the normal group.
Conclusion These results suggested that total B vitamins intake is associated with cognitive function in cognitively impaired AD and MCI elderly, and the association is stronger in AD patients.
Source : Nutrition Journal
Link to Full Article
Folic acid deficiency induces premature hearing loss through mechanisms involving cochlear oxidative stress and impairment of homocysteine metabolism
- Raquel Martínez-Vega*,†,
- Francisco Garrido*,
- Teresa Partearroyo‡,
- Rafael Cediel*,†§,
- Steven H. Zeisel‖,
- Concepción Martínez-Álvarez¶,
- Gregorio Varela-Moreiras‡,
- Isabel Varela-Nieto*,†#,1,2 and
- María A. Pajares*,#
Nutritional imbalance is emerging as a causative factor of hearing loss. Epidemiologic studies have linked hearing loss to elevated plasma total homocysteine (tHcy) and folate deficiency, and have shown that folate supplementation lowers tHcy levels potentially ameliorating age-related hearing loss. The purpose of this study was to address the impact of folate deficiency on hearing loss and to examine the underlying mechanisms. For this purpose, 2-mo-old C57BL/6J mice (Animalia Chordata Mus musculus) were randomly divided into 2 groups (n = 65 each) that were fed folate-deficient (FD) or standard diets for 8 wk. HPLC analysis demonstrated a 7-fold decline in serum folate and a 3-fold increase in tHcy levels. FD mice exhibited severe hearing loss measured by auditory brainstem recordings and TUNEL-positive-apoptotic cochlear cells. RT-quantitative PCR and Western blotting showed reduced levels of enzymes catalyzing homocysteine (Hcy) production and recycling, together with a 30% increase in protein homocysteinylation. Redox stress was demonstrated by decreased expression of catalase, glutathione peroxidase 4, and glutathione synthetase genes, increased levels of manganese superoxide dismutase, and NADPH oxidase-complex adaptor cytochrome b-245, α-polypeptide (p22phox) proteins, and elevated concentrations of glutathione species. Altogether, our findings demonstrate, for the first time, that the relationship between hyperhomocysteinemia induced by folate deficiency and premature hearing loss involves impairment of cochlear Hcy metabolism and associated oxidative stress.
Source : FASB Journal
Link to Abstract
Dietary Folate Intake and Breast Cancer Risk: European Prospective Investigation Into Cancer and Nutrition
Background: There is limited evidence on the association between dietary folate intake and the risk of breast cancer (BC) by hormone receptor expression in the tumors. We investigated the relationship between dietary folate and BC risk using data from the European Prospective Investigation into Cancer and Nutrition (EPIC).
Methods: A total of 367993 women age 35 to 70 years were recruited in 10 European countries. During a median follow-up of 11.5 years, 11575 women with BC were identified. Dietary folate intake was estimated from country-specific dietary questionnaires. Cox proportional hazards regression models were used to quantify the association between dietary variables and BC risk. BC tumors were classified by receptor status. Subgroup analyses were performed by menopausal status and alcohol intake. Intake of other B vitamins was considered. All statistical tests were two-sided.
Results: A borderline inverse association was observed between dietary folate and BC risk (hazard ratio comparing top vs bottom quintile [HRQ5-Q1] = 0.92, 95% CI = 0.83 to 1.01, P trend = .037). In premenopausal women, we observed a statistically significant trend towards lower risk in estrogen receptor-negative BC (HRQ5-Q1 = 0.66, 95% CI = 0.45 to 0.96, Ptrend = .042) and progesterone receptor-negative BC (HRQ5-Q1 = 0.70, 95% CI = 0.51 to 0.97, P trend = .021). No associations were found in postmenopausal women. A 14% reduction in BC risk was observed when comparing the highest with the lowest dietary folate tertiles in women having a high (>12 alcoholic drinks/week) alcohol intake (HRT3-T1 = 0.86, 95% CI = 0.75 to 0.98, P interaction = .035).
Conclusions: Higher dietary folate intake may be associated with a lower risk of sex hormone receptor–negative BC in premenopausal women.
Source : Journal of National Cancer Institute
Link to Abstract
Homocysteine, vitamin B12 and folate levels in premature coronary artery disease
Saeed Sadeghian1*, Faramarz Fallahi2, Mojtaba Salarifar3, Gholamreza Davoodi1, Mehran Mahmoodian4, Nader Fallah5, Soodabeh Darvish4, Abbasali Karimi6 and Tehran Heart Center
1 Assistant Professor of Cardiology, Research Department, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
2 Assistant Professor of Cardiology, Shahed University, Tehran, Iran
3 Assistant Professor of Interventional Cardiology, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
4 Researcher, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
5 Regular member of board, Department of Biostatistics, Shahed University, Tehran, Iran
6 Associated Professor of cardiac surgery, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
Background Hyperhomocysteinemia is known as an independent risk factor of atherosclerosis, but the probable role of hyperhomocysteinemia in premature Coronary Artery Disease (CAD) is not well studied. The aim of this study was to assess the role of hyperhomocysteinemia, folate and Vitamin B12 deficiency in the development of premature CAD.
Methods We performed an analytical case-control study on 294 individuals under 45 years (225 males and 69 females) who were admitted for selective coronary angiography to two centers in Tehran.
Results After considering the exclusion criteria, a total number of 225 individuals were enrolled of which 43.1% had CAD. The mean age of participants was 39.9 +/- 4.3 years (40.1 +/- 4.2 years in males and 39.4 +/- 4.8 years in females). Compared to the control group, the level of homocysteine measured in the plasma of the male participants was significantly high (14.9 +/- 1.2 versus 20.3 +/- 1.9 micromol/lit, P = 0.01). However there was no significant difference in homocysteine level of females with and without CAD (11.8 +/- 1.3 versus 11.5 ± 1.1 micromol/lit, P = 0.87). Mean plasma level of folic acid and vitamin B12 in the study group were 6.3 +/- 0.2 and 282.5 +/- 9.1 respectively. Based on these findings, 10.7% of the study group had folate deficiency while 26.6% had Vitamin B12 deficiency. Logistic regression analysis for evaluating independent CAD risk factors showed hyperhomocysteinemia as an independent risk factor for premature CAD in males (OR = 2.54 0.95% CI 1.23 to 5.22, P = 0.01). Study for the underlying causes of hyperhomocysteinemia showed that male gender and Vitamin B12 deficiency had significant influence on incidence of hyperhomocysteinemia.
Conclusion We may conclude that hyperhomocysteinemia is an independent risk factor for CAD in young patients (bellow 45 years old) – especially in men -and vitamin B12 deficiency is a preventable cause of hyperhomocysteinemia.
Source : BMC Cardiovascular Disorders
Link to Full Article
A Prospective Study of Folate, Vitamin B6, and Vitamin B12 Intake in Relation to Exfoliation Glaucoma or Suspected Exfoliation Glaucoma.
Kang JH1, Loomis SJ2, Wiggs JL2, Willett WC3, Pasquale LR4.
IMPORTANCE Effective strategies for primary prevention are lacking for exfoliation glaucoma (EG), which is the most common type of secondary glaucoma.
OBJECTIVE To examine the association between B vitamin intake and EG or suspected EG (EG/SEG) risk. DESIGN, SETTING, AND
PARTICIPANTS National prospective cohort study using more than 20 years of follow-up data from the Nurses' Health Study (all female registered nurses) and the Health Professionals Follow-up Study (all male health professionals) from June 1, 1980, to May 31, 2010 (Nurses' Health Study) and January 1, 1986, to December 31, 2010 (Health Professionals Follow-up Study). We included a subset of 78 980 Nurses' Health Study women and 41 221 Health Professionals Follow-up Study men who were 40 years or older, free of glaucoma, had completed diet questionnaires, and reported eye examinations (follow-up rate, >85%). EXPOSURES Cumulatively updated intake of B vitamins (folate, vitamin B6, and vitamin B12) as ascertained by repeated administration of validated questionnaires.
MAIN OUTCOMES AND MEASURES Incident cases of EG/SEG, totaling 399 (329 women and 70 men), were first identified with the questionnaires and were subsequently confirmed with medical records. Multivariable relative risks for EG/SEG were calculated in each cohort and then pooled with meta-analysis. RESULTS Vitamin B6 and vitamin B12 intake was not associated with EG/SEG risk in pooled analyses (P = .52 and P = .99 for linear trend, respectively). However, a suggestive trend of a reduced risk was observed with higher intake of folate: compared with the lowest quintile of cumulatively averaged updated total folate intake, the multivariable relative risk for EG/SEG for the highest quintile (≥654 μg/d) was 0.75 (95% CI, 0.54-1.04; P = .02 for linear trend). These results were not materially altered after adjustment for vitamin B6 and vitamin B12 intake. An association was observed for supplemental folate intake but not for dietary folate only (P = .03 and P = .64 for linear trend, respectively). Greater frequency of multivitamin use showed a modest suggestive inverse association (current multivitamin use of ≥6 times per week vs nonuse multivariable relative risk, 0.84; 95% CI, 0.64-1.11; P = .06 for linear trend).
CONCLUSIONS AND RELEVANCE Higher total folate intake was associated with a suggestive lower risk for EG/SEG, supporting a possible causal role of homocysteine in EG/SEG.
Source : JAMA Opthalmol
Link to Abstract
Co-occurrence of Anemia, Marginal Vitamin B6, and Folate Status and Depressive Symptoms in Older Adults
Wen-Harn Pan, PhD1,2,3,4⇓, Yi-Ping Chang, EdD5, Wen-Ting Yeh, MS2, Yu-Shu Guei, BS6, Bi-Fong Lin, PhD3, Ien-Lan Wei, PhD7, Feili Lo Yang, PhD8, Yung-Po Liaw, PhD6,9, Kuan-Ju Chen, PhD10, Wei J. Chen, MD, ScD4
- 1Nutrition Medicine Research Program, Division of Preventive Medicine and Health Services Research, Institute of Population Health Sciences, National Health Research Institutes, Maoli, Taiwan
- 2Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
- 3Institute of Microbiology and Biochemistry, National Taiwan University, Taipei, Taiwan
- 4Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan
- 5Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
- 6Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, Taiwan
- 7School of Nursing, National Yang-Ming University, Taipei, Taiwan
- 8Department of Nutrition and Food Sciences, Fu-Jen University, Hsin-Chung, Taipei, Taiwan
- 9Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
- 10Department of Hospitality Management, Chung Hwa University of Medical Technology, Tainan County, Taiwan
- Wen-Harn Pan, Nutrition Medicine Research Program, Division of Preventive Medicine and Health Services Research, Institute of Population Health Sciences, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan OR Institute of Biomedical Sciences, Academia Sinica, no. 128, Section 2, Academia Road, Taipei 14529, Taiwan Email: email@example.com OR firstname.lastname@example.org
Although nutrient deficiencies are thought to play roles in the development of depression, observational studies have yielded inconsistent results. This study aimed to investigate whether multiple marginal nutrient deficiencies are associated with symptoms of depression in community-dwelling older Taiwanese. Data from 1371 elderly adults recruited from the Elderly Nutrition and Health Survey in Taiwan was used in this study. Depressive symptom scores on depressed mood and emotions affecting daily life were derived from the Medical Outcomes Study Short Form-36 (SF-36). Hemoglobin, serum ferritin, plasma vitamins B6, B12, and folate concentration, and erythrocyte transketolase and glutathione reductase activation coefficients were measured. After adjusting for age, gender, cognitive function, physical activity, disease history, and medication in the multivariate analysis, anemia, and marginal B6 deficiency were significantly associated with the presence of depression symptoms, respectively. In addition, co-occurrence of vitamin B6 with low folate level and co-occurrence of anemia either with low vitamin B6 or with folate level were all associated with the depressive mood and with depressive emotions defined by SF-36 (odds ratios [OR] in the range of 2.32−7.13, all P values ≤.05). The magnitude of the ORs is larger when the number of deficiencies increased. Elderly people with coexisting marginal deficiencies of nutrients involved in the S-adenosylmethionine and hemoglobin production were more likely to experience depressed mood and emotion that affect daily activity. Examining status of these nutrients is worthy of consideration for older adults with depressed symptoms.
Source : J Geriatr Psychiatry Neurol
Link to Abstract
Natural Niacin Beats Prescription Zetia for Cholesterol
A study published in the New England Journal of Medicine concluded that niacin, also known as vitamin B3, is better for reducing cholesterol and preventing heart disease than Merck & Co., Inc.'s prescription medication Zetia.
Researchers found that over a 14 month period niacin was significantly more effective at reducing artery plaque than ezetimibe, the active ingredient in Zetia. In addition, niacin was found more effective than Zetia at decreasing the number of heart attacks.
Zetia is a medication used in conjunction with statins to try to further lower levels of the so-called bad LDL cholesterol in the blood. It claims to work by blocking the absorption of cholesterol in the digestive track. Annual sales of the drug in 2010 were $2 billion.
The study was halted early because the niacin group was doing better. In fact, the researchers concluded that the more LDL cholesterol was reduced in the Zetia group, the greater was the progression of their atherosclerosis. In addition, there were significantly more major cardiovascular events among patients using Zetia than among those in the niacin group.
The lead author of the study questioned whether Zetia was effective at all and concluded that "prudent clinical practice currently favors the avoidance of ezetimibe" until further clinical studies are conducted.
What is niacin? Niacin is a water soluble B vitamin also known as "nicotinic acid" used by the body to convert carbohydrates, fats and protein into energy. It also contributes to keeping the nervous system, digestive system, skin, hair and eyes healthy.
Niacin has been used for over 50 years as an effective method for raising the levels of good HDL cholesterol in the blood and is also known to help reduce bad LDL cholesterol and triglycerides.
What foods contain niacin? Niacin is widely available in the food supply. The principal food sources of niacin include:
• Dairy products
• Lean meats
• Nutritional yeast
• Wheat germ
• Whole grains
Most people get sufficient niacin in their daily diets. Minimum requirements are 14-16 milligrams per day to prevent pellagra, a disease characterized by diarrhea, dementia and dermatitis. If left untreated it can lead to death.
Pellagra was widespread when people ate a diet heavy in corn rather than other whole grains since corn is very low in niacin. Native Americans traditionally cooked corn with lime because lime improves niacin absorption in the body, thus preventing the disease.
The optimum daily amount of niacin has not been set but a typical multi-vitamin will contain 20 milligrams, and many B complex vitamin supplements will contain as much as 200 milligrams.
Niacin for cholesterol control The idea that there are "bad" and "good" blood lipids that contribute to heart disease is known as the "lipid hypothesis," or "cholesterol myth." The hypothesis is subject to much criticism and has been challenged often.
Nevertheless, most doctors continue to use cholesterol numbers to determine treatment. For treating high cholesterol, prescription doses of niacin are typically used only under a doctor's supervision.
Source : Green Med Info
Link to Source