Induced apoptosis of autoreactive T-lymphocyte precursors in the thymus is crucial for the prevention of autoimmune disorders. IGF-I and prolactin, which are lymphocyte growth factors, may have the potential to suppress apoptosis in thymocytes and thus encourage autoimmunity; conversely, dietary fish oil rich in omega-3 fats appears to upregulate apoptosis in lymphocytes. Since whole-food vegan diets may downregulate systemic IGF-I activity, it is proposed that such a diet, in conjunction with fish oil supplementation and treatment with dopamine agonists capable of suppressing prolactin secretion, may have utility for treating and preventing autoimmune disorders. This prediction is consistent with the extreme rarity of autoimmune disorders among sub-Saharan black Africans as long as they followed their traditional quasi-vegan lifestyles, and with recent ecologic studies correlating risks for IDDM and for multiple sclerosis mortality with animal product and/or saturated fat consumption. Moreover, there is evidence that vegan or quasi-vegan diets are useful in the management of rheumatoid arthritis, multiple sclerosis, and possibly SLE. The dopamine agonist bromocryptine exerts anti-inflammatory effects in rodent models of autoimmunity, and there is preliminary evidence that this drug may be clinically useful in several human autoimmune diseases; better tolerated D2-specific agonists such as cabergoline may prove to be more practical for use in therapy. The moderate clinical utility of supplemental fish oil in rheumatoid arthritis and certain other autoimmune disorders is documented. It is not unlikely that extra-thymic anti-inflammatory effects contribute importantly to the clinical utility of vegan diets, bromocryptine, and fish oil in autoimmunity. The favorable impact of low latitude or high altitude on autoimmune risk may be mediated by superior vitamin D status, which is associated with decreased secretion of parathyroid hormone; there are theoretical grounds for suspecting that parathyroid hormone may inhibit apoptosis in thymocytes. Androgens appear to up-regulate thymocyte apoptosis, may be largely responsible for the relative protection from autoimmunity enjoyed by men, and merit further evaluation for the management of autoimmunity in women. It will probably prove more practical to prevent autoimmune disorders than to reverse them once established; a whole-food vegan diet, coupled with fish oil and vitamin D supplementation, may represent a practical strategy for achieving this prevention, while concurrently lowering risk for many other life-threatening 'Western' diseases.

Few population studies have measured urinary levels of pesticides in individuals with vegan, vegetarian, or organic diets. The objectives of this study were to evaluate whether a vegan/vegetarian diet was associated with increased exposure to organophosphate and carbamate pesticides, and to evaluate the impact of organic consumption on pesticide exposure in vegans and vegetarians. In the current pilot study conducted in 2013-2014, we collected spot urine samples and detailed 24h recall dietary data in 42 adult residents of Amirim, a vegetarian community in Northern Israel. We measured urinary levels of non-specific organophosphate pesticide metabolites (dialkylphosphates, (DAPs)) and specific metabolites of the current-use pesticides chlorpyrifos (3,5,6-trichloro-2-pyridinol (TCPy)), propoxur (-isopropoxyphenol (IPPX)), and carbaryl (1-naphthol). Six DAP metabolites were detected in between 67 and 100% of urine samples, with highest geometric mean concentrations for dimethylphosphate (19.2μg/g). Creatinine-adjusted median concentrations of total DAPs and of TCPy were significantly higher in Amirim residents compared to the general Jewish population in Israel (0.29μmol/g compared to 0.16, p<0.05 for DAPs and 4.32μg/g compared to 2.34μg/g, p<0.05 for TCPy). Within Amirim residents, we observed a positive association between vegetable intake and urinary TCPy levels (rho=0.47, p<0.05) and lower median total dimethyl phosphate levels in individuals reporting that>25% of the produce they consume is organic (0.065μmol/L compared to 0.22, p<0.05). Results from this pilot study indicate relatively high levels of urinary organophosphate pesticide metabolite concentrations in residents of a vegetarian community, a positive association between vegetable intake and urinary levels of a chlorpyrifos specific metabolite, and lower levels of total dimethyl phosphate in individuals reporting higher intake of organic produce. Results suggest that consumption of organic produce may offer some protection from increased exposure to organophosphate pesticide residues in vegetarians.

PURPOSE:GLUT-1 deficiency syndrome (GLUT1DS) is a neurologic disorder manifesting as epilepsy, abnormal movements, and cognitive delay. The currently accepted treatment of choice is the classic 4:1 ratio ketogenic diet.

METHODS:A 2-page survey was distributed to all attendees of a family-centered conference for GLUT1DS in July 2015. The surveys were completed by parents, collected anonymously, and information analyzed in a database.

RESULTS:Surveys were received from 92 families, of which 90 (98%) had been treated with dietary therapies. Diets used were extremely varied: 59 were treated with the classic ketogenic diet (KD), 29 with the Modified Atkins Diet (MAD), 4 with the Medium-chain Triglyceride (MCT) Diet and 2 with the low glycemic index treatment. The mean diet duration was 5.5 years (range: 1 month-20 years). Of those with seizures, 95% of the children had>50% seizure reduction and 80% had>90% seizure reduction. Children who were seizure-free were currently younger on average (8.2 vs. 11.6 years, p=0.01) and slightly younger at GLUT1DS diagnosis (3.8 vs. 5.3 years, p=0.05). There was an equal percentage of children seizure-free receiving the KD/MCT Diets compared to the MAD/Low Glycemic Index Treatment (74% vs. 63%, p=0.30). The majority (64%) were not receiving anticonvulsants.

CONCLUSION:This represents the largest series of KD experience in children with GLUT1DS. Nearly all patients surveyed were on dietary therapies for long durations with reported excellent seizure control, often without anticonvulsant drugs. Several different ketogenic diets were utilized with similar efficacy. Early diagnosis and treatment were correlated with success.

Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.

BACKGROUND:Pregnancy in women with advanced CKD becoming increasingly common. However, experience with low-protein diets in CKD patients in pregnancy is still limited. Aim of this study is to review the results obtained over the last 15 years with moderately restricted low-protein diets in pregnant CKD women (combining: CKD stages 3-5, proteinuria: nephrotic at any time, or > =1 g/24 at start or referral; nephrotic in previous pregnancy). CKD patients on unrestricted diets were employed for comparison.

METHODS:

STUDY PERIOD:January, 2000 to September, 2015: 36 on-diet pregnancies (31 singleton deliveries, 3 twin deliveries, 1 pregnancy termination, 1 miscarriage); 47 controls (42 singleton deliveries, 5 miscarriages). The diet is basically vegan; since occasional milk and yoghurt are allowed, we defined it vegan-vegetarian; protein intake (0.6-0.8 g/Kg/day), keto-acid supplementation, protein-unrestricted meals (1-3/week) are prescribed according to CKD stage and nutritional status. Statistical analysis was performed as implemented on SPSS.

RESULTS:Patients and controls were similar (p: ns) at baseline with regard to age (33 vs 33.5), referral week (7 vs 9), kidney function (CKD 3-5: 48.4 % vs 64.3 %); prevalence of hypertension (51.6 % vs 40.5 %) and proteinuria>3 g/24 h (16.1 % vs 12.2 %). There were more diabetic nephropathies in on-diet patients (on diet: 31.0 % vs controls 5.3 %; p 0.007 (Fisher)) while lupus nephropathies were non-significantly higher in controls (on diet: 10.3 % vs controls 23.7 %; p 0.28 (Fisher)). The incidence of preterm delivery was similar (<37 weeks: on-diet singletons 77.4 %; controls: 71.4 %). The incidence of other adverse pregnancy related outcomes was non-significantly lower in on-diet patients (early preterm delivery: on diet: 32.3 % vs controls 35.7 %; birth-weight = <1.500 g: on diet: 9.7 % vs controls 23.8 %). None of the singletons in the on-diet series died, while two perinatal deaths occurred among the controls (p = 0.505). The incidence of small for gestational age (SGA<10th centile) and/or extremely preterm babies (<28th week) was significantly lower in singletons from on-diet mothers than in controls (on diet: 12.9 % vs controls: 33.3 %; p: 0.04 (Fisher)).

CONCLUSION:Moderate protein restriction in the context of a vegan-vegetarian supplemented diet is confirmed as a safe option in the management of pregnant CKD patients.

Many patients with atopic dermatitis are dissatisfied with conventional treatments based on topical steroids and have experienced some traditional remedies and alternative therapies. However, most of such therapies have not been evaluated scientifically and clinically by specialists. This study was designed to assess whether a certain vegetarian diet might be effective for atopic dermatitis and if so, to identify the mechanisms of this remedy through analyses of immunological parameters. An open-trial study was carried out in twenty patients with atopic dermatitis. An improvement of dermatitis was evaluated by SCORAD index and serological and immunological parameters were monitored. After a two-month treatment, the severity of dermatitis was strikingly inhibited, as assessed by SCORAD index and serological parameters including LDH5 activity and a number of peripheral eosinophils. A sharp reduction in eosinophils and neutrophils was observed prior to improvement in the skin inflammation. In addition, PGE2 production by peripheral blood mononuclear cells was reduced by this treatment. In contrast, serum IgE levels did not change during the same period. Although this study is an open-trial one, it suggests that this treatment may be useful for the treatment of adult patients with severe atopic dermatitis.

Objective:Previous studies have reported that a vegetarian diet may lower blood pressure (BP), but the effect of diet on BP in asymptomatic participants with proteinuria is unknown. We examined the association of diet and BP in individuals with or without proteinuria.

Materials and Methods:This cross-sectional study analyzed data from participants who were more than 40 years old and received physical checkups at Taipei Tzu Chi Hospital from September 5, 2005, to December 31, 2016. Diets were assessed at baseline by a self-reported questionnaire and categorized as vegan, lacto-ovo vegetarian, or omnivore. There were 2818 (7.7%) vegans, 5616 (15.3%) lacto-ovo vegetarians, and 28,183 (77.0%) omnivores. The effect of different parameters on BP was determined using a multivariate multiple linear regression model with no intercept, with control for important characteristics and lifestyle confounders.

Results:The vegan group had a lower mean systolic BP (-3.87 mmHg,<0.001) and diastolic BP (-2.48 mmHg,<0.001) than the omnivore group. Participants with proteinuria had a higher systolic BP (4.26 mmHg,<0.001) and diastolic BP (2.15 mmHg,<0.001) than those without proteinuria. Interaction analysis indicated that vegan participants with proteinuria had a lower systolic BP (-2.73 mmHg,= 0.046) and diastolic BP (-2.54 mmHg,= 0.013) than other participants with proteinuria. However, individuals in the lacto-ovo group with proteinuria had a BP similar to other participants with proteinuria.

Conclusions:A vegan diet was associated with lower BP in asymptomatic participants with proteinuria. This diet could be a nonpharmacologic method to reduce BP.

AIM:The aim of this study was to investigate whether a vegetarian diet correlates with a potential reduced risk of uterine fibroids.

MATERIAL AND METHODS:We used data from a case-control study conducted in Southeast University Zhongda Hospital between February 2010 and December 2014. Cases included 600 Chinese Han women with uterine fibroids (case group) whose clinical diagnosis dated back no more than 1 year. Controls were 600 patients without uterine fibroids as well as healthy volunteers (control group). All of the information gathered through the questionnaire survey was analyzed for the risk factors of the uterine fibroids pathogenesis.

RESULTS:The multifactor analysis showed that women with uterine fibroids reported a less frequent consumption of broccoli (odds ratio [OR]: 0.552; 95% confidence interval [CI]: 0.316-0.964), cabbage (OR: 0.446; 95%CI: 0.211-0.943), Chinese cabbage (OR: 0.311; 95%CI: 0.102-0.946), tomato (OR: 0.453; 95%CI: 0.241-0.853), and apple (OR: 0.416; 95%CI: 0.213-0.814) (P<0.05).

CONCLUSION:The original evidence from this epidemiological investigation shows that a high consumption of broccoli, cabbage, Chinese cabbage, tomato and apple seems to be a protective factor for uterine fibroids. We suggest that greater intake of fresh fruits and cruciferous vegetables may be able to reduce the incidence of uterine fibroids.

Diabet. Med. 28, 549-559 (2011) ABSTRACT: Aims  The aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance, visceral fat and oxidative stress markers in subjects with Type 2 diabetes. Methods  A 24-week, randomized, open, parallel design was used. Seventy-four patients with Type 2 diabetes were randomly assigned to either the experimental group (n = 37), which received a vegetarian diet, or the control group (n = 37), which received a conventional diabetic diet. Both diets were isocaloric, calorie restricted(-500 kcal/day). All meals during the study were provided. The second 12 weeks of the diet were combined with aerobic exercise. Participants were examined at baseline, 12 weeks and 24 weeks. Primary outcomes were: insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp; volume of visceral and subcutaneous fat measured by magnetic resonance imaging; and oxidative stress measured by thiobarbituric acid reactive substances. Analyses were by intention to treat. Results  Forty-three per cent of participants in the experimental group and 5% of participants in the control groupreduced diabetes medication (P < 0.001). Body weight decreased more in the experimental group than in the control group [-6.2 kg (95% CI -6.6 to -5.3) vs. -3.2 kg (95% CI -3.7 to -2.5); interaction group × time P = 0.001]. An increase in insulin sensitivity was significantly greater in the experimental groupthan in the control group [30% (95% CI 24.5-39) vs. 20% (95% CI 14-25), P = 0.04]. A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group (P = 0.007 and P = 0.02, respectively). Plasma adiponectin increased (P = 0.02) and leptin decreased (P = 0.02) in the experimental group, with no change in the control group. Vitamin C, superoxide dismutase and reduced glutathione increased in the experimental group (P = 0.002, P < 0.001 and P = 0.02, respectively). Differences between groups were greater after the addition of exercise training. Changes in insulin sensitivity and enzymatic oxidative stress markers correlated with changes in visceral fat. Conclusions  A calorie-restricted vegetarian diet had greater capacity to improve insulin sensitivity compared with a conventional diabetic diet over 24 weeks. The greater loss of visceral fat and improvements in plasma concentrations of adipokines and oxidative stress markers with this diet may be responsible for the reduction of insulin resistance. The addition of exercise training further augmented the improved outcomes with the vegetarian diet.

OBJECTIVES:A vegetarian diet may prevent elevation of blood pressures and lower the risk for hypertension through lower degrees of obesity, inflammation, and insulin resistance. This study investigated the association between a vegetarian diet and hypertension incidence in a cohort of Taiwanese adult nonsmokers and examined whether this association was mediated through inflammation, abdominal obesity, or insulin resistance (using fasting glucose as a proxy).

METHODS:This matched cohort study was from the 1994-2008 MJ Health Screening Database. Each vegetarian was matched with five nonvegetarians by age, sex, and study site. The analysis included 4109 nonsmokers (3423 nonvegetarians and 686 vegetarians), followed for a median of 1.61 years. The outcome includes hypertension incidence, as well as SBP and DBP levels. Regression analysis was performed to assess the association between vegetarian diet and hypertension incidence or future blood pressure levels in the presence/absence of potential mediators.

RESULTS:Vegetarians had a 34% lower risk for hypertension, adjusting for age and sex (odds ratio: 0.66, 95% confidence interval: 0.50-0.87; SBP: -3.3 mmHg, P < 0.001; DBP: -1.5 mmHg, P < 0.001). The results stay statistically significant after further adjustment for C-reactive protein, waist circumference, and fasting glucose (odds ratio: 0.72, 95% confidence interval: 0.55-0.86; SBP: -2.4 mmHg, P < 0.05; DBP: -1.1 mmHg, P < 0.05). The protective association between vegetarian diet and hypertension appeared to be consistent across age groups.

CONCLUSION:Taiwanese vegetarians had lower incidence of hypertension than nonvegetarians. Vegetarian diets may protect against hypertension beyond lower abdominal obesity, inflammation, and insulin resistance.

BACKGROUND/OBJECTIVES:Vegetarian diets are inversely associated with diabetes in Westerners but their impact on Asians-whose pathophysiology differ from Westerners-is unknown. We aim to investigate the association between a vegetarian diet, change in dietary patterns and diabetes risk in a Taiwanese Buddhist population.

METHODS:We prospectively followed 2918 non-smoking, non-alcohol drinking Buddhists free of diabetes, cancer, and cardiovascular diseases at baseline, for a median of 5 years, with 183 incident diabetes cases confirmed. Diet was assessed through a validated food frequency questionnaire at baseline and a simple questionnaire during follow-ups. Incident cases of diabetes were ascertained through follow-up questionnaires, fasting glucose and HbA1C. Stratified Cox Proportional Hazards Regression was used to assess the effect of diets on risk of diabetes.

RESULTS:Consistent vegetarian diet was associated with 35% lower hazards (HR: 0.65, 95% CI: 0.46, 0.92), while converting from a nonvegetarian to a vegetarian pattern was associated with 53% lower hazards (HR: 0.47, 95% CI: 0.30, 0.71) for diabetes, comparing with nonvegetarians while adjusting for age, gender, education, physical activity, family history of diabetes, follow-up methods, use of lipid-lowering medications, and baseline BMI.

CONCLUSION:Vegetarian diet and converting to vegetarian diet may protect against diabetes independent of BMI among Taiwanese.

Cardiovascular (CV) disease (CVD) is the leading global cause of mortality, being responsible for 46% of non-communicable disease deaths. It has been estimated that about 85.6 million Americans are living with some form of CVD, which continues to rise. Healthy lifestyle choices may reduce the risk of myocardial infarction by>80%, with nutrition playing a key role. Vegetarian dietary patterns reduce CVD mortality and the risk of coronary heart disease (CHD) by 40%. Plant-based diets are the only dietary pattern to have shown reversal of CHD. Additionally, evidence suggests benefits of vegetarian dietary patterns in both the prevention and the treatment of heart failure and cerebrovascular disease. Plant-based diets are associated with lower blood pressure, lower blood lipids, and reduced platelet aggregation than non-vegetarian diets and are beneficial in weight management, reduce the risk of developing metabolic syndrome, and type 2 diabetes. They have also been shown an effective treatment method in diabetes management. Well planned vegetarian diets provide benefits in preventing and reversing atherosclerosis and in decreasing CVD risk factors and should be promoted through dietary guidelines and recommendations.

While dietary restriction of protein intake has long been proposed as a possible kidney-protective treatment, the effects of changes in the quality of ingested proteins on the prevalence and risk of progression of chronic kidney disease (CKD) have been scarcely studied; these two aspects are reviewed in the present article. The prevalence of hypertension, type 2 diabetes and metabolic syndrome, which are the main causes of CKD in Western countries, is lower in vegetarian populations. Moreover, there is a negative relationship between several components of plant-based diets and numerous factors related to CKD progression such as uraemic toxins, inflammation, oxidative stress, metabolic acidosis, phosphate load and insulin resistance. In fact, results from different studies seem to confirm a kidney-protective effect of plant-based diets in the primary prevention of CKD and the secondary prevention of CKD progression. Various studies have determined the nutritional safety of plant-based diets in CKD patients, despite the combination of a more or less severe dietary protein restriction. As observed in the healthy population, this dietary pattern is associated with a reduced risk of all-cause mortality in CKD patients. We propose that plant-based diets should be included as part of the clinical recommendations for both the prevention and management of CKD.

BACKGROUND:Beneficial effects of vegetarian and vegan diets on health outcomes have been supposed in previous studies.

OBJECTIVES:Aim of this study was to clarify the association between vegetarian, vegan diets, risk factors for chronic diseases, risk of all-cause mortality, incidence and mortality from cardio-cerebrovascular diseases, total cancer and specific type of cancer (colorectal, breast, prostate and lung), through meta-analysis.

METHODS:A comprehensive search of Medline, EMBASE, Scopus, The Cochrane Library and Google Scholar was conducted.

RESULTS:Eighty-six cross-sectional and 10 cohort prospective studies were included. The overall analysis among cross-sectional studies reported significant reduced levels of body mass index, total cholesterol, LDL-cholesterol, and glucose levels in vegetarians and vegans versus omnivores. With regard to prospective cohort studies, the analysis showed a significant reduced risk of incidence and/or mortality from ischemic heart disease (RR 0.75; 95% CI, 0.68 to 0.82) and incidence of total cancer (RR 0.92; 95% CI 0.87 to 0.98) but not of total cardiovascular and cerebrovascular diseases, all-cause mortality and mortality from cancer. No significant association was evidenced when specific types of cancer were analyzed. The analysis conducted among vegans reported significant association with the risk of incidence from total cancer (RR 0.85; 95% CI, 0.75 to 0.95), despite obtained only in a limited number of studies.

CONCLUSIONS:This comprehensive meta-analysis reports a significant protective effect of a vegetarian diet versus the incidence and/or mortality from ischemic heart disease (-25%) and incidence from total cancer (-8%). Vegan diet conferred a significant reduced risk (-15%) of incidence from total cancer.

Paroxysmal visual manifestations may represent epileptic seizures arising from the occipital lobe. In coeliac disease (CD) bilateral occipital calcifications and seizure semiology consistent with an occipital origin have been described, primarily in Mediterranean countries. By reporting three adult patients from an Australian outpatient clinic with visual disturbances, occipital cerebral calcifications, and CD, this study seeks to emphasise that CD should be considered even when patients of non-Mediterranean origin present with these symptoms. Seizure types included simple partial, complex-partial, and secondarily generalised seizures. The seizure semiology consisted of visual disturbances such as: blurred vision, loss of focus, seeing coloured dots, and brief stereotyped complex visual hallucinations like seeing unfamiliar faces or scenes. Symptoms of malabsorption were not always present. Neurological examination was unremarkable in two patients, impaired dexterity and mild hemiatrophy on the left was noted in one. Routine electroencephalography was unremarkable. In all cases, computed tomography demonstrated bilateral cortical calcification of the occipital-parietal regions. Magnetic resonance imaging showed no additional lesion. All patients had biopsy confirmed CD. Seizure control improved after treatment with gluten free diet and anticonvulsants. This report illustrates the association between seizures of occipital origin, cerebral calcifications, and CD even in patients not of Mediterranean origin.

Observational studies have found a protective effect of vitamin C on cardiovascular health. However, results are inconsistent, and residual confounding by fiber might be present. The aim of this study was to assess the association of vitamin C with the incidence of cardiovascular disease (CVD) and cardiovascular mortality (CVM) while accounting for fiber intake and adherence to the Mediterranean dietary pattern. We followed up 13,421 participants in the Seguimiento Universidad de Navarra (University of Navarra follow-up) (SUN) cohort for a mean time of 11 years. Information was collected at baseline and every two years through mailed questionnaires. Diet was assessed with a validated semi-quantitative food frequency questionnaire. Incident CVD was defined as incident fatal or non-fatal myocardial infarction, fatal or non-fatal stroke, or death due to any cardiovascular cause. CVM was defined as death due to cardiovascular causes. Events were confirmed by physicians in the study team after revision of medical records. Cox proportional hazard models were fitted to assess the associations of (a) energy-adjusted and (b) fiber-adjusted vitamin C intake with CVD and CVM. We found energy-adjusted vitamin C was inversely associated with CVD and CVM after adjusting for several confounding factors, including fiber from foods other than fruits and vegetables, and adherence to the Mediterranean dietary pattern. On the other hand, when vitamin C was adjusted for total fiber intake using the residuals method, we found a significant inverse association with CVM (HR (95% confidence interval (CI)) for the third tertile compared to the first tertile, 0.30 (0.12-0.72), but not with CVD in the fully adjusted model.

BACKGROUND: Trials comparing the effectiveness and safety of weight-loss diets are frequently limited by short follow-up times and high dropout rates.

METHODS: In this 2-year trial, we randomly assigned 322 moderately obese subjects (mean age, 52 years; mean body-mass index [the weight in kilograms divided by the square of the height in meters], 31; male sex, 86%) to one of three diets: low-fat, restricted-calorie; Mediterranean, restricted-calorie; or low-carbohydrate, non-restricted-calorie.

RESULTS: The rate of adherence to a study diet was 95.4% at 1 year and 84.6% at 2 years. The Mediterranean-diet group consumed the largest amounts of dietary fiber and had the highest ratio of monounsaturated to saturated fat (P<0.05 for all comparisons among treatment groups). The low-carbohydrate group consumed the smallest amount of carbohydrates and the largest amounts of fat, protein, and cholesterol and had the highest percentage of participants with detectable urinary ketones (P<0.05 for all comparisons among treatment groups). The mean weight loss was 2.9 kg for the low-fat group, 4.4 kg for the Mediterranean-diet group, and 4.7 kg for the low-carbohydrate group (P<0.001 for the interaction between diet group and time); among the 272 participants who completed the intervention, the mean weight losses were 3.3 kg, 4.6 kg, and 5.5 kg, respectively. The relative reduction in the ratio of total cholesterol to high-density lipoprotein cholesterol was 20% in the low-carbohydrate group and 12% in the low-fat group (P=0.01). Among the 36 subjects with diabetes, changes in fasting plasma glucose and insulin levels were more favorable among those assigned to the Mediterranean diet than among those assigned to the low-fat diet (P<0.001 for the interaction among diabetes and Mediterranean diet and time with respect to fasting glucose levels).

CONCLUSIONS: Mediterranean and low-carbohydrate diets may be effective alternatives to low-fat diets. The more favorable effects on lipids (with the low-carbohydrate diet) and on glycemic control (with the Mediterranean diet) suggest that personal preferences and metabolic considerations might inform individualized tailoring of dietary interventions. (ClinicalTrials.gov number, NCT00160108.)