Estimating Vitamin C Intake Requirements in Diabetes Mellitus: Analysis of NHANES 2017-2018 and EPIC-Norfolk Cohorts.

Vitamin C is an essential enzyme cofactor and antioxidant with pleiotropic roles in human physiology. Circulating vitamin C concentrations are lower in people with diabetes mellitus, suggesting a higher dietary requirement for the vitamin. We interrogated the NHANES 2017-2018 and EPIC-Norfolk datasets to compare vitamin C requirements between those with and without diabetes mellitus using dose-concentration relationships fitted with sigmoidal (four-parameter logistic) curves. The NHANES cohort (n = 2828 non-supplementing adults) comprised 488 (17%) participants with diabetes (self-reported or HbA1c ≥ 6.5%). The participants with diabetes had a lower vitamin C status (median [IQR]) than those without (38 [17, 52] µmol/L vs. 44 [25, 61] µmol/L, p < 0.0001), despite comparable dietary intakes between the two groups (51 [26, 93] mg/d vs. 53 [24, 104] mg/d, p = 0.5). Dose-concentration relationships indicated that the group without diabetes reached adequate vitamin C concentrations (50 µmol/L) with an intake of 81 (72, 93) mg/d, whilst those with diabetes required an intake of 166 (126, NA) mg/d. In the EPIC-Norfolk cohort, comprising 20692 non-supplementing adults, 475 (2.3%) had self-reported diabetes at baseline. The EPIC cohort had a lower BMI than the NHANES cohort (26 [24, 28] kg/m2 vs. 29 [25, 34] kg/m2, p < 0.0001). Correspondingly, the EPIC participants without diabetes required a lower vitamin C intake of 64 (63, 65) mg/d while those with diabetes required 129 (104, NA) mg/d to reach adequate circulating vitamin C status. C-reactive protein concentrations were strongly correlated with body weight and BMI and provided a surrogate biomarker for vitamin C requirements. In conclusion, people with diabetes had 1.4 to 1.6 fold higher requirements for vitamin C than those without diabetes. This corresponds to additional daily vitamin C intake requirements of ~30-40 mg for people with diabetes, equating to a total daily intake of at least 125 mg/d.

Long-term effects of gestational diabetes on bone mineral density and fracture risk: Analysis of the Norfolk cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk) population-based study.

OBJECTIVES: Gestational diabetes mellitus (GDM) is a common pregnancy complication. This study aims to investigate the association between a history of GDM and bone mineral density (BMD), fractures, and falls in later life. STUDY DESIGN: We used data from the Norfolk cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk) where BMD at calcaneum was measured at second health check (1997-2000) using broadband ultrasound attenuation (BUA) and velocity of sound (VOS) in 7,515 women. Fractures and falls were documented from hospital admissions data via linkage with ENCORE (East Norfolk Commission Record) and history of GDM from health questionnaires at baseline. We examined the relationship between GDM and BUA/VOS using linear regression. Cox regression was used to estimate hazard ratios (HRs) for incident fractures and falls, controlling for age, BMI, smoking status, physical activity, area deprivation, self-reported stroke, use of diuretics, calcium and vitamin D supplements, social class and education, statin and total blood cholesterol, prevalent diabetes, hormone therapy and menopausal status. RESULTS: History of GDM (n = 183) was not statistically significantly associated with BUA/VOS in fully adjusted linear regression models with unstandardised beta coefficients (standard error): -0.37 (1.40) and -5.41 (3.48). GDM was significantly (p < 0.05) associated with risk of hip and all fractures, fully adjusted HRs(95 %CI) 2.46(1.54-3.92) and 1.60(1.09-2.35), respectively. Median follow-up from first live birth to date of admission was 53 and 52 years, respectively. CONCLUSION: There was an association between history of GDM and risk of any fracture as well as hip fracture specifically. Further research is required to confirm this.

Self-Reported Fatigue Predicts Incident Stroke in a General Population: EPIC-Norfolk Prospective Population-Based Study.

Background and Purpose- Fatigue is a common symptom among stroke survivors and in general practice. However, the clinical significance of fatigue and its relationship to incident stroke is unclear. The aim of this study was to examine the relationship between self-reported fatigue and the incidence of stroke in a general population. Methods- This was a prospective, population-based study. The study population was 15 654 men and women aged 39 to 79 years recruited in 1993 to 1997 and followed till March 2016. Fatigue was assessed at 18 months after baseline using the vitality domain of the Short Form 36 questionnaire. Cox proportional hazard models were constructed to describe the prospective relationship between baseline fatigue and incident stroke adjusting for age, sex, systolic blood pressure, cholesterol, physical activity, smoking status, alcohol consumption, fruit and vegetable consumption, diabetes mellitus, body mass index, vitamin supplement use, education level, Townsend deprivation index, and occupational social class. Incident stroke was ascertained using death certificates and hospital record linkage data. Results- Through 249 248 person-years of follow-up, 1509 incident strokes occurred. Participants who reported the highest level of fatigue (quartile 4) were more likely to be women, to be multimorbid, and to perceive their health as fair or poor. We observed ≈50% relative risk increase in stroke risk (hazard ratio, 1.49 [95% CI, 1.29-1.71]) in those who reported the highest level of fatigue compared with those who reported the lowest level of fatigue (Q4 versus Q1). This relationship remained unaltered regardless of anemia status, the presence or absence of chronic bronchitis, thyroid dysfunction, or depression. Conclusions- Self-report fatigue assessed by the vitality domain of the Short Form 36 questionnaire predicts the risk of future stroke at the general population level. Identifying and addressing stroke risk factors in those who report fatigue in general practice may have substantial benefit at the population level.

Variability in the clinical management of iron deficiency anaemia in older adults: results from a survey of UK specialists in the care of older people.

BACKGROUND: Iron deficiency anaemia in older adults is common, but its management presents unique challenges in diagnosis and management. Little is known about compliance with current best practice guidelines. METHODS: We undertook an online survey of physician members of the British Geriatrics Society to ascertain how they managed older patients with potential iron deficiency anaemia. RESULTS: There were 141 respondents (96% from UK). Almost a third indicated they would accept haemoglobin levels <100 g/dl without further investigation. A quarter said they would only occasionally or never check ferritin levels. Only 30% would sometimes or always use parenteral iron when oral supplements were not tolerated. CONCLUSIONS: Responses suggest a high level of variation in clinical practice and low adherence to best practice guidelines. Possible explanations include an inadequate evidence base to guide management and a lack of knowledge on the challenges of managing iron deficiency anaemia in this population.

Effect of nonmeat, high-protein supplementation on quality of life and clinical outcomes in older residents of care homes: a systematic review and meta-analysis.

Context: Care home residents are at risk of malnutrition owing to reduced food intake, anabolic resistance in aging muscle, and a high prevalence of medical morbidity and functional dependency. There has been limited consensus regarding the effectiveness of a high-protein diet on quality of life or clinical outcomes in care home residents. Objective: The aim of this review was to evaluate the effectiveness of nonmeat, high-protein supplementation on health-related quality of life (HRQOL) and relevant clinical and nutritional outcomes in older people in a care home setting. Data Sources: The following databases were searched (to February 2018) for randomized controlled trials: Embase, AMED, CINAHL, MEDLINE, the Cochrane Central Registry of Controlled Trials, OpenGrey, clinicaltrials.gov, the WHO International Clinical Trials Registry Platform, the ISRCTN registry, and the NIHR Clinical Research Network Portfolio. Study Selection: Trials were selected if they assessed a nonmeat, high-protein dietary intervention provided to care home residents who were aged 65 years or older. Data Extraction: Data from included trials were extracted if they assessed care home residents aged 65 years or older and compared those residents who received protein supplementation with those who did not. Trial quality was assessed using the Cochrane risk-of-bias tool. Meta-analysis was undertaken when appropriate. Results: Seventeen studies with 1246 participants fulfilled the inclusion criteria. All studies were of low or moderate quality. There was no evidence of improved HRQOL when the Short Form 36 (SF-36) was used to assess outcomes (standardized mean difference [SMD] = -0.10; 95%CI, -0.51 to 0.31; P = 0.62), although significant improvement was seen in the 1 trial that used the EQ-5D instrument (SMD = 2.58; 95%CI, 2.05-3.10; P < 0.00001). Conclusions: Nonmeat, high-protein oral supplements can improve markers of nutritional status in care home residents. However, there is insufficient high-quality evidence to determine the effect of such supplements on HRQOL in older adults in care homes. Systematic Review Registration: PROSPERO registration number: CRD42015029313.

Nutritional supplementation for hip fracture aftercare in older people.

BACKGROUND: Older people with hip fractures are often malnourished at the time of fracture, and subsequently have poor food intake. This is an update of a Cochrane review first published in 2000, and previously updated in 2010. OBJECTIVES: To review the effects (benefits and harms) of nutritional interventions in older people recovering from hip fracture. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, CENTRAL, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, Embase, CAB Abstracts, CINAHL, trial registers and reference lists. The search was last run in November 2015. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of nutritional interventions for people aged over 65 years with hip fracture where the interventions were started within the first month after hip fracture. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, extracted data and assessed risk of bias. Where possible, we pooled data for primary outcomes which were: all cause mortality; morbidity; postoperative complications (e.g. wound infections, pressure sores, deep venous thromboses, respiratory and urinary infections, cardiovascular events); and 'unfavourable outcome' defined as the number of trial participants who died plus the number of survivors with complications. We also pooled data for adverse events such as diarrhoea. MAIN RESULTS: We included 41 trials involving 3881 participants. Outcome data were limited and risk of bias assessment showed that trials were often methodologically flawed, with less than half of trials at low risk of bias for allocation concealment, incomplete outcome data, or selective reporting of outcomes. The available evidence was judged of either low or very low quality indicating that we were uncertain or very uncertain about the estimates.Eighteen trials evaluated oral multinutrient feeds that provided non-protein energy, protein, vitamins and minerals. There was low-quality evidence that oral feeds had little effect on mortality (24/486 versus 31/481; risk ratio (RR) 0.81 favouring supplementation, 95% confidence interval (CI) 0.49 to 1.32; 15 trials). Thirteen trials evaluated the effect of oral multinutrient feeds on complications (e.g. pressure sore, infection, venous thrombosis, pulmonary embolism, confusion). There was low-quality evidence that the number of participants with complications may be reduced with oral multinutrient feeds (123/370 versus 157/367; RR 0.71, 95% CI 0.59 to 0.86; 11 trials). Based on very low-quality evidence from six studies (334 participants), oral supplements may result in lower numbers with 'unfavourable outcome' (death or complications): RR 0.67, 95% CI 0.51 to 0.89. There was very low-quality evidence for six studies (442 participants) that oral supplementation did not result in an increased incidence of vomiting and diarrhoea (RR 0.99, 95% CI 0.47 to 2.05).Only very low-quality evidence was available from the four trials examining nasogastric multinutrient feeding. Pooled data from three heterogeneous trials showed no evidence of an effect of supplementation on mortality (14/142 versus 14/138; RR 0.99, 95% CI 0.50 to 1.97). One trial (18 participants) found no difference in complications. None reported on unfavourable outcome. Nasogastric feeding was poorly tolerated. One study reported no cases of aspiration pneumonia.There is very low-quality evidence from one trial (57 participants, mainly men) of no evidence for an effect of tube feeding followed by oral supplementation on mortality or complications. Tube feeding, however, was poorly tolerated.There is very low-quality evidence from one trial (80 participants) that a combination of intravenous feeding and oral supplements may not affect mortality but could reduce complications. However, this expensive intervention is usually reserved for people with non-functioning gastrointestinal tracts, which is unlikely in this trial.Four trials tested increasing protein intake in an oral feed. These provided low-quality evidence for no clear effect of increased protein intake on mortality (30/181 versus 21/180; RR 1.42, 95% CI 0.85 to 2.37; 4 trials) or number of participants with complications but very low-quality and contradictory evidence of a reduction in unfavourable outcomes (66/113 versus 82/110; RR 0.78, 95% CI 0.65 to 0.95; 2 trials). There was no evidence of an effect on adverse events such as diarrhoea.Trials testing intravenous vitamin B1 and other water soluble vitamins, oral 1-alpha-hydroxycholecalciferol (vitamin D), high dose bolus vitamin D, different oral doses or sources of vitamin D, intravenous or oral iron, ornithine alpha-ketoglutarate versus an isonitrogenous peptide supplement, taurine versus placebo, and a supplement with vitamins, minerals and amino acids, provided low- or very low-quality evidence of no clear effect on mortality or complications, where reported.Based on low-quality evidence, one trial evaluating the use of dietetic assistants to help with feeding indicated that this intervention may reduce mortality (19/145 versus 36/157; RR 0.57, 95% CI 0.34 to 0.95) but not the number of participants with complications (79/130 versus 84/125). AUTHORS' CONCLUSIONS: There is low-quality evidence that oral multinutrient supplements started before or soon after surgery may prevent complications within the first 12 months after hip fracture, but that they have no clear effect on mortality. There is very low-quality evidence that oral supplements may reduce 'unfavourable outcome' (death or complications) and that they do not result in an increased incidence of vomiting and diarrhoea. Adequately sized randomised trials with robust methodology are required. In particular, the role of dietetic assistants, and peripheral venous feeding or nasogastric feeding in very malnourished people require further evaluation.

Iron status in the elderly.

Iron deficiency anaemia is prevalent in older age, particularly after the age of 80. Serum ferritin concentrations also decline, although there is no evidence to suggest that changes in iron stores are an inevitable consequence of ageing. Chronic inflammation is a common condition in older people, making the measurement of iron status difficult, and it is likely that elevated levels of circulating hepcidin are responsible for changes in iron metabolism that result in systemic iron depletion. Other contributory factors are poor diet and some medications, such as aspirin. Anaemia in older age has undesirable health outcomes, including increased susceptibility to falling and depression. However, there are concerns about possible adverse effects of iron supplements, either in relation to pro-inflammatory effects in the gut or inappropriate tissue iron deposition. Brain iron levels are increased with age-related degenerative diseases, but it is not known if this is the cause or a consequence of the disease, and genetic factors are likely to play a role. In order to maintain body iron within the normal range a personalised approach is required, taking into account all of the factors that may affect iron metabolism and the available strategies for preventing iron deficiency or overload.

Association between plasma vitamin C concentrations and blood pressure in the European prospective investigation into cancer-Norfolk population-based study.

The effect of fruit and vegetable consumption and blood pressure is unclear. A population-based cross-sectional study was conducted in 20 926 men and women aged 40 to 79 years participating in the European Prospective Investigation Into Cancer-Norfolk who completed a health questionnaire and attended a clinic from 1993 to 1997. The relationship between plasma vitamin C concentrations, as an indicator of fruit and vegetable intake, and systolic BP was examined. The magnitude of their association was assessed using dichotomized values of high (≥140 mm Hg) and low (<140 mm Hg) systolic blood pressure. A total of 20 926 participants (46% men; mean [SD] 58.5 years [9.2 years]) were included after excluding participants with any missing data for variables of interest. People with high vitamin C concentrations had lower clinic blood pressure. The likelihood of having high blood pressure was 22% lower (odds ratio: 0.78 [95% CI: 0.71 to 0.86]) for those who were in the top quartiles of plasma vitamin C levels compared with the bottom quartiles after adjusting for age, sex, body mass index, cholesterol, prevalent medical conditions, smoking, physical activity, alcohol consumption, social class, education, use of vitamin C-containing supplement, and antihypertensive medication. Sex-specific analysis, as well as repeated analysis after exclusion of people who used vitamin C-containing supplements or who were taking antihypertensive medication, did not alter the results. There appears to be a strong association between vitamin C concentrations, an indicator of fruit and vegetable consumption, and a lower level of blood pressure. This may provide further evidence for health benefits of dietary patterns with higher fruit and vegetable consumption.

Plasma vitamin C concentrations predict risk of incident stroke over 10 y in 20 649 participants of the European Prospective Investigation into Cancer Norfolk prospective population study.

BACKGROUND: The relation between plasma vitamin C and risk of stroke remains unclear. Although clinical trials showed no significant benefit of vitamin C supplementation in reducing stroke risk, they were not able to examine the relation between plasma vitamin C concentrations and stroke risk in a general population. OBJECTIVE: The objective was to examine the relation between baseline plasma vitamin C concentrations and risk of incident stroke in a British population. DESIGN: A population-based prospective study was conducted in 20,649 men and women aged 40-79 y without prevalent stroke at baseline and participating in the European Prospective Investigation into Cancer-Norfolk prospective population study. The participants completed a health questionnaire and attended a clinic during 1993-1997 and were followed up for incident strokes through March 2005. RESULTS: Over 196,713 total person-years (average follow-up: 9.5 y), 448 incident strokes occurred. In a Cox proportional hazards model, persons in the top quartiles of baseline plasma vitamin C concentrations had a 42% lower risk (relative risk: 0.58; 95% CI: 0.43, 0.78) than did those in the bottom quartile, independently of age, sex, smoking, body mass index, systolic blood pressure, cholesterol, physical activity, prevalent diabetes and myocardial infarction, social class, alcohol consumption, and any supplement use. Similar results were obtained after exclusion of persons with illnesses, users of ascorbic acid-containing supplements, and persons with a history of early strokes during the initial 2 y of follow-up. CONCLUSIONS: Plasma vitamin C concentrations may serve as a biological marker of lifestyle or other factors associated with reduced stroke risk and may be useful in identifying those at high risk of stroke.

Habitual fish consumption and risk of incident stroke: the European Prospective Investigation into Cancer (EPIC)-Norfolk prospective population study.

OBJECTIVES: To examine the association between fish consumption and stroke risk. DESIGN: Prospective population cohort study. SETTING: Norfolk, UK cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk). SUBJECTS: Subjects were 24 312 men and women aged 40-79 years who had no previous history of stroke at baseline. METHODS: Fish consumption was assessed using a food-frequency questionnaire at baseline in 1993-1997 and stroke incidence ascertained to 2004. RESULTS: A total of 421 incident strokes were identified (mean follow-up=8.5 years, total person-years=209 238). There were no significant relationships between total fish, shellfish or fish roe consumption and risk of stroke in men and women after adjusting for age, systolic blood pressure, body mass index, smoking, cholesterol, diabetes, physical activity, alcohol consumption, fish oil supplement use and total energy intake using Cox regression analyses. Oily fish consumption was significantly lower in women who subsequently had a stroke (odds ratio (OR) for consumers vs. non-consumers=0.69, 95% confidence interval (CI) 0.51-0.94, P=0.02). The trend in men was similar but not significant (OR for consumers vs. non-consumers=0.88, 95% CI 0.65-1.19, P=0.41). CONCLUSIONS: There was no consistent relationship between fish consumption and stroke in this British population. Inconsistencies in the observed health effects of fish consumption in different populations may reflect different patterns and type of fish consumed and preparation methods.