Vitamin D insufficiency and disease risk in the elderly.

Vitamin D insufficiency, milder than deficiency, is common, and a risk of various diseases. Since vitamin D exert diverse actions, both skeletal and non-skeletal, its insufficiency is a risk of various diseases including osteoporosis, sarcopenia, cardiovascular disease, cancer, and even mortality. Regarding the association of vitamin D status and disease risk, a marked discrepancy exists between the results from the observational studies and intervention studies, mostly yielding the positive and negative results in the former and latter, respectively. Such inconsistency probably arises from methodological problems, of which the baseline vitamin D status would be the most important. Vitamin D intervention would be effective in the deficient/insufficient subjects, but not in sufficient subjects. Since the elderly subjects, especially the institutionalized people, are mostly vitamin D deficient/insufficient, they are likely to benefit from improvement of vitamin D status. Vitamin insufficiency is a risk of various diseases, and correcting the vitamin status alone would reduce the risk of many diseases, and favorable to avoid the undesirable consequences of polypharmacy in the elderly. Additionally, disease prevention by nutritional improvement is cheap and free from side effects, and suited for the primary prevention of diseases.

High prevalence of vitamin B-12 deficiency before and early after gastrectomy in patients with gastric cancer.

BACKGROUND AND OBJECTIVES: Gastrectomy causes vitamin B-12 deficiency since vitamin B-12 requires gastric acid and intrinsic factor for its absorption. Vitamin B-12 deficiency is considered to develop years after gastrectomy because of large hepatic storage. However, most gastric cancer develops after long-standing atrophic gastritis with vitamin B-12 malabsorption. METHODS AND STUDY DESIGN: We have investigated vita-min B-12 status in 22 patients before gastrectomy and 53 patients after gastrectomy due to gastric cancer, also with consideration on post-gastrectomy anemia. RESULTS: Blood vitamin B-12, folic acid, homocysteine concentrations, parameters of anemia, and dietary intake were evaluated. Percentage of patients with severe vitamin B-12 deficiency (serum vitamin B-12 < 150 pmol/L), vitamin B-12 deficiency (150 pmol/L to < 258 pmol/L) was 19.0 %, and 52.4 % respectively in patients gastrectomized within three years. Before gastrectomy, three and seven patients exhibited severe deficiency and deficiency, respectively. In gastrectomized patients, plasma homocysteine concentration was inversely associated with serum vitamin B-12 concentration, and vitamin B-12 deficiency- and iron deficiency- anemia coexisted with their mean corpuscular volume within the reference range. CONCLUSIONS: Vitamin B-12 deficiency is prevalent in patients early after and before gastrectomy. Coexistence of vitamin B-12 and iron deficiency obscures the diagnosis of post-gastrectomy anemia, and necessitates the blood vitamin B-12 measurement.

Vitamin D deficiency as the risk of respiratory tract infections in the institutionalized elderly: A prospective 1-year cohort study.

BACKGROUND & AIMS: Respiratory tract infections (RTIs) are one of the major causes of morbidity and mortality in the elderly. Since vitamin D is known to play important roles in immunity, and its deficiency has been reported to be prevalent in the elderly, we have studied the relationship between serum 25-hydroxyvitamin D [25(OH)D] level, which is the most reliable marker for vitamin D status, and the incidence of RTIs in the institutionalized elderly by a prospective observational study. METHODS: From 208 Japanese subjects aged 60 and older fulfilling the inclusion criteria, 148 subjects remained after propensity score matching. Data were obtained from the medical records including their age, gender, histories of co-morbidities and medications, the incidence of acute RTIs including pneumonia. Measurement of serum 25(OH)D level and assessment of nutrients intake including vitamin D were done at baseline. Cox's proportional hazard analysis was performed to assess the significant predictors for RTIs during the follow-up period. RESULTS: The median observation duration was 354.2 days, and the incidence of RTIs was 75.8 person-years. Subjects with RTIs had significantly lower serum 25(OH)D concentration, and a higher prevalence of vitamin D deficiency (25(OH)D < 10 ng/mL). Cox's proportional hazard analysis revealed that vitamin D deficiency was a significant predictor for RTIs. CONCLUSIONS: Our results suggested that vitamin D deficiency was a significant predictor for an increased incidence of RTIs in institutionalized elderly, and the necessity of vitamin D supplementation for the prevention of RTIs was considered.

Insufficiency of B vitamins with its possible clinical implications.

Vitamin deficiency causes classical deficiency diseases such as beriberi and rickets. Vitamin insufficiency, which is milder than deficiency, is a risk for various chronic diseases, but its significance has not been recognized in Japan. Vitamin D insufficiency is quite common in Japan, and a serious risk for osteoporotic fracture through its unbeneficial effect on bone and muscle. Insufficiency of B vitamins has been little studied. However, hyperhomocysteinemia caused by the insufficiency of vitamin B12 or folate is a risk for cardiovascular disease, osteoporotic fracture, and cognitive impairment. Additionally, we have recently reported that vitamin B1 insufficiency is a risk for heart failure in the elderly. The effect of improvement of nutritional status including vitamins is less marked compared to drug treatment, but it costs far less, and is suited for the primary prevention of diseases. Randomized controlled trial is considered the study with the most robust evidence in the evaluation of drug treatment, but more emphasis should be put on the well-designed cohort studies in evaluating the role of nutrients. Vitamin insufficiency is quite prevalent, and vitamin requirement is much higher for its prevention than for the prevention of deficiency.

Diversity of Gut Microbiota Affecting Serum Level of Undercarboxylated Osteocalcin in Patients with Crohn's Disease.

Several reports have indicated a possible link between decreasing plasma levels of vitamin K and bone mineral density. It has been suggested that intestinal bacteria contribute to maintenance of vitamin K. Several factors are involved in the reduction of vitamin K in patients with Crohn's disease (CD). We aimed to assess the relationship between gut microbiota and alternative indicators of vitamin K deficiency in patients with CD. We collected the feces of 26 patients with clinically inactive CD. We extracted 16S rRNA from the intestinal bacteria in the feces and amplified it by polymerase chain reaction. The generated polymerase chain reaction product was analyzed using a 16S metagenomic approach by Illumina Miseq platform. Serum undercarboxylated osteocalcin concentration was used as an alternative indicator of vitamin K deficiency. There was a significant negative correlation between serum undercarboxylated osteocalcin and mean Chao1 index in cases of low activity. The diversity of the gut microbiota was significantly lower, and Ruminococcaceae and Lachnospiraceae were significantly decreased in the vitamin K-deficient group in comparison to the vitamin K-normal group. Taken together, these data suggested the significance of investigating the gut microbiota even in patients with clinically inactive CD for improving patients' vitamin K status.

Possible involvement of thiamine insufficiency in heart failure in the institutionalized elderly.

Heart failure is a major manifestation of thiamine deficiency; beriberi. Even thiamine insufficiency, milder than deficiency, may be associated with increased heart failure risk. In this cross-sectional study, the relationship between thiamine insufficiency and heart failure was investigated in the Japanese institutionalized elderly from April to November 2017. Fifty-five subjects in four care facilities were evaluated for their whole blood thiamine and plasma brain natriuretic peptide concentrations. Mean whole blood thiamine concentration was 88.7 ± 22.3 nmol/L in men and 92.0 ± 16.5 nmol/L in women, and significantly and negatively correlated with plasma brain natriuretic peptide concentrations (r = -0.378, p = 0.007). In the multiple regression analysis adjusted by age, sex, body mass index, and eGFR, whole blood thiamine concentration was a significant negative contributor (standardized coefficient ß = -0.488, p = 0.001) to plasma brain natriuretic peptide. In the logistic regression analysis adjusted by the same variables, whole blood thiamine concentration significantly contributed to plasma brain natriuretic peptide concentration higher than over 40 pg/ml (OR: 0.898, 95%CI: 0.838-0.962). Whole blood thiamine concentration in subjects with diuretics was significantly lower than those without it (p = 0.023). Thiamine insufficiency was related to increased plasma brain natriuretic peptide concentration and may increase the risk of heart failure.

Relationship between Homocysteine, Folate, Vitamin B12 and Physical Performance in the Institutionalized Elderly.

Hyperhomocysteinemia causes various diseases including cardiovascular disease, osteoporotic fracture and dementia. Although there have been reports that hyperhomocysteinemia decreases physical performance, findings are inconsistent on the association of homocysteine, folate, vitamin B12 and physical performance. Considering that lower physical performance increases the risk of fall and fracture in the elderly, the effect of nutritional status on physical function must be clarified. This is a cross-sectional study conducted from April 2015 to November 2016. Eighty-six residents and users in five care facilities were evaluated for their blood homocysteine, folate and vitamin B12 concentrations and indices for physical performance; lower limb muscle strength, handgrip strength and gait speed. Analyses of physical performance were done in women only, considering the high proportion of women in the study population and the muscular gender difference. In the third tertile of plasma homocysteine concentration, handgrip strength was significantly lower than in the first tertile (p=0.027). In the first tertile of serum folate concentration, handgrip strength was significantly lower than in the third tertile (p=0.002). Although not statistically significant, lower limb muscle strength in the third tertile of folate was higher than in the first (p=0.061) and second (p=0.057) tertile. In the multiple regression analysis, however, only serum folate concentration was a significant contributor except for age. In subjects with their serum folate and vitamin B12 concentrations both exceeding the median, lower limb muscle strength was higher. Low serum folate concentration is a risk factor for lower physical performance independent of homocysteine in elderly women.

Gastric and Jejunal Enteral Feeding Differently Affect Vitamin B12 Status in Subjects with Severe Motor and Intellectual Disabilities.

The absorption of vitamin B12 is a complex process involving gastric acid and intrinsic factor as the indispensable components. In this study, we have investigated the effects of the administration site in enteral feeding on vitamin B12 status in subjects with severe motor and intellectual disabilities (SMID). This is a cross-sectional study conducted from January to June 2016. Blood concentrations of vitamin B12, folate, vitamin B6, and homocysteine (Hcy) were measured in a total of 82 subjects (38 men, 44 women). Also, nutrients intake was assessed. Subjects with enteral feeding (EF) had significantly higher intakes of vitamin B12, folate, and vitamin B6 than those with oral ingestion (OI). Serum folate and vitamin B6 concentrations in subjects with EF were significantly higher than those with OI. Among the EF subjects, serum vitamin B12 concentration was significantly higher in those fed with gastric tube than those fed with jejunal tube in spite of similar vitamin B12 intakes. No significant difference was observed between the two groups regarding the circulating concentrations of folate, vitamin B6, or Hcy. Although each administration route has its own benefit, gastric tube is advantageous in the absorption of vitamin B12.

High prevalence of vitamin B-12 insufficiency in patients with Crohn's disease.

BACKGROUND AND OBJECTIVES: In Crohn's disease (CD), belonging to inflammatory bowel disease, the small intestine is involved in most cases. Most frequently affected is the distal ileum, where vitamin B-12 is specifically absorbed. Therefore, malabsorption of vitamin B-12 is quite likely to occur in patients with CD. In this study, we have studied the vitamin B-12 status in CD patients. METHODS AND STUDY DESIGN: Forty eight patients with CD were evaluated for their food intake, and circulating concentrations of vitamin B-12, folic acid, and homocysteine (Hcy) as a sensitive marker for the insufficiency of these vitamins and a risk factor of atherosclerosis. RESULTS: Plasma Hcy concentration was significantly correlated with serum vitamin B-12 concentration alone, and 60.4 % of the subjects had hyperhomocysteinemia. Receiver Operating Characteristics (ROC) analysis showed that serum concentration of vitamin B-12, but not folic acid, predicted hyperhomocysteinemia. Their intake of vitamin B-12 was much higher than the Japanese RDA, but not correlated with blood concentrations of vitamin B-12 or Hcy, probably due to malabsorption. CONCLUSIONS: Vitamin B-12 insufficiency and hyperhomocysteinemia were highly prevalent in CD patients. Recently, the significance of extra-intestinal complications of CD has been increasingly recognized, and our finding is likely to be of clinical importance.

Associations between serum 25-hydroxyvitamin D3 level and skeletal muscle mass and lower limb muscle strength in Japanese middle-aged subjects.

OBJECTIVES: One of the important risk factors of falling is decreased muscle mass and muscle strength. Recently, there has been an increasing concern on the role of vitamin D in muscle strength and physical activity. Aim of our study is to examine the relationships between vitamin D status and muscle mass and muscle strength in middle-aged healthy adults. METHODS: Subjects were 40 healthy volunteers aged 42.0 ± 10.6 years old. Evaluation was made for serum vitamin D3 metabolites including 25-hydroxyvitamin D3 [25(OH)D3] and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] concentrations, lower limb muscle strength, and dietary intake by food frequency questionnaire. Body composition was measured by dual-energy X-ray absorptiometry (DXA), and appendicular skeletal mass index (ASMI) was calculated as skeletal muscle mass/squared height. RESULTS: 70% of the subjects had vitamin D insufficiency/deficiency (serum total 25(OH)D < 20 ng/mL), and female subjects had significantly lower serum total 25(OH)D level compared with males. Vitamin D insufficiency/deficiency group had significantly higher body fat, lower SMI and muscle strength, probably reflecting higher percentage of female subjects. Serum vitamin D3 metabolites levels were significantly correlated with whole and site-specific ASMI, and lower limb muscle strength, except for the correlation between serum 24,25(OH)2D3 concentration and lower limb muscle strength. In addition, serum 25(OH)D3 level was a positive significant predictor for both ASMI and lower limb muscle strength, while serum 24,25(OH)2D3 level was not their significant predictor. CONCLUSIONS: Serum 25(OH)D3 level was significantly correlated with both skeletal muscle mass and lower limb muscle strength.

Comparison of lower leg muscle strength and grip strength for diagnosing slower gait speed in the elderly.

OBJECTIVES: Sarcopenia, decreased muscle volume and muscle weakness in the elderly is a serious risk of various adverse outcomes. Current diagnostic procedure for sarcopenia includes gait speed, grip strength, and percentage of skeletal muscle volume. However, lower leg muscle strength decreases much faster than grasp power, and we have evaluated the usefulness of its measurement using a recently developed instrument (Locomoscan). METHODS: Forty-three institutionalized elderly subjects were evaluated for their anthropometrical parameters, body composition, grasp and lower leg muscle strength, and gait speed. They were categorized into 2 groups; gait speed equal to or higher than 0.8 m/s and that below 0.8 m/s. RESULTS: Leg muscle strength per body weight was significantly greater in those with their gait speed equal to or higher than 0.8 m/s, whereas there was no significant difference in other parameters. Receiver operator characteristics analysis has shown that leg muscle alone significantly predicted the greater gait speed. CONCLUSIONS: Lower leg muscle strength can be useful for predicting gait speed.