Life Extension Magazine®

Issue: Jan 2016

Oral health, Alpha cyclodextrin, Proton pump, Immune senescence, and Vitamin D

Oral health, Alpha cyclodextrin, Proton pump, Immune senescence, and Vitamin D

By Life Extension.

Oral health

Association of periodontal diseases and liver fibrosis in patients with HCV and/or HBV infection.

BACKGROUND: Periodontal disease and systemic health are closely associated. However, there is no data supporting the association between periodontal disease and patients with liver diseases associated with hepatitis C virus (HCV) and/or hepatitis B virus (HBV) infection. OBJECTIVES: The aim of this study was to evaluate the association between periodontitis and progression of liver diseases in patients with HCV and/or HBV infection. PATIENTS AND METHODS: In this retrospective study, 351 patients with HCV- and/or HBV-related liver diseases underwent screening for periodontal disease using the Salivaster® salivary occult blood test from February 2010 to June 2014. Furthermore, we examined the prevalence of fimbrillin (fimA) genotype of Porphyromonas gingivalis (P. gingivalis) in 28 HCV-infected patients visited at our hospital between January 2013 and June 2014. P. gingivalis with fimA genotype with types I to V was further detected using a PCR method. RESULTS: Of 351 patients, 76 patients (group 1) had a strong positive result for salivary occult blood test and 275 patients (group 2) had weak positive or negative test results. Significant factors between the groups were obesity, level of AST, ALT, LDH, ALP, Alb, D.Bil, T.cho, AFP, platelets (Plt), IRI, HOMA-IR, current interferon (IFN) treatment and the daily frequency of tooth brushing. Between-groups analysis indicated that total protein ( level and liver fibrosis were significant factors. According to multivariate analysis, five factors were associated with periodontal disease as Plt count below 80000, brushing teeth only once a day, current IFN treatment, aged 65 years or older and obesity. The adjusted odds ratios for these five factors were 5.80, 3.46, 2.87, 2.50 and 2.33, respectively, and each was statistically significant. Twenty-eight saliva specimens had positive results for P. gingivalis with fimA genotype types I to V. The prevalence of fimA genotype II was higher in 14 patients with liver cirrhosis or a history of hepatocellular carcinoma treatment (group B, 50.00%) than 14 patients with only hepatitis C (group A, 21.43%). CONCLUSIONS: Periodontitis might be associated with progression of viral liver disease; hence, controlling oral disease is essential for the prevention and management of liver fibrosis.

Hepat Mon. 2014 Dec 20;14(12):e23264

Involvement of a periodontal pathogen, Porphyromonas gingivalis on the pathogenesis of non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome that is closely associated with multiple factors such as obesity, hyperlipidemia and type 2 diabetes mellitus. However, other risk factors for the development of NAFLD are unclear. With the association between periodontal disease and the development of systemic diseases receiving increasing attention recently, we conducted this study to investigate the relationship between NAFLD and infection with Porphyromonas gingivalis (P. gingivalis), a major causative agent of periodontitis. METHODS: The detection frequencies of periodontal bacteria in oral samples collected from 150 biopsy-proven NAFLD patients (102 with non-alcoholic steatohepatitis (NASH) and 48 with non-alcoholic fatty liver (NAFL) patients) and 60 non-NAFLD control subjects were determined. Detection of P. gingivalis and other periodontopathic bacteria were detected by PCR assay. In addition, effect of P. gingivalis-infection on mouse NAFLD model was investigated. To clarify the exact contribution of P. gingivalis-induced periodontitis, non-surgical periodontal treatments were also undertaken for 3 months in 10 NAFLD patients with periodontitis. RESULTS: The detection frequency of P. gingivalis in NAFLD patients was significantly higher than that in the non-NAFLD control subjects (46.7% vs. 21.7%, odds ratio: 3.16). In addition, the detection frequency of P. gingivalis in NASH patients was markedly higher than that in the non-NAFLD subjects (52.0%, odds ratio: 3.91). Most of the P. gingivalis fimbria detected in the NAFLD patients was of invasive genotypes, especially type II (50.0%). Infection of type II P. gingivalis on NAFLD model of mice accelerated the NAFLD progression. The non-surgical periodontal treatments on NAFLD patients carried out for 3 months ameliorated the liver function parameters, such as the serum levels of AST and ALT. CONCLUSIONS: Infection with high-virulence P. gingivalis might be an additional risk factor for the development/progression of NAFLD/NASH.

BMC Gastroenterol. 2012 Feb 16;12:16

Periodontal disease is associated with renal insufficiency in the Atherosclerosis Risk In Communities (ARIC) study.

BACKGROUND: Periodontitis, a chronic bacterial infection of the oral cavity, is a novel risk factor for atherosclerotic cardiovascular disease (CVD). Given the numerous shared risk factors for CVD and chronic kidney disease (CKD), we hypothesized that periodontitis also is associated with renal insufficiency in the Dental Atherosclerosis Risk in Communities study. METHODS: We conducted a cross-sectional study of 5,537 middle-aged black and white men and women. Periodontitis was determined by using an independent clinically derived definition and categorized as healthy/gingivitis, initial, and severe. Renal insufficiency is defined as glomerular filtration rate (GFR) less than 60 mL/min/1.73 m2 . Multivariable logistic regression models were used to estimate odds ratios and 95% confidence intervals for renal insufficiency using healthy/gingivitis as the referent group. RESULTS: A total of 2,276 individuals had initial periodontitis, and 947 individuals had severe periodontal disease. One hundred ten individuals (2%) had a GFR less than 60 mL/min/1.73 m2. Compared with healthy/gingivitis, initial and severe periodontal disease were associated with a GFR less than 60 mL/min/1.73 m2 (odds ratio, 2.00; 95% confidence interval, 1.23 to 3.24) for initial periodontal disease and an odds ratio of 2.14 for severe disease (95% confidence interval, 1.19 to 3.85) after adjustment for important risk factors for CVD and CKD. Sensitivity analysis showed that initial and severe periodontitis were each associated with an elevated serum creatinine level (men, >1.4 mg/dL [>124 micromol/L]; women, >1.2 mg/dL [>106 micromol/L]; odds ratio, 3.21; 95% confidence interval, 1.32 to 7.76 and odds ratio, 5.39; 95% confidence interval, 2.08 to 13.99, respectively). CONCLUSION: This is the first study to show an association of periodontal disease with prevalent renal insufficiency. A prospective study is necessary to determine the exact nature of the observed relationship.

Am J Kidney Dis. 2005 Apr;45(4):650-7

Bidirectional relationship between chronic kidney and periodontal disease: a study using structural equation modeling.

Periodontal disease is associated with diabetes, heart disease, and chronic kidney disease (CKD), relationships postulated to be due in part to vascular inflammation. A bidirectional relationship between CKD and periodontal disease is plausible, though this relationship has not been previously reported. In this study, we assessed the potential for connections between CKD and periodontal disease, and mediators of these relationships using structural equation models of data from 11,211 adults ≥ 18 years of age who participated in the Third National Health and Nutrition Examination Survey. Multivariable logistic regression models were used to test the hypothesis that periodontal disease was independently associated with CKD. Given the potential that the periodontal disease and CKD relationship may be bidirectional, a two-step analytic approach was used that involved tests for mediation and structural equation models to examine more complex direct and indirect effects of periodontal disease on CKD, and vice versa. In two separate models, periodontal disease (adjusted odds ratio of 1.62), edentulism (adjusted odds ratio of 1.83), and the periodontal disease score were associated with CKD when simultaneously adjusting for 14 other factors. Altogether, three of four structural equation models support the hypothesized relationship. Thus, our analyses support a bidirectional relationship between CKD and periodontal disease, mediated by hypertension and the duration of diabetes.

Kidney Int. 2011 Feb;79(3):347-55

Current understanding of the relationship between periodontal and systemic diseases.

Periodontal disease (PD) is among the most common infectious diseases affecting humans. While the burden of periodontal disease on oral health has been extensively investigated, a possible specific relationship between the disease and systemic health is a relatively new area of interest. More recently it has been suggested that PD has an etiological role in the development of atherosclerotic cardiovascular disease, diabetes mellitus, and preterm low-birth weight, among others. In this review, we critically evaluate the current knowledge on the relation between PD and systemic diseases overall, and specifically with cardiovascular diseases. The best available evidence today suggests that the infection and inflammatory reaction associated with PD may contribute toward systemic disease. It is critical that dentists and physicians are well informed of the potential general health impact of periodontal disease so that they are in a position to knowledgeably counsel patients.

Saudi Med J. 2015 Feb;36(2):150-8

Acquiring and maintaining a normal oral microbiome: current perspective.

The oral microbiota survives daily physical and chemical perturbations from the intake of food and personal hygiene measures, resulting in a long-term stable microbiome. Biological properties that confer stability in the microbiome are important for the prevention of dysbiosis-a microbial shift toward a disease, e.g., periodontitis or caries. Although processes that underlie oral diseases have been studied extensively, processes involved in maintaining of a normal, healthy microbiome are poorly understood. In this review we present our hypothesis on how a healthy oral microbiome is acquired and maintained. We introduce our view on the prenatal development of tolerance for the normal oral microbiome: we propose that development of fetal tolerance toward the microbiome of the mother during pregnancy is the major factor for a successful acquisition of a normal microbiome. We describe the processes that influence the establishment of such microbiome, followed by our perspective on the process of sustaining a healthy oral microbiome. We divide microbiome-maintenance factors into host-derived and microbe-derived, while focusing on the host. Finally, we highlight the need and directions for future research.

Front Cell Infect Microbiol. 2014 Jun 26;4:85

Probiotics and oral health.

Probiotics are living microorganisms (e.g., bacteria) that are either the same as or similar to organisms found naturally in the human body and may be beneficial to health. Current researches have shown that the balance between beneficial and pathogenic bacteria is essential in order to maintain the oral health. Therefore, oral cavity has recently been suggested as a relevant target for probiotic applications. Dental caries can be seen as a microbial imbalance where the oral microbiota shift towards community dominance which produces acidogenic and acid-tolerant gram positive bacteria. Similarly, the accumulation of bacteria within the biofilm, facilitated by poor oral hygiene, predisposes to allogenic shifts in the microbial community, leading to the onset of periodontal inflammation. Probiotic bacteria belonging to the genus of Lactobacillus, Bifidobacterium and Streptococcus have been proven effective for preventing caries by reducing the number of cariogenic bacteria in saliva after a short period of consuming the probiotic. In contrast, the effect of probiotics on improving gingivitis and periodontitis has been less investigated. The currently available studies on the effect of probiotics on periodontal pathogens and clinical periodontal parameters showed differing results depending on the strains used and the endpoints analyzed. Many of the clinical studies are pilot in nature and with low quality, therefore, properly conducted clinical trials, using probiotic strains with in vitro proven periodontal probiotic effects, are needed. The putative beneficial effects of probiotics on oral malodour have also been evaluated, but further evidence is needed to fully explore the potential of probiotics for preventing malodour.

Curr Pharm Des. 2012;18(34):5522-31

Probiotics as oral health biotherapeutics.

INTRODUCTION: Oral health is affected by its resident microorganisms. Three prominent oral disorders are dental caries, gingivitis and periodontitis, with the oral microbiota playing a key role in the initiation/progression of all three. Understanding the microbiota and the diseases they may cause is critical to the development of new therapeutics. This review is focused on probiotics for the prevention and/or treatment of oral diseases. AREAS COVERED: This review describes the oral ecosystem and its correlation with oral health/disease. The pathogenesis and current prevention/treatment strategies of periodontal diseases (PD) and dental caries (DC) are depicted. An introduction of probiotics is followed by an analysis of their role in PD and DC, and their potential role(s) in oral health. Finally, a discussion ensues on the future research directions and limitations of probiotics for oral health. EXPERT OPINION: An effective oral probiotic formulation should contribute to the prevention/treatment of microbial diseases of the oral cavity. Understanding the oral microbiota’s role in oral disease is important for the development of a therapeutic to prevent/treat dental diseases. However, investigations into clinical efficacy, delivery/dose optimization, mechanism(s) of action and other related parameters are yet to be fully explored. Keeping this in mind, investigations into oral probiotic therapies are proving promising.

Expert Opin Biol Ther. 2012 Sep;12(9):1207-20

Alpha cyclodextrin

Dose-dependent inhibition of the post-prandial glycaemic response to a standard carbohydrate meal following incorporation of alpha-cyclodextrin.

BACKGROUND: This study evaluated the dose-response effects of alpha-cyclodextrin, a cyclic oligosaccharide, on the glycaemic and insulinaemic responses to the consumption of a standard carbohydrate meal. METHODS: In a double-blind, randomised, cross-over design, 10 healthy subjects consumed boiled white rice containing 50 g of digestible carbohydrate to which 0 (control), 2, 5 or 10 g of alpha-cyclodextrin was added. Plasma glucose and insulin concentrations were determined prior to and for 2 h after consumption of each meal. RESULTS: The area under the plasma glucose curve was negatively related to the dose of alpha-cyclodextrin (r(2)=0.97, p=0.02), with the areas being significantly reduced at the 5- and 10-gram doses compared with the control (p<0.05). alpha-Cyclodextrin did not affect the area under the plasma insulin curve (p=0.39). Higher doses of alpha-cyclodextrin resulted in greater satiety, but were associated with reduced palatability and an increased incidence of minor gastrointestinal complaints (stomach ache, nausea, bloating). CONCLUSION: alpha-Cyclodextrin reduces the glycaemic response to a standard carbohydrate meal in a dose-dependent manner and may be useful as an ingredient for reducing the glycaemic impact of such foods.

Ann Nutr Metab. 2006;50(2):108-14

Nutritional significance of cyclodextrins: indigestibility and hypolipemic effect of alpha-cyclodextrin.

Digestibility of alpha- and beta-cyclodextrin (CD) and nutritional consequences of alpha-CD and a CD mixture (n-dextrin, alpha-, beta-and gamma-CDs = 50, 30, 15 and 5% by weight) were investigated in rats. In contrast with beta-CD, alpha-CD was revealed to be indigestible. Growing rats were fed on diets supplemented with the CD mixture at 19.5, 39, 58.5 and 78% levels for 110 days, resulting in smaller weight gain and body fat deposition when they were fed on a higher CD diet. Rates of weight loss during the restricted feeding were faster in rats fed on a higher CD diet. These were due to food efficiency lowered by CD. Reduced serum and liver triacylglycerol (TG) levels were noted during a 110-day period of feeding of the CD diets, and the former was revealed due to a reduced hepatic-intestinal TG secretion rate. Rats fed on a 78% CD diet, which contained alpha-CD at the 24% level, showed abnormal symptoms such as poor appetite and constipation with gas accumulation in the large intestine, and some of them died during the first 2-week feeding period. However, the surviving animals showed adaptation to the diet in the later period of the 110-day feeding. These results suggest that alpha-CD may be classified as dietary fiber which can modulate lipid metabolism in rats. Furthermore, the CD mixture may be available as a calorie substitute for weight control, which may owe mostly to alpha-CD.

J Nutr Sci Vitaminol (Tokyo). 1985 Apr;31(2):209-23

Dietary alpha-cyclodextrin lowers low-density lipoprotein cholesterol and alters plasma fatty acid profile in low-density lipoprotein receptor knockout mice on a high-fat diet.

High dietary intake of saturated fat and cholesterol, and elevated low-density lipoprotein cholesterol levels are some of the modifiable risk factors for cardiovascular disease. Alpha-cyclodextrin (a-CD) when given orally has been shown in rats to increase fecal saturated fat excretion and to reduce blood total cholesterol levels in obese hypertriglyceridemic subjects with type 2 diabetes mellitus. In this study, the effects of dietary a-CD on lipid metabolism in low-density lipoprotein receptor knockout mice were investigated. Low-density lipoprotein receptor knockout mice were fed a “Western diet” (21% milk fat) with or without 2.1% of a-CD (10% of dietary fat content) for 14 weeks. At sacrifice, there was no difference in body weight; but significant decreases were observed in plasma cholesterol (15.3%), free cholesterol (20%), cholesterol esters (14%), and phospholipid (17.5%) levels in mice treated with alpha-CD compared with control mice. The decrease in total cholesterol was primarily in the proatherogenic apolipoprotein B-containing lipoprotein fractions, with no significant change in the high-density lipoprotein fraction. Furthermore, alpha-CD improved the blood fatty acid profile, reducing the saturated fatty acids (4.5%) and trans-isomers (11%) while increasing (2.5%) unsaturated fatty acids. In summary, the addition of alpha-CD improved the lipid profile by lowering proatherogenic lipoproteins and trans-fatty acids and by decreasing the ratio of saturated and trans-fatty acids to polyunsaturated fatty acids (-5.8%), thus suggesting that it may be useful as a dietary supplement for reducing cardiovascular disease.

Metabolism. 2008 Aug;57(8):1046-51

Health habits and other characteristics of dietary supplement users: a review.

Dietary supplements are used by half to two-thirds of American adults, and the evidence suggests that this usage is one component of a larger effort to develop a healthier lifestyle. Dietary supplement users tend on average to be better educated and to have somewhat higher incomes than nonusers, and these factors may contribute to their health-consciousness. Dietary supplement use also tends to be more prevalent among women than among men, and the prevalence of use increases with age in both men and women. Numerous surveys document that users of dietary supplements are significantly more likely than nonusers to have somewhat better dietary patterns, exercise regularly, maintain a healthy weight, and avoid tobacco products. While supplement users tend to have better diets than nonusers, the differences are relatively small, their diets have some substantial nutrient shortfalls, and their supplement use has been shown to improve the adequacy of nutrient intakes. Overall, the evidence suggests that users of dietary supplements are seeking wellness and are consciously adopting a variety of lifestyle habits that they consider to contribute to healthy living.

Nutr J. 2014 Feb 6;13:14

The effects of a new soluble dietary fiber on weight gain and selected blood parameters in rats.

This study was designed to investigate a new dietary fiber, alpha-cyclodextrin, marketed under the trade name FBCx (Wacker Biochem, Adrian, MI), for beneficial effects on weight reduction and the improvement of certain blood parameters in rats. Male Wistar rats were divided into 4 groups and fed ad libitum for a period of 6 weeks: (1) a normal low-fat diet (LF; 4% fat wt/wt); (2) an LF diet with FBCx added; (3) a high-fat diet (HF, 40% fat wt/wt); and (4) an HF diet with FBCx. The FBCx was added at the rate of 10% (wt/wt) of the fat in the diet. Body weight and food intake were recorded 3 times per week. Plasma constituent levels and liver and fecal lipid contents, as well as body composition were determined at sacrifice. Adding FBCx to the diet significantly reduced weight gain in rats fed with an HF diet relative to rats fed with the HF control diet (P < .05). FBCx also elicited a reduction in plasma triglyceride levels of 30%, total cholesterol of 9%, and increased the fat content of the feces in the rats fed with the HF diet with FBCx. In addition, the serum leptin levels were normalized, and the calculated insulin sensitivity was improved. No adverse effects were observed in the rats consuming FBCx. It would appear that FBCx might be effective in reducing body weight gain and improving metabolic syndrome.

Metabolism. 2006 Feb;55(2):195-202

The benefits of early intervention in obese diabetic patients with FBCx: a new dietary fibre.

BACKGROUND: Obesity and diabetes have become epidemic in the US. Dietary fibres have been reported to reduce the absorption of dietary fat, prevent weight gain, and reduce blood lipid levels. In the current double-blind study, obese patients with type 2 diabetes were recruited for a 3-month study to examine the health effects of a new dietary fibre, FBCx. METHODS: Sixty-six participants were recruited and were randomized into FBCx or placebo groups. They were instructed to take two 1-g tablets per fat-containing meal and not to change their eating patterns or daily routine. Three-day dietary records and fasting blood samples were collected prior to enrollment in the study and at the end of months 1, 2 and 3. RESULTS: Dietary records showed that some participants changed their eating patterns; therefore body weight data were adjusted according to energy intake. As a group, in the 30 days leading into the study, all participants experienced an average weight gain of 1.0 +/- 0.4 kg, while those in the placebo group continued to gain weight during the study, those in the FBCx group maintained their weight. Those in the FBCx group required more energy to maintain their body weight while those in the placebo group required less (p < 0.05). Participants with hypertriglyceridemia showed a reduction (-0.48 +/- 0.24 mmol/L, - 8.2%) in total cholesterol with FBCx, while those with placebo had an increase (0.24 +/- 0.21 mmol/L, 5.2%, p < 0.05). Adiponectin was increased in the FBCx but reduced in the placebo group (p < 0.05). CONCLUSIONS: FBCx has thus shown promising benefits in weight maintenance, a reduction of blood lipids and an increase in adiponectin levels. It can be easily incorporated into a diabetic management regimen.

Diabetes Metab Res Rev. 2007 Jan;23(1):56-62

The beneficial effects of a-cyclodextrin on blood lipids and weight loss in healthy humans.

a-Cyclodextrin (a-CD) is a soluble fiber derived from corn. It has previously been reported that early intervention with Mirafit fbcx, a trademarked name for a-CD, has beneficial effects on weight management in obese individuals with type 2 diabetes, and that it preferentially reduces blood levels of saturated and trans fats in the LDL receptor knockout mice. The current investigation involves overweight but not obese nondiabetic individuals and was intended to confirm the effects of a-CD on both weight management and improving blood lipid levels. Forty-one healthy adults (age: 41.4 ± 13.6 years) participated in this 2-month, double-blinded, crossover study. In 28 compliant participants (8 males and 20 females), when the active phase was compared to the control phase, there were significant decreases in body weight (-0.4 ± 0.2 kg, P < 0.05), serum total cholesterol (mean ± s.e.m., -0.295 ± 0.10 mmol/l, 5.3%, P < 0.02) and low-density lipoprotein (LDL) cholesterol (-0.23 ± 0.11 mmol/l, -6.7%, P < 0.05). Apolipoprotein B (Apo B) (-0.0404 ± 0.02 g/l, -5.6%, P = 0.06) and insulin levels also decreased by 9.5% (-0.16 ± 0.08 pmol/l, P = 0.06) while blood glucose and leptin levels did not change. These results suggest that a-CD exerts its beneficial health effects on body weight and blood lipid profile in healthy nonobese individuals, as previously reported in obese individuals with type 2 diabetes.

Obesity (Silver Spring). 2011 Jun;19(6):1200-4

Proton pump

Severe hypomagnesaemia in long-term users of proton pump inhibitors.

OBJECTIVE: To explore the mechanism underlying severe hypomagnesaemia in long-term users of proton-pump inhibitors (PPIs). PATIENTS: Two cases of severe hypomagnesaemia in adult long-term users of the PPI omeprazole, presenting with hypocalcaemic seizures. MEASUREMENTS: We studied renal magnesium handling during an incremental intravenous magnesium infusion, and assessed total body magnesium status by the 24-h retention of the parenteral load. We also observed the effects of oral magnesium supplements whilst continuing the PPI, and the effect of withdrawal of the PPI. RESULTS: Both patients were severely magnesium-depleted and had avid renal magnesium retention, implicating a failure of intestinal magnesium absorption. There was no evidence of generalized malabsorption. The hypomagnesaemia could be partially corrected by high dose oral magnesium supplementation, and resolved on withdrawal of PPIs. CONCLUSIONS: PPI use can inhibit active magnesium transport in the intestine, though it is not clear if this is an idiosyncratic effect. Long-term PPI users who are highly adherent to treatment can eventually deplete total body magnesium stores and present with severe complications of hypomagnesaemia.

Clin Endocrinol (Oxf). 2008

A case series of proton pump inhibitor-induced hypomagnesemia.

Proton pump inhibitor (PPI)-induced hypomagnesemia has been recognized since 2006. Our aim was to further characterize the clinical consequences and possible mechanisms of this electrolyte disorder using 4 cases. Two men (aged 63 and 81 years) and 2 women (aged 73 and 62 years) had been using a PPI (esomeprazole, pantoprazole, omeprazole, and rabeprazole, 20-40 mg) for 1-13 years. They developed severe hypomagnesemia (magnesium, 0.30 +/- 0.28 mEq/L; reference, 1.40-2.10 mEq/L) with hypocalcemia (calcium, 6.4 +/- 1.8 mg/dL), relative hypoparathyroidism (parathyroid hormone, 43 +/- 6 pg/mL), and extremely low urinary calcium and magnesium excretion. One patient was admitted with postanoxic encephalopathy after a collapse likely caused by arrhythmia. The others had electrocardiogram abnormalities (prolonged QT interval, ST depression, and U waves). Concomitant hypokalemia (potassium, 2.8 +/- 0.1 mEq/L) was considered the trigger for these arrhythmias. Hypomagnesemia-induced kaliuresis (potassium excretion, 65 +/- 24 mEq/L) was identified as the cause of hypokalemia. This series of PPI-induced hypomagnesemia shows that this is a generic effect. It also indicates that hypomagnesemia may occur within 1 year of PPI therapy initiation and can have serious clinical consequences, likely triggered by the associated hypokalemia. A high index of suspicion is required in PPI users for unexplained hypomagnesemia, hypocalcemia, hypokalemia, or associated symptoms.

Am J Kidney Dis. 2010 Jul;56(1):112-6

Hypomagnesaemia due to use of proton pump inhibitors—a review.

Magnesium homeostasis is essential for many intracellular processes and depends on the balance of intestinal absorption and renal excretion. Hypomagnesaemia may arise from various disorders. We review the literature on hypomagnesaemia due to the use of proton pump inhibitors, as illustrated by a case of a 76-year-old woman with muscle cramps and lethargy caused by hypomagnesaemia and hypocalcaemia with a low parathyroid hormone level while using esomeprazole, a proton pump inhibitor (PPI). After oral magnesium repletion both abnormalities resolved. Fractional magnesium excretion was low, excluding excessive renal loss. A causal relation with PPI use was supported by the recurrence of hypomagnesaemia after rechallenge. In the past decade our understanding of transcellular magnesium transport was enhanced by the discovery of several gene mutations i.e. transient receptor potential melastin (TR PM) 6 and 7. In this light we discuss the possible aetiology of proton pump inhibitor related hypomagnesaemia.

Neth J Med. 2009 May;67(5):169-72

Hypomagnesaemia due to proton pump inhibitor therapy: a clinical case series.

BACKGROUND: Reports since 2006 have identified proton-pump inhibitor (PPI) therapy as a cause of hypomagnesaemia, in a total of 13 cases. AIMS: To summarize the clinical course of 10 patients (one male, nine female) identified with severe hypomagnesaemia, all of whom were on PPI therapy. A case report illustrates the experience of a severely affected patient. METHODS: Clinical and biochemical review. Severe hypomagnesaemia was defined as 0.54 mmol/l or less, >4 SD below the mean. RESULTS: Patients were 68.8 +/- 8.6 years old when they presented with severe hypomagnesaemia, having been on PPI therapy for a mean of 8.3 +/- 3.5 years. Eight patients were on diuretics at initial presentation. There was significant morbidity as eight patients remained on PPI therapy after presentation for a mean of 2.75 +/- 1.54 years. There were 18 emergency hospital admissions with severe hypomagnesaemia. Oral and parenteral magnesium supplements were relatively ineffective at correcting the problem, but stopping PPI therapy lead to prompt resolution of the hypomagnesaemia (within 2 weeks in five carefully monitored patients), with symptomatic benefit. Hypomagnesaemia recurred if PPI therapy was re-introduced because of troublesome dyspepsia. However, pantoprazole, the least potent PPI, largely relieved dyspepsia and hypomagnesaemia did not inevitably develop when combined with oral magnesium supplements. CONCLUSION: These cases confirm that long-term PPI therapy can cause severe, symptomatic hypomagnesaemia, which resolves when PPI therapy is withdrawn. The serum magnesium should be checked annually in patients on long-term PPI therapy, or if they feel unwell.

QJM. 2010 Jun;103(6):387-95

Proton pump inhibitors, osteoporosis, and osteoporosis-related fractures.

Proton pump inhibitors (PPIs) are among the most commonly prescribed medications today with an excellent short-term safety profile. Recently, a number of studies from a variety of data sources have reported an association between PPI use and hip fractures. However, there is not yet any direct evidence of a causal link between PPI use and the development of hip fracture. In the following paper, we will review the recent studies which have described this association between PPI use and hip fracture, and discuss the evidence supporting the likelihood of this association being causal, using data from previous work on the effects of surgical and pharmacological inhibition of gastric acid secretion on calcium absorption and bone mineral density. We will conclude by summarizing the current state of evidence on the relationship between gastric acid inhibition and the risk of fracture, and suggest management strategies for patients who require the long-term use of gastric acid inhibiting medications who also may be at risk for metabolic bone disease and fracture.

Maturitas. 2009 Sep 20;64(1):9-13

Adverse effects of proton pump inhibitors.

Proton pump inhibitors (PPI) are very effective drugs used largely in acid related disorders. During the last years concern have been raised regarding their overutilisation in benign condition, such as gastroesophageal reflux disease. The debate focussed also on the risk of adverse events related to long term use of PPI. Apart of the case of Helicobacter Pylori (H. Pylori) positive patients, in whose long term acid suppression lead to the development of corpus predominant atrophic gastritis, precursor of cancer; the other assumed adverse events, have never been demonstrated in prospective studies. The attention should move towards the appropriate prescription of PPI, rather than the fear adverse effects of PPI. In fact, in clinical practise, PPI are often prescribed in patients without a specific acid related disease and continued long term based on their safety profile. This review focus on the main adverse events related to long term PPI use.

Best Pract Res Clin Gastroenterol. 2010 Apr;24(2):193-201.

Long-term proton pump inhibitor therapy and risk of hip fracture.

CONTEXT: Proton pump inhibitors (PPIs) may interfere with calcium absorption through induction of hypochlorhydria but they also may reduce bone resorption through inhibition of osteoclastic vacuolar proton pumps. OBJECTIVE: To determine the association between PPI therapy and risk of hip fracture. DESIGN, SETTING, AND PATIENTS: A nested case-control study was conducted using the General Practice Research Database (1987-2003), which contains information on patients in the United Kingdom. The study cohort consisted of users of PPI therapy and nonusers of acid suppression drugs who were older than 50 years. Cases included all patients with an incident hip fracture. Controls were selected using incidence density sampling, matched for sex, index date, year of birth, and both calendar period and duration of up-to-standard follow-up before the index date. For comparison purposes, a similar nested case-control analysis for histamine 2 receptor antagonists was performed. MAIN OUTCOME MEASURE: The risk of hip fractures associated with PPI use. RESULTS: There were 13,556 hip fracture cases and 135,386 controls. The adjusted odds ratio (AOR) for hip fracture associated with more than 1 year of PPI therapy was 1.44 (95% confidence interval [CI], 1.30-1.59). The risk of hip fracture was significantly increased among patients prescribed long-term high-dose PPIs (AOR, 2.65; 95% CI, 1.80-3.90; P<.001). The strength of the association increased with increasing duration of PPI therapy (AOR for 1 year, 1.22 [95% CI, 1.15-1.30]; 2 years, 1.41 [95% CI, 1.28-1.56]; 3 years, 1.54 [95% CI, 1.37-1.73]; and 4 years, 1.59 [95% CI, 1.39-1.80]; P<.001 for all comparisons). CONCLUSION: Long-term PPI therapy, particularly at high doses, is associated with an increased risk of hip fracture.

JAMA. 2006 Dec 27;296(24):2947-53

Immune senscence

Effects of theabrownin from Pu-erh tea on the metabolism of serum lipids in rats: mechanism of action.

Theabrownin (TB), one of the main bioactive components in Pu-erh tea, has a significant blood lipid-lowering effect in hyperlipidemic rats. Therefore, it was hypothesized that TB would regulate the activity of key enzymes involved in lipid metabolism and accelerate the catabolism of exogenous cholesterol in rats fed a high fat diet. A total of 90 Sprague-Dawley rats were randomly divided into a normal control group (Group I), a high fat diet group (Group II), and high-fat diet plus TB group (Group III). A total of 10 rats were selected from each group and killed at 15, 30, or 45 d after starting the study for analysis. After feeding 45 d, the contents of TC, TG, and LDL-C levels in Group II were increased by 54.9%, 93.1%, and 134.3% compared with those in Group III, respectively, and the content of HDL-C in Group II was decreased by 55.7%. These effects were inhibited in the rats in Group III, which exhibited no significant differences in these levels compared with Group I, indicating that TB can prevent hyperlipidemia in rats fed a high fat diet. TB enhanced the activity of hepatic lipase and hormone-sensitive triglyceride lipase (HSL) and increased the HSL mRNA expression in liver tissue and epididymis tissue. The HL activity in serum of Group III was increased by 147.6% compared with that in Group II. The content of cholesterol and bile acid in the feces of rats was increased by 21.11- and 4.08-fold by TB. It suggested that TB could promote the transformation and excretion of dietary cholesterol of rats in vivo.

J Food Sci. 2010 Aug 1;75(6):H182-9

Effects of enzymatic action on the formation of theabrownin during solid state fermentation of Pu-erh tea.

BACKGROUND: Theabrownin (TB) is a main bioactive component in Pu-erh tea, and the total amount is between 100 and 140 g kg(-1). However, reports on the mechanism of formation of TB are sparse because it has a high molecular weight and complex composition. Hence, the mechanism of formation of TB in Pu-erh tea during solid state fermentation was investigated using an exogenous enzyme method. RESULTS: It was found that, in the presence of exogenous enzymes, the tea liquor prepared from the resulting leaves changed considerably in colour. In addition, the TB, total carbohydrate, polysaccharide, amino acid and protein contents were all increased, while the tea polyphenol content decreased sharply; the surfaces of leaves before fermentation appeared to be smooth and intact, and the structures of the cell, cellulose and lignin were complete, while after fermentation their surfaces were covered by microorganisms and the structures of the cells were largely disrupted. CONCLUSION: The enzymatic actions are closely related to the compositional changes occurring during Pu-erh tea manufacture, and its quality. Enzymes produced by microorganisms were found to be the main cause of TB formation during the fermentation of Pu-erh tea.

J Sci Food Agric. 2011 Oct;91(13):2412-8

Simultaneous determination of catechins, caffeine and gallic acids in green, Oolong, black and Pu-erh teas using HPLC with a photodiode array detector.

A simple and fast HPLC method using a photodiode array detector was developed for simultaneous determination of four major catechins, gallic acid and caffeine. After multiple extractions with aqueous methanol and acidic methanol solutions, tea extract was separated within 20 min using a methanol-acetate-water buffer gradient elution system on a C(18) column. The sample extraction data demonstrated that the single extraction used in the previous studies with aqueous acetonitrile or methanol is not sufficient; the multiple extraction procedure is essential for the quantitative analysis of catechins, phenolic acids and caffeine in teas. Several green, Oolong, black and Pu-erh teas were successfully analyzed by this method. The analytical results obtained indicated that green teas contain higher content of catechins [(-)-epigallocatechin gallate, (-)-epigallocatechin, (-)-epicatechin gallate, and (-)-epicatechin] than both Oolong, Pu-erh and black teas because fermentation process during the tea manufacturing reduced the levels of catechins significantly. The fermentation process also remarkably elevated the levels of gallic acid in full-fermented Pu-erh and black teas. Another interesting finding is the low level of caffeine in Oolong teas, especially in Fujian Oolong tea.

Talanta. 2002 May 16;57(2):307-16

Concise review: stem cell antigen-1: expression, function, and enigma.

Cloned 20 years ago, stem cell antigen-1 (Sca-1) is used extensively to enrich for murine hematopoietic stem cells. The realization that many different stem cell types share conserved biochemical pathways has led to a flood of recent research using Sca-1 as a candidate marker in the search for tissue-resident and cancer stem cells. Although surprisingly little is still known about its biochemical function, the generation and analysis of knockout mice has begun to shed light on the functions of Sca-1 in stem and progenitor cells, demonstrating that it is more than a convenient marker for stem cell biologists. This review summarizes the plethora of recent findings utilizing Sca-1 as a parenchymal stem cell marker and detailing its functional role in stem and progenitor cells and also attempts to explain the lingering mysteries surrounding its biochemical function and human ortholog. Disclosure of potential conflicts of interest is found at the end of this article.

Stem Cells. 2007 Jun;25(6):1339-47

Natural killer cell immunosenescence in acute myeloid leukaemia patients: new targets for immunotherapeutic strategies?

Several age-associated changes in natural killer (NK) cell phenotype have been reported that contribute to the defective NK cell response observed in elderly patients. A remodelling of the NK cell compartment occurs in the elderly with a reduction in the output of immature CD56bright cells and an accumulation of highly differentiated CD56dim NK cells. Acute myeloid leukaemia (AML) is generally a disease of older adults. NK cells in AML patients show diminished expression of several activating receptors that contribute to impaired NK cell function and, in consequence, to AML blast escape from NK cell immunosurveillance. In AML patients, phenotypic changes in NK cells have been correlated with disease progression and survival. NK cell-based immunotherapy has emerged as a possibility for the treatment of AML patients. The understanding of age-associated alterations in NK cells is therefore necessary to define adequate therapeutic strategies in older AML patients.

Cancer Immunol Immunother. 2015 Jun 10

The unmet need in the elderly: how immunosenescence, CMV infection, co-morbidities and frailty are a challenge for the development of more effective influenza vaccines.

Influenza remains the single most important cause of excess disability and mortality during the winter months. In spite of widespread influenza vaccination programs leading to demonstrated cost-savings in the over 65 population, hospitalization and death rates for acute respiratory illnesses continue to rise. As a person ages, increased serum levels of inflammatory cytokines are commonly recorded (TNF-a, IL-1, IL-6). Termed “inflammaging”, this has been linked to persistent cytomegalovirus (CMV) infection and immune senescence, while increased anti-inflammatory cytokines (IL-10, TGF-b) are possibly associated with more healthy aging. Paradoxically, a shift with aging toward an anti-inflammatory (IL-10) response and decline in the IFN-g:IL-10 ratio in influenza-challenged peripheral blood mononuclear cells is associated with a decline in the cytolytic capacity of CD8+ T cells responsible for clearing influenza virus from infected lung tissue. Thus, it is seemingly counter intuitive that the immune phenotype of healthy aging predicts a poor cell-mediated immune response and more serious outcomes of influenza. Herein we postulate a mechanistic link between the accumulation of late-stage, potentially terminally differentiated T cells, many or most of which result from CMV infection, and the immunopathogenesis of influenza infection, mediated by granzyme B in older adults. Further, adjuvanted influenza vaccines that stimulate inflammatory cytokines and suppress the IL-10 response to influenza challenge, would be expected to enhance protection in the 65+ population.

Vaccine. 2012 Mar 9;30(12):2060-7

Interleukin-6, C-reactive protein, and tumor necrosis factor-alpha as predictors of mortality in frail, community-living elderly individuals.

DESIGN: Prospective cohort study. SETTING: Data were from the Aging and Longevity Study in the Sirente Geographic Area, a prospective cohort study. PARTICIPANTS: Individuals aged 80 and older living in an Italian mountain community (N = 362). MEASUREMENTS: Participants were classified according to the median value of the three inflammation markers (IL-6, 2.08 pg/mL; TNF-a, 1.43 pg/mL; CRP, 3.08 mg/L). A composite summary score of inflammation was also created. The main outcome was risk of death after 4 years of follow-up. RESULTS: One hundred fifty deaths occurred during 4 years of follow-up. In the unadjusted model, high levels of each of the three markers were associated with greater mortality. After adjusting for potential confounders, high levels of IL-6 (hazard ratio (HR) = 2.18, 95% confidence interval (CI) = 1.29-3.69) and CRP (HR = 2.58, 95% CI = 1.52-4.40) were associated with a significantly greater risk of death, whereas the association between TNF-a protein levels and mortality was no longer significant (HR = 1.26, 95% CI = 0.74-2.15). The composite summary score of inflammation was strongly associated with mortality, with the highest risk estimated for individuals with all three inflammatory markers above the median. CONCLUSION: Low levels of inflammatory markers are associated with better survival in older adults, independent of age and other clinical and functional variables.

J Am Geriatr Soc. 2011 Sep;59(9):1679-85

Vitamin D

Effect of vitamin D supplementation on blood pressure: a systematic review and meta-analysis incorporating individual patient data.

IMPORTANCE: Low levels of vitamin D are associated with elevated blood pressure (BP) and future cardiovascular events. Whether vitamin D supplementation reduces BP and which patient characteristics predict a response remain unclear. OBJECTIVE: To systematically review whether supplementation with vitamin D or its analogues reduce BP. DATA SOURCES: We searched MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and augmented by a hand search of references from the included articles and previous reviews. Google was searched for gray literature (ie, material not published in recognized scientific journals). No language restrictions were applied. The search period spanned January 1, 1966, through March 31, 2014. STUDY SELECTION: We included randomized placebo-controlled clinical trials that used vitamin D supplementation for a minimum of 4 weeks for any indication and reported BP data. Studies were included if they used active or inactive forms of vitamin D or vitamin D analogues. Cointerventions were permitted if identical in all treatment arms. DATA EXTRACTION AND SYNTHESIS: We extracted data on baseline demographics, 25-hydroxyvitamin D levels, systolic and diastolic BP (SBP and DBP), and change in BP from baseline to the final follow-up. Individual patient data on age, sex, medication use, diabetes mellitus, baseline and follow-up BP, and 25-hydroxyvitamin D levels were requested from the authors of the included studies. For trial-level data, between-group differences in BP change were combined in a random-effects model. For individual patient data, between-group differences in BP at the final follow up, adjusted for baseline BP, were calculated before combining in a random-effects model. MAIN OUTCOMES AND MEASURES: Difference in SBP and DBP measured in an office setting. RESULTS: We included 46 trials (4541 participants) in the trial-level meta-analysis. Individual patient data were obtained for 27 trials (3092 participants). At the trial level, no effect of vitamin D supplementation was seen on SBP (effect size, 0.0 [95% CI, -0.8 to 0.8] mm Hg; P=.97; I2=21%) or DBP (effect size, -0.1 [95% CI, -0.6 to 0.5] mm Hg; P=.84; I2=20%). Similar results were found analyzing individual patient data for SBP (effect size, -0.5 [95% CI, -1.3 to 0.4] mm Hg; P=.27; I2=0%) and DBP (effect size, 0.2 [95% CI, -0.3 to 0.7] mm Hg; P=.38; I2=0%). Subgroup analysis did not reveal any baseline factor predictive of a better response to therapy. CONCLUSIONS AND RELEVANCE: Vitamin D supplementation is ineffective as an agent for lowering BP and thus should not be used as an antihypertensive agent.

JAMA Intern Med. 2015 May;175(5):745-54

Vitamin D: important for prevention of osteoporosis, cardiovascular heart disease, type 1 diabetes, autoimmune diseases, and some cancers.

Vitamin D is very important for overall health and wellbeing. A major source of vitamin D comes from exposure to sunlight. Measurement of 25-hydroxyvitamin D in the blood and not 1,25-dihydroxyvitamin D is used to determine vitamin D status. A blood level of 25-hydroxyvitamin D of at least 20 ng/mL is considered to be vitamin D sufficient. Vitamin D deficiency increases the risk of many common cancers, multiple sclerosis, rheumatoid arthritis, hypertension, cardiovascular heart disease, and type I diabetes.

South Med J. 2005 Oct;98(10):1024-7

Effects of six months of vitamin D supplementation in patients with heart failure: a randomized double-blind controlled trial.

BACKGROUND AND AIM: Low plasma vitamin D levels have been associated with heart failure (HF). This research attempts to explain the role of vitamin D supplementation on myocardial function in elderly patients with HF. METHODS AND RESULTS: Twenty-three chronic HF patients were randomized in a small parallel group, double-blind, placebo-controlled trial. All patients, with a mean age of 74 years and vitamin D levels <30 ng/mL, received 800,000 IU (4000 IU/daily) of cholecalciferol or placebo for 6 months. The outcomes measured at baseline and after 6 months were ejection fraction (EF) and other echocardiography parameters, carboxyterminal propeptide of procollagen type I (PIP), natriuretic peptides, lipid profile, renin, parathyroid hormone, blood pressure, and body mass index (BMI). In 13 patients under active treatment for 6 months, mean plasma 25-hydroxy vitamin D concentrations (15.51 vs. -1.40 ng/mL, p < 0.001) and plasma calcium (from 9.3 to 9.6 mmol/L, p < 0.05) increased significantly. However, other biomarkers of bone metabolism did not differ between the treatment and placebo groups. EF increased significantly in the intervention group (6.71 vs. -4.3%; p < 0.001), and the serum concentration of PIP increased only in the placebo group after 6 months (1140.98 vs. -145 mcg/L; p < 0.05). Systolic blood pressure was lower after 6 months of cholecalciferol treatment (from 129.6 to 122.7 mm Hg, p < 0.05). No significant variations were observed for other parameters. CONCLUSIONS: Six months of vitamin D supplementation significantly improves EF in elderly patients with HF and vitamin D deficiency.

Nutr Metab Cardiovasc Dis. 2014 Aug;24(8):861-8

Relationship between 25-hydroxyvitamin D and all-cause and cardiovascular disease mortality.

BACKGROUND: Observational studies have suggested a strong relationship between 25(OH)D and all-cause and cardiovascular disease mortality. A few studies also have described a nonlinear trend for this relationship in population subgroups, but less is known about this relationship in healthy adults. We examined the presence of a nonlinear relationship between 25(OH)D and all-cause and cardiovascular disease mortality among healthy adults. METHODS: We examined 10,170 participants (≥18 years of age) using National Health and Nutrition Examination Survey data (2001-2004) combined with National Death Index for vital status information through December 2006. Cox proportional hazard models with spline (single knot at population median of 25[OH]D) were fit to estimate hazard ratios (HRs) for all-cause and cardiovascular disease mortality for each 10-unit increase in serum 25(OH)D. Models were adjusted for demographic and conventional cardiovascular disease risk factors. RESULTS: Mean age of study participants was 46.6 (20.5) years, while median (interquartile range) 25(OH)D was 21 (15-27) ng/mL. After a median follow-up of 3.8 years (range 2.8-4.9), 509 all-cause and 184 cardiovascular diseases-related deaths were observed. In univariate analysis, 25(OH)D decreased hazards of all-cause (HR 0.59; 95% confidence interval [CI], 0.45-0.77) and cardiovascular disease (HR 0.56; 95% CI, 0.38-0.82) mortality below but not above its population median. In adjusted models, 25(OH)D retained the inverse association for all-cause (HR 0.54; 95% CI, 0.35-0.84) and cardiovascular disease (HR 0.50; 95% CI, 0.26-0.98) mortality below but not above its population median. CONCLUSIONS: We found an inverse association between 25(OH)D and all-cause and cardiovascular disease mortality in healthy adults with serum 25(OH)D levels of ≤21 ng/mL. Clinical trials for the primary prevention of cardiovascular disease with 25(OH)D supplementation may target healthy adults with serum 25(OH)D levels of ≤21 ng/mL to validate these findings.

Am J Med. 2013 Jun;126(6):509-14

Impact of vitamin D supplementation on arterial vasomotion, stiffness and endothelial biomarkers in chronic kidney disease patients.

BACKGROUND: Cardiovascular events are frequent and vascular endothelial function is abnormal in patients with chronic kidney disease (CKD). We demonstrated endothelial dysfunction with
vitamin D deficiency in CKD patients; however the impact of cholecalciferol supplementation on vascular stiffness and vasomotor function, endothelial and bone biomarkers in CKD patients with low 25-hydroxy vitamin D [25(OH)D] is unknown, which this study investigated. METHODS: We assessed non-diabetic patients with CKD stage 3/4, age 17-80 years and serum 25(OH)D <75 nmol/L. Brachial artery Flow Mediated Dilation (FMD), Pulse Wave Velocity (PWV), Augmentation Index (AI) and circulating blood biomarkers were evaluated at baseline and at 16 weeks. Oral 300,000 units cholecalciferol was administered at baseline and 8-weeks. RESULTS: Clinical characteristics of 26 patients were: age 50±14 (mean±1SD) years, eGFR 41±11 ml/min/1.73 m2, males 73%, dyslipidaemia 36%, smokers 23% and hypertensives 87%. At 16-week serum 25(OH)D and calcium increased (43±16 to 84±29 nmol/L, p<0.001 and 2.37±0.09 to 2.42±0.09 mmol/L; p = 0.004, respectively) and parathyroid hormone decreased (10.8±8.6 to 7.4±4.4; p = 0.001). FMD improved from 3.1±3.3% to 6.1±3.7%, p = 0.001. Endothelial biomarker concentrations decreased: E-Selectin from 5666±2123 to 5256±2058 pg/mL; p = 0.032, ICAM-1, 3.45±0.01 to 3.10±1.04 ng/mL; p = 0.038 and VCAM-1, 54±33 to 42±33 ng/mL; p = 0.006. eGFR, BP, PWV, AI, hsCRP, von Willebrand factor and Fibroblast Growth Factor-23, remained unchanged. CONCLUSION: This study demonstrates for the first time improvement of endothelial vasomotor and secretory functions with vitamin D in CKD patients without significant adverse effects on arterial stiffness, serum calcium or FGF-23. TRIAL

PLoS One. 2014 Mar 19;9(3):e91363

Vitamin D3 supplementation for 16 weeks improves flow-mediated dilation in overweight African-American adults.

BACKGROUND: A growing body of evidence has linked vitamin D deficiency to increased risk of cardiovascular disease. Vitamin D deficiency is also more common in African Americans for whom an increased cardiovascular disease risk exists. This study sought to test the hypothesis that 16 weeks of 60,000 IU monthly supplementation of oral vitamin D(3) would improve flow-mediated dilation (FMD) in African Americans, whereas no change would be observed in the placebo group. METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted. Fifty-seven African-American adults were randomly assigned to either the placebo group or vitamin D group. RESULTS: Following 16 weeks of placebo (n = 23; mean age 31 ± 2 years) or 60,000 IU monthly oral vitamin D(3) (n = 22; mean age 29 ± 2 years), serum concentrations of 25-hydroxyvitamin D (25(OH)D) increased from 38.2 ± 3.0 to 48.7 ± 3.2 nmol/l and 34.3 ± 2.2 to 100.9 ± 6.6 nmol/l, respectively. No changes in serum parathyroid hormone (PTH), serum calcium, or urine calcium/creatinine were observed following either treatment. Following 16 weeks of treatment, significant improvements in FMD were only observed in the vitamin D group (1.8 ± 1.3%), whereas the placebo group had no change (-1.3 ± 0.6%). Similarly, the vitamin D group exhibited an increase in absolute change in diameter (0.005 ± 0.004 cm) and FMD/shear (0.08 ± 0.04 %/s(-1), area under the curve (AUC) × 10(3)) following treatment, whereas no change (-0.005 ± 0.002 cm and -0.02 ± 0.02 %/s(-1), AUC, respectively) was observed following placebo. CONCLUSION: Supplementation of 60,000 IU monthly oral vitamin D(3) (~2,000 IU/day) for 16 weeks is effective at improving vascular endothelial function in African-American adults.

Am J Hypertens. 2011 May;24(5):557-62.