The promise of dietary restriction mimetics in healthy aging

Posted on July 4, 2013 by Maurice Preter MD
Biofactors. 2010 Sep-Oct;36(5):377-82. doi: 10.1002/biof.127.

Life span extension by resveratrol, rapamycin, and metformin: The promise of dietary restriction mimetics for an healthy aging.

Source

UMR, CNRS Université Lyon, Centre Léon Bérard, France.

Abstract

Life expectancy at the turn of the 20th century was 46 years on average worldwide and it is around 65 years today. The correlative increase in age-associated diseases incidence has a profound public health impact and is an important matter of concern for our societies. Aging is a complex, heterogeneous, and multifactorial phenomenon, which is the consequence of multiple interactions between genes and environment. In this review, we survey animals models that have been of great help for both investigating mechanism of aging and identifying molecules, which slow down the onset of age-related diseases. Resveratrol (RSV) is one of those. We will report evidences supporting RSV as a molecule that acts by mimicking the beneficial effects of dietary restriction, and may share common downstream targets with rapamycin and metformin. Although those molecules do not reveal all the secrets of the fountain of youth, they may help us maintaining the quality of life in the old age.

© 2010 International Union of Biochemistry and Molecular Biology, Inc.

PMID:
20848587
[PubMed – indexed for MEDLINE]
Posted in Aging, China, Complementary - Alternative Medicine, epigenetics, Fifth Avenue Concierge Medicine, Forensic Neuropsychiatry, Health, keto, metabolic, new treatments, News, Psychiatry/Neurology | Tagged , , , , |

Traumatic brain injury may be an independent risk factor for stroke

Posted on July 1, 2013 by Maurice Preter MD

Traumatic brain injury may be an independent risk factor for stroke

  1. James F. Burke, MD, MS,
  2. Jessica L. Stulc, MD, MPH,
  3. Lesli E. Skolarus, MD, MS,
  4. Erika D. Sears, MD, MS,
  5. Darin B. Zahuranec, MD, MS and
  6. Lewis B. Morgenstern, MD

+Show Affiliations

| + Show Full Disclosures

  1. Correspondence to Dr. Burke: jamesbur@umich.edu
  1. Published online before print June 26, 2013, doi: 10.1212/WNL.0b013e318297eecf Neurology July 2, 2013 vol. 81 no. 1 33-39
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Abstract

Objective: To explore whether traumatic brain injury (TBI) may be a risk factor for subsequent ischemic stroke.

Methods: Patients with any emergency department visit or hospitalization for TBI (exposed group) or non-TBI trauma (control) based on statewide emergency department and inpatient databases in California from 2005 to 2009 were included in a retrospective cohort. TBI was defined using the Centers for Disease Control definition. Our primary outcome was subsequent hospitalization for acute ischemic stroke. The association between TBI and stroke was estimated using Cox proportional hazards modeling adjusting for demographics, vascular risk factors, comorbidities, trauma severity, and trauma mechanism.

Results: The cohort included a total of 1,173,353 trauma subjects, 436,630 (37%) with TBI. The patients with TBI were slightly younger than the controls (mean age 49.2 vs 50.3 years), less likely to be female (46.8% vs 49.3%), and had a higher mean injury severity score (4.6 vs 4.1). Subsequent stroke was identified in 1.1% of the TBI group and 0.9% of the control group over a median follow-up period of 28 months (interquartile range 14–44). After adjustment, TBI was independently associated with subsequent ischemic stroke (hazard ratio 1.31, 95% confidence interval 1.25–1.36).

Conclusions: In this large cohort, TBI is associated with ischemic stroke, independent of other major predictors.

Footnotes

via Traumatic brain injury may be an independent risk factor for stroke.

Posted in Aging, China, Fifth Avenue Concierge Medicine, Forensic Neuropsychiatry, Health, keto, News, Psychiatry/Neurology | Tagged , , |

Vitamin D and risk of death from vascular and no… [Eur Heart J. 2013] – PubMed – NCBI

Posted on June 25, 2013 by Maurice Preter MD
Eur Heart J. 2013 May;34(18):1365-74. doi: 10.1093/eurheartj/ehs426. Epub 2012 Dec 20.

Vitamin D and risk of death from vascular and non-vascular causes in the Whitehall study and meta-analyses of 12,000 deaths.

Tomson J, Emberson J, Hill M, Gordon A, Armitage J, Shipley M, Collins R, Clarke R.

Source

Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK.

Abstract

AIMS:

To examine the independent relevance of plasma concentrations of 25-hydroxyvitamin D [25(OH)D] for vascular and non-vascular mortality.

METHODS AND RESULTS:

We examined associations of plasma concentrations of 25(OH)D and cause-specific mortality in a prospective study of older men living in the UK and included findings in meta-analyses of similar studies identified by a systematic search reporting on vascular and all-cause mortality. In a 13-year follow-up of 5409 men (mean baseline age 77 years), 1358 died from vascular and 1857 from non-vascular causes. Median season-adjusted baseline 25(OH)D concentration was 56 (interquartile range: 45-67) nmol/L. After adjustment for age and seasonality, higher concentrations of 25(OH)D were inversely and approximately linearly (log-log scale) associated with vascular and non-vascular mortality throughout the range 40-90 nmol/L. After additional adjustment for prior disease and cardiovascular risk factors, a doubling in 25(OH)D concentration was associated with 20% [95% confidence interval (CI): 9-30%] lower vascular and 23% (95% CI: 14-31%) lower non-vascular mortality. In meta-analyses of prospective studies, individuals in the top vs. bottom quarter of 25(OH)D concentrations had 21% (95% CI: 13-28%) lower vascular and 28% (95% CI: 24-32%) lower all-cause mortality.

CONCLUSIONS:

Despite strong inverse and apparently independent associations of 25(OH)D with vascular and non-vascular mortality, causality remains uncertain. Large-scale randomized trials, using high doses of vitamin D, are required to assess the clinical relevance of these associations.

KEYWORDS:

Cardiovascular disease, Mortality, Vitamin D

via Vitamin D and risk of death from vascular and no… [Eur Heart J. 2013] – PubMed – NCBI.

Posted in Aging, dietary, epigenetics, Events, Fifth Avenue Concierge Medicine, Forensic Neuropsychiatry, Health, keto, new treatments, News, Psychiatry/Neurology | Tagged , , , |

Epidemiology of Alzheimer’s disease and other forms of dementia in China, 1990–2010: a systematic review and analysis : The Lancet

Posted on June 19, 2013 by Maurice Preter MD

“Our analysis suggests that previous estimates of dementia burden, based on smaller datasets, might have underestimated the burden of dementia in China.”

Epidemiology of Alzheimer’s disease and other forms of dementia in China, 1990—2010: a systematic review and analysis

Kit Yee Chan PhD a d, Wei Wang MPH b, Jing Jing Wu MPH b, Li Liu PhD c, Evropi Theodoratou PhD d, Josip Car PhD g, Prof Lefkos Middleton MD g, Tom C Russ MTCPsych e f h, Prof Ian J Deary FRSE e f, Prof Harry Campbell MD d †, Prof Wei Wang PhD b i Corresponding Author †Email Address, Prof Igor Rudan PhD d Corresponding Author †Email Address, on behalf of the Global Health Epidemiology Reference Group (GHERG)

Summary

Background

China is increasingly facing the challenge of control of the growing burden of non-communicable diseases. We assessed the epidemiology of Alzheimer’s disease and other forms of dementia in China between 1990, and 2010, to improve estimates of the burden of disease, analyse time trends, and inform health policy decisions relevant to China’s rapidly ageing population.

Methods

In our systematic review we searched for reports of Alzheimer’s disease or dementia in China, published in Chinese and English between 1990 and 2010. We searched China National Knowledge Infrastructure, Wanfang, and PubMed databases. Two investigators independently assessed case definitions of Alzheimer’s disease and dementia: we excluded studies that did not use internationally accepted case definitions. We also excluded reviews and viewpoints, studies with no numerical estimates, and studies not done in mainland China. We used Poisson regression and UN demographic data to estimate the prevalence (in nine age groups), incidence, and standardised mortality ratio of dementia and its subtypes in China in 1990, 2000, and 2010.

Findings

Our search returned 12 642 reports, of which 89 met the inclusion criteria (75 assessed prevalence, 13 incidence, and nine mortality). In total, the included studies had 340 247 participants, in which 6357 cases of Alzheimer’s disease were recorded. 254 367 people were assessed for other forms of dementia, of whom 3543 had vascular dementia, frontotemporal dementia, or Lewy body dementia. In 1990 the prevalence of all forms of dementia was 1·8% (95% CI 0·0—44·4) at 65—69 years, and 42·1% (0·0—88·9) at age 95—99 years. In 2010 prevalence was 2·6% (0·0—28·2) at age 65—69 years and 60·5% (39·7—81·3) at age 95—99 years. The number of people with dementia in China was 3·68 million (95% CI 2·22—5·14) in 1990, 5·62 million (4·42—6·82) in 2000, and 9·19 million (5·92—12·48) in 2010. In the same period, the number of people with Alzheimer’s disease was 1·93 million (1·15—2·71) in 1990, 3·71 million (2·84—4·58) people in 2000, and 5·69 million (3·85—7·53) in 2010. The incidence of dementia was 9·87 cases per 1000 person-years, that of Alzheimer’s disease was 6·25 cases per 1000 person-years, that of vascular dementia was 2·42 cases per 1000 person-years, and that of other rare forms of dementia was 0·46 cases per 1000 person-years. We retrieved mortality data for 1032 people with dementia and 20 157 healthy controls, who were followed up for 3—7 years. The median standardised mortality ratio was 1·94:1 (IQR 1·74—2·45).

Interpretation

Our analysis suggests that previous estimates of dementia burden, based on smaller datasets, might have underestimated the burden of dementia in China. The burden of dementia seems to be increasing faster than is generally assumed by the international health community. Rapid and effective government responses are needed to tackle dementia in low-income and middle-income countries.

Funding

Nossal Institute of Global Health (University of Melbourne, Australia), the National 12th Five-Year Major Projects of China, National Health and Medical Research Council Australia—China Exchange Fellowship, Importation and Development of High-Calibre Talents Project of Beijing Municipal Institutions, and the Bill & Melinda Gates Foundation.

via Epidemiology of Alzheimer’s disease and other forms of dementia in China, 1990–2010: a systematic review and analysis : The Lancet.

Posted in Aging, China, dietary, Events, Fifth Avenue Concierge Medicine, Health, keto, News, Psychiatry/Neurology | Tagged , , |

More on Vitamin D deficiency in Hashimoto’s thyroiditis

Posted on June 19, 2013 by Maurice Preter MD

The need for high dose steroid treatment or even IVIG seems to be called into question based on these results. One ounce of prevention?

1.    J Pediatr Endocrinol Metab. 2012;25(5-6):467-70.
Vitamin D status in children with Hashimoto thyroiditis.

Camurdan OM, Döğer E, Bideci A, Celik N, Cinaz P.
Department of Pediatric Endocrinology, School of Medicine, Gazi University, Ankara, Turkey. turkalpo@yahoo.com
Abstract

OBJECTIVE:

To investigate vitamin D status in children with Hashimoto thyroiditis.

SUBJECTS AND METHODS:

The study group consisted of 78 children recently diagnosed as Hashimoto thyroiditis and 74 subjects as the control group. Parameters of calcium metabolism, thyroid function tests, and 25-hydroxyvitamin D [25(OH)D] levels were measured.

RESULTS:

Vitamin D deficiency rate was significantly higher in the Hashimoto group compared with the control subjects (73.1% vs. 17.6%, p < 0.0001). In the Hashimoto group, mean 25(OH)D levels were significantly lower compared with the control group (31.2 +/- 11.5 versus 57.9 +/- 19.7 nmol/L, p < 0.001) and was inversely correlated with the anti-thyroid peroxidase (anti-TPO) levels (r = -0.30, p = 0.007).

CONCLUSION:

The higher vitamin D deficiency rates besides lower vitamin D levels in the Hashimoto group together with the inverse correlation between vitamin D and anti-TPO suggest that vitamin D deficiency may have a role in the autoimmune process in Hashimoto thyroiditis in children.

PMID: 22876540 [PubMed – indexed for MEDLINE]
Related citations
2.    Thyroid. 2011 Aug;21(8):891-6. doi: 10.1089/thy.2009.0200. Epub 2011 Jul 13.
Relative vitamin D insufficiency in Hashimoto’s thyroiditis.

Tamer G, Arik S, Tamer I, Coksert D.
Department of Endocrinology and Metabolism, Goztepe Education and Research Hospital, Istanbul, Turkey. hgtamer@yahoo.com
Abstract

BACKGROUND:

Vitamin D insufficiency, defined as serum levels of 25-hydroxyvitamin D [25(OH)D3] lower than 30 ng/mL, has been reported to be prevalent in several autoimmune diseases such as multiple sclerosis and type 1 diabetes mellitus. The goal of the present study was to assess whether vitamin D insufficiency is also a feature of Hashimoto’s thyroiditis (HT).

METHODS:

We performed a prevalence case-control study that included 161 cases with HT and 162 healthy controls. Serum levels of 25(OH)D3, calcium, phosphorus, and parathyroid hormone were measured in all 323 subjects.

RESULTS:

The prevalence of vitamin D insufficiency in HT cases (148 of 161, 92%) was significantly higher than that observed in healthy controls (102 of 162, 63%, p < 0.0001). Among HT cases, the prevalence rate of vitamin D insufficiency showed a trend to be higher in patients with overt hypothyroidism (47 of 50, 94%) or subclinical hypothyroidism (44 of 45, 98%) than in those with euthyroidism (57 of 66, 86%), but the differences were not significant (p = 0.083).

CONCLUSION:

Vitamin D insufficiency is associated with HT. Further studies are needed to determine whether vitamin D insufficiency is a casual factor in the pathogenesis of HT or rather a consequence of the disease.

PMID: 21751884 [PubMed – indexed for MEDLINE]
Related citations

3.    Diabetologia. 2009 Dec;52(12):2542-50. doi: 10.1007/s00125-009-1554-x. Epub 2009 Oct 13.
Calcium, vitamin D and dairy intake in relation to type 2 diabetes risk in a Japanese cohort.

Kirii K, Mizoue T, Iso H, Takahashi Y, Kato M, Inoue M, Noda M, Tsugane S; Japan Public Health Center-based Prospective Study Group.
Collaborators: Tsugane S, Inoue M, Sobue T, Hanaoka T, Ogata J, Baba S, Mannami T, Okayama A, Kokubo Y, Miyakawa K, Saito F, Koizumi A, Sano Y, Hashimoto I, Ikuta T, Tanaba Y, Miyajima Y, Suzuki N, Nagasawa S, Furusugi Y, Nagai N, Sanada H, Hatayama Y, Kobayashi F, Uchino H, Shirai Y, Kondo T, Sasaki R, Watanabe Y, Miyagawa Y, Kobayashi Y, Kishimoto Y, Takara E, Fukuyama T, Kinjo M, Irei M, Sakiyama H, Imoto K, Yazawa H, Seo T, Seiko A, Ito F, Shoji F, Saito R, Murata A, Minato K, Motegi K, Fujieda T, Matsui K, Abe T, Katagiri M, Suzuki M, Doi M, Terao A, Ishikawa Y, Tagami T, Sueta H, Doi M, Urata M, Okamoto N, Ide F, Sakiyama H, Onga N, Takaesu H, Uehara M, Horii F, Asano I, Yamaguchi H, Aoki K, Maruyama S, Ichii M, Takano M, Tsubono Y, Suzuki K, Honda Y, Yamagishi K, Sakurai S, Tsuchiya N, Kabuto M, Yamaguchi M, Matsumura Y, Sasaki S, Watanabe S, Akabane M, Kadowaki T, Noda M, Mizoue T, Kawaguchi Y, Takashima Y, Yoshida M, Nakamura K, Matsushima S, Natsukawa S, Shimizu H, Sugimura H, Tominaga S, Iso H, Iida M, Ajiki W, Ioka A, Sato S, Maruyama E, Konishi M, Okada K, Saito I, Yasuda N, Kono S.

Department of Epidemiology and International Health, Research Institute, International Medical Center of Japan, Tokyo, Japan.

Abstract

AIMS/HYPOTHESIS:

Calcium and vitamin D have been implicated in the development of type 2 diabetes, but epidemiological evidence is limited. We examined prospectively the relation of calcium and vitamin D intake to type 2 diabetes risk in a Japanese cohort.

METHODS:

Participants were 59,796 middle-aged and older men and women, who participated in the Japan Public Health Center-based Prospective Study and had no history of type 2 diabetes or other serious diseases. Dietary intake of calcium and vitamin D were estimated using a validated food frequency questionnaire. Logistic regression was used to assess the association between intake of these nutrients and self-reported newly diagnosed type 2 diabetes.

RESULTS:

During a 5 year follow-up, 1,114 cases of type 2 diabetes were documented. Overall, calcium intake was not associated with a significantly lower risk of type 2 diabetes; the multivariable odds ratio for the highest vs lowest quartiles was 0.93 (95% CI 0.71-1.22) in men and 0.76 (95% CI 0.56-1.03) in women. However, among participants with a higher vitamin D intake, calcium intake was inversely associated with diabetes risk; the odds ratio for the highest vs lowest intake categories was 0.62 (95% CI 0.41-0.94) in men and 0.59 (95% CI 0.38-0.91) in women. Dairy food intake was significantly associated with a lower risk of type 2 diabetes in women only.

CONCLUSIONS/INTERPRETATION:

Calcium and vitamin D may not be independently associated with type 2 diabetes risk. Our finding suggesting a joint action of these nutrients against type 2 diabetes warrants further investigation.

PMID: 19823801 [PubMed – indexed for MEDLINE]
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4.    Int J Immunogenet. 2008 Apr;35(2):125-31. doi: 10.1111/j.1744-313X.2008.00748.x. Epub 2008 Feb 11.
Association of vitamin D receptor gene 3′-variants with Hashimoto’s thyroiditis in the Croatian population.

Stefanić M, Papić S, Suver M, Glavas-Obrovac L, Karner I.
Department of Nuclear Medicine, Radiation Protection and Pathophysiology, Clinical Hospital Osijek, Osijek, Croatia.

Abstract

Hashimoto’s thyroiditis (HT) is the most frequent autoimmune thyroid disease with strong genetic background. Vitamin D receptor (VDR) endocrine system affects immunosuppressive, regulatory and tolerogenic decisions required for induction and maintenance of peripheral immune tolerance. With respect to the biological function of the VDR and functionally plausible gene-expression data, we sought to test whether particular 3′-restriction fragment length polymorphisms (RFLP) and haplotypes previously directly or indirectly associated with VDR mRNA 3′-allelic imbalance phenotype and differences in total VDR mRNA expression are implicated in HT susceptibility. Thus, 145 Croatian HT patients and 145 age-, sex- and ethnically matched euthyroid controls were genotyped for VDR rs1544410 (BsmI), rs7975232 (ApaI) and rs731236 (TaqI) polymorphisms by polymerase chain reaction-RFLP method. Covariate-adjusted single-locus and haplotype-phenotype regression analyses were performed. Permutation corrections (P(c)) and Akaike Information Criteria were used for model comparisons. The best-fit [global P(c) = 7.2 x 10(-4)]BsmI-TaqI BT haplotype was found significantly more often in subjects without HT [12.2% vs. 3.7%; odds ratio (OR, 95% confidence intervals) = 0.28 (0.14-0.56), P(c) = 8 x 10(-4)], whereas the bT haplotype was significantly more frequent in individuals with HT [45.7% vs. 61.8%; OR = 1.91 (1.37-2.65), P(c) = 4 x 10(-4)]. Two extended BsmI-ApaI-TaqI RFLP haplotypes, the common baT [35.7 vs. 47.3%, OR = 1.63 (1.17-2.27), P(c) = 0.012] and rare BaT variants [6.5 vs. 1.2%, OR = 0.17 (0.06-0.55), P(c) = 1.2 x 10(-3)] were associated with HT, representing predisposing and protective haplotypes, respectively. In single-RFLP association analyses, only rs1544410 polymorphism was associated with HT phenotype (allelic P(c) = 0.0078) and appeared to function under the recessive model, with decreased risk of HT among the BB homozygotes [OR = 0.39 (0.21-0.7), P(c) = 0.0052] when compared to the reference b(+)-genotypes. These data suggest that common haplotypic variants within the VDR gene 3′-region previously linked to VDR mRNA expression and allelic imbalance could be associated with HT in the general population, and thus, may be involved in the pathogenesis of HT.

PMID: 18279374 [PubMed – indexed for MEDLINE]
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5.    J Clin Lab Anal. 2006;20(3):109-12.
Vitamin D receptor gene polymorphisms are associated with risk of Hashimoto’s thyroiditis in Chinese patients in Taiwan.

Lin WY, Wan L, Tsai CH, Chen RH, Lee CC, Tsai FJ.
Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan.

Abstract

The etiology of the autoimmune thyroid, Hashimoto’s thyroiditis (HT) is not very clear. However, genetic susceptibility is thought to play a critical role. The vitamin D receptor (VDR)-related endocrine system has been demonstrated to be able to carry out modulation of the immune response. Here, we investigated whether single nucleotide polymorphisms (SNPs) of VDR are associated with HT patients. VDR SNP was detected by polymerase chain reaction (PCR)-based restriction analysis in 109 patients with HT and 90 normal controls. Significant differences were found in the genotype distribution of VDR SNP between Hashimoto’s thyroiditis patients and controls (P=0.0458). Allelic frequency of the VDR gene distinguished HT patients from controls (P=0.0089). The results revealed a significant difference between HT patients and normal controls in VDR SNP and a statistic correlation between VDR-FokI polymorphisms and HT formation. It could be concluded that patients who carry the C/C homozygote of the VDR-FokI gene polymorphism in exon 2 may have a higher risk of developing HT in Chinese patients in Taiwan.

(c) 2006 Wiley-Liss, Inc.

PMID: 16721822 [PubMed – indexed for MEDLINE]
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