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Brett Black

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  1. Very high doses of a vitamin are deleterious to health - and water is wet :)... but seriously, yes, this is important. Some here might take at least B12 since a vegan might have problems getting it from diet. Presumably not super high doses, but it's a cautionary note.

    In my experience it's uncommon to find B12 tablets less than 100µg, which is over 40 times the RDI and almost twice the dose shown in this study to be linked to a doubling of lung cancer risk. My impression is that 1000µg B12 tablets may actually be the most commonly available dose - over 400 times the RDI. So it wouldn't surprise me to find people taking such doses.

  2. 1. J Clin Oncol. 2017 Oct 20;35(30):3440-3448. doi: 10.1200/JCO.2017.72.7735. Epub

    2017 Aug 22.


    Long-Term, Supplemental, One-Carbon Metabolism-Related Vitamin B Use in Relation

    to Lung Cancer Risk in the Vitamins and Lifestyle (VITAL) Cohort.


    Brasky TM(1), White E(1), Chen CL(1).


    Author information:

    (1)Theodore M. Brasky, The Ohio State University College of Medicine, Columbus,

    OH; Theodore M. Brasky and Emily White, Fred Hutchinson Cancer Research Center,

    Seattle, WA; Chi-Ling Chen, College of Public Health and College of Medicine,

    National Taiwan University, Taipei, Taiwan.


    Purpose Inconsistent findings have been reported of a link between the use of

    one-carbon metabolism-related B vitamins and lung cancer risk. Because of the

    high prevalence of supplemental vitamin B use, any possible increased association

    warrants further investigation. We examined the association between long-term use

    of supplemental B vitamins on the one-carbon metabolism pathway and lung cancer

    risk in the Vitamins and Lifestyle (VITAL) cohort, which was designed

    specifically to look at supplement use relative to cancer risk.


    Methods A total

    of 77,118 participants of the VITAL cohort, 50 to 76 years of age, were recruited

    between October 2000 and December 2002 and included in this analysis. Incident,

    primary, invasive lung cancers (n = 808) were ascertained by prospectively

    linking the participants to a population-based cancer registry. The 10-year

    average daily dose from individual and multivitamin supplements were the

    exposures of primary interest.


    Results Use of supplemental vitamins B6, folate,

    and B12 was not associated with lung cancer risk among women. In contrast, use of

    vitamin B6 and B12 from individual supplement sources, but not from

    multivitamins, was associated with a 30% to 40% increase in lung cancer risk

    among men. When the 10-year average supplement dose was evaluated, there was an

    almost two-fold increase in lung cancer risk among men in the highest categories

    of vitamin B6 (> 20 mg/d; hazard ratio, 1.82; 95% CI, 1.25 to 2.65) and B12 (>

    55µg/d; hazard ratio, 1.98; 95% CI, 1.32 to 2.97) compared with nonusers. For

    vitamin B6 and B12, the risk was even higher among men who were smoking at

    baseline. In addition, the B6 and B12 associations were apparent in all

    histologic types except adenocarcinoma, which is the type less related to



    Conclusion This sex- and source-specific association provides further

    evidence that vitamin B supplements are not chemopreventive for lung cancer and

    may be harmful.


    DOI: 10.1200/JCO.2017.72.7735

    PMID: 28829668








    Some media articles interviewing an author of the new study and also referencing previous studies showing links between B12 and B6 supplementation and cancer:



  3. “Once upon a time, I dreamt I was a butterfly, fluttering hither and thither, to all intents and purposes a butterfly. I was conscious only of my happiness as a butterfly, unaware that I was myself. Soon I awaked, and there I was, veritably myself again. Now I do not know whether I was then a man dreaming I was a butterfly, or whether I am now a butterfly, dreaming I am a man.” - Zhuangzhi c. third century BC

  4. WHO guidelines on hours of exercise needed to stay healthy are way off, Queensland study finds

    By Allyson Horn


    People need to do five times the exercise recommended by the World Health Organisation (WHO) to stay healthy, a Queensland study has found.

    Researchers from the University of Queensland studied the link between physical activity and chronic health conditions including breast and bowel cancer, diabetes, heart disease and stroke.

    They found exercise levels recommended by the WHO needed to be much higher to increase resistance.


    Researcher Dr Lennert Veerman said the WHO recommended physical activity of 10 metabolic equivalent (MET) hours a week.

    "So that's the equivalent of about 1.75 hours of running or two, three hours of walking briskly [a week]," he said.

    "But the study found health gains accumulated up to the levels of 50 to 70 MET hours a week.

    "That's the equivalent of 15-20 hours of brisk walking or 6-8 hours of running [a week].





    Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review and dose-response meta-analysis for the Global Burden of Disease Study 2013

    BMJ 2016; 354 doi: http://dx.doi.org/10.1136/bmj.i3857 (Published 09 August 2016) Cite this as: BMJ 2016;354:i3857


    Hmwe H Kyu, acting assistant professor1, Victoria F Bachman, medical student2, Lily T Alexander, post bachelor fellow1, John Everett Mumford, post bachelor fellow1, Ashkan Afshin, acting assistant professor1, Kara Estep, project officer II1, J Lennert Veerman, senior lecturer3, Kristen Delwiche, medical student4, Marissa L Iannarone, project officer1, Madeline L Moyer, systematic reviewer1, Kelly Cercy, data analyst1, Theo Vos, professor1, Christopher J L Murray, professor1, Mohammad H Forouzanfar, assistant professor1




    Objective To quantify the dose-response associations between total physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events.



    Design Systematic review and Bayesian dose-response meta-analysis.


    Data sources PubMed and Embase from 1980 to 27 February 2016, and references from relevant systematic reviews. Data from the Study on Global AGEing and Adult Health conducted in China, Ghana, India, Mexico, Russia, and South Africa from 2007 to 2010 and the US National Health and Nutrition Examination Surveys from 1999 to 2011 were used to map domain specific physical activity (reported in included studies) to total activity.


    Eligibility criteria for selecting studies Prospective cohort studies examining the associations between physical activity (any domain) and at least one of the five diseases studied.


    Results 174 articles were identified: 35 for breast cancer, 19 for colon cancer, 55 for diabetes, 43 for ischemic heart disease, and 26 for ischemic stroke (some articles included multiple outcomes). Although higher levels of total physical activity were significantly associated with lower risk for all outcomes, major gains occurred at lower levels of activity (up to 3000-4000 metabolic equivalent (MET) minutes/week). For example, individuals with a total activity level of 600 MET minutes/week (the minimum recommended level) had a 2% lower risk of diabetes compared with those reporting no physical activity. An increase from 600 to 3600 MET minutes/week reduced the risk by an additional 19%. The same amount of increase yielded much smaller returns at higher levels of activity: an increase of total activity from 9000 to 12 000 MET minutes/week reduced the risk of diabetes by only 0.6%. Compared with insufficiently active individuals (total activity <600 MET minutes/week), the risk reduction for those in the highly active category (≥8000 MET minutes/week) was 14% (relative risk 0.863, 95% uncertainty interval 0.829 to 0.900) for breast cancer; 21% (0.789, 0.735 to 0.850) for colon cancer; 28% (0.722, 0.678 to 0.768) for diabetes; 25% (0.754, 0.704 to 0.809) for ischemic heart disease; and 26% (0.736, 0.659 to 0.811) for ischemic stroke.


    Conclusions People who achieve total physical activity levels several times higher than the current recommended minimum level have a significant reduction in the risk of the five diseases studied. More studies with detailed quantification of total physical activity will help to find more precise relative risk estimates for different levels of activity.


  5. Some studies examining the evidence(or lack thereof) for routine 6-monthly dental check-ups:


    1. Br Dent J. 2003 Jul 26;195(2):87-98; discussion 85.


    The effectiveness of routine dental checks: a systematic review of the evidence



    Davenport CF(1), Elley KM, Fry-Smith A, Taylor-Weetman CL, Taylor RS.


    Author information:

    (1)Department of Public Health and Epidemiology, University of Birmingham,

    Edgbaston, Birmingham B15 2TT. C.F.Davenport@bham.ac.uk


    Comment in

    Br Dent J. 2004 Feb 28;196(4):187; author reply 187.

    Br Dent J. 2003 Jul 26;195(2):63.


    AIMS: To systematically review the effectiveness of routine dental checks of

    different recall frequencies in adults and children.


    METHODS: Search methods included electronic bibliographic databases up to March

    2001, relevant internet sites, citation checking and contact with experts and

    professional dental bodies.


    INCLUSION CRITERIA: (1) STUDY DESIGN: any; (2) POPULATION: deciduous, mixed and

    permanent dentition; (3) INTERVENTION: 'Routine dental check': 'clinical

    examination, advice, charting (including monitoring of periodontal status) and

    report' as defined in the NHS Executive General Dental Service Statement of

    Dental Remuneration; (4) Comparator: no routine dental check or routine dental

    check(s) of different recall frequency; (5) PRIMARY OUTCOMES: caries, periodontal

    disease, quality of life, oral cancer.


    RESULTS: Twenty eight studies were identified for the review. Studies were poorly

    reported and clinically heterogenous which restricted comparison between studies

    and limited generalisability to the UK situation. There was no consistency across

    multiple studies in the direction of effect of different dental check frequencies

    on measures of caries in deciduous mixed or permanent dentition, periodontal

    disease or oral cancer in permanent dentition. No studies were identified linking

    empirical measures of quality of life associated with oral health and dental

    check frequency.


    CONCLUSIONS: There is no existing high quality evidence to support or refute the

    practice of encouraging six-monthly dental checks in adults and children.


    DOI: 10.1038/sj.bdj.4810337

    PMID: 12881749 [PubMed - indexed for MEDLINE]




    1. Evid Based Dent. 2005;6(3):62-3.


    Insufficient evidence to support or refute the need for 6-monthly dental

    check-ups. What is the optimal recall frequency between dental checks?


    Mettes D(1).


    Author information:

    (1)College of Oral Sciences, Radboud University Nijmegen (formerly University of

    Nijmegen) Medical Centre, Nijmegen, The Netherlands.


    Comment on

    Cochrane Database Syst Rev. 2005;(2):CD004346.


    DATA SOURCES: Trials were sourced using the Cochrane Oral Health Group Trials

    Register, the Cochrane Central Register of Controlled Trials, Medline and Embase.

    Reference lists from relevant articles were scanned and the authors of some

    papers were contacted to identify further trials and obtain additional



    STUDY SELECTION: Trials were selected if they met the following criteria:design:

    random allocation of participants;participants: all children and adults receiving

    dental check-ups in primary-care settings, irrespective of their level of risk

    for oral disease;interventions: recall intervals for either clinical examination

    only, clinical examination plus scale and polish, clinical examination plus

    preventive advice, clinical examination plus scale and polish plus preventive

    advice, no recall interval/patient-driven attendance (which may be symptomatic),

    or clinician risk-based recall intervals;outcomes: clinical status outcomes for

    dental caries including, but not limited to, mean dmft/DMFT, dmfs/DMFS scores,

    caries increment, filled teeth (including replacement restorations), early

    carious lesions (arrested or reversed); periodontal disease (including, but not

    limited to, plaque, calculus, gingivitis, periodontitis, change in probing depth,

    and attachment level); oral mucosa (presence or absence of mucosal lesions,

    potentially malignant lesions, cancerous lesions, and size and stage of cancerous

    lesions at diagnosis). In addition, the following outcomes were considered where

    reported: patient-centred outcomes, economic-cost outcomes, other outcomes such

    as improvements in oral health knowledge and attitudes, harms, changes in dietary

    habits, and any other oral health-related behavioural change.


    DATA EXTRACTION AND SYNTHESIS: Information regarding methods, participants,

    interventions, outcome measures, and results were independently extracted, in

    duplicate, by two authors. Authors were contacted, where deemed necessary and

    where possible, for further details regarding study design and for data

    clarification. A quality assessment of the included trial was carried out. The

    Cochrane Oral Health Group's statistical guidelines were followed.


    RESULTS: Only one study (with 188 participants) was included in this review and

    was assessed as having a high risk of bias. This study provided limited data for

    dental caries outcomes (dmfs/DMFS increment) and economic cost outcomes (reported

    time taken to provide examinations and treatment).


    CONCLUSIONS: There is insufficient evidence from randomised controlled trials

    (RCT) to draw any conclusions regarding the potential beneficial and harmful

    effects of altering the recall interval between dental check-ups. There is

    insufficient evidence to support or refute the practice of encouraging patients

    to attend for dental check-ups at 6-monthly intervals. It is important that high

    quality RCT are conducted for the outcomes listed in this review in order to

    address its objectives.


    DOI: 10.1038/sj.ebd.6400341

    PMID: 16184154 [PubMed]




    1. Cochrane Database Syst Rev. 2013 Dec 19;(12):CD004346. doi:



    Recall intervals for oral health in primary care patients.


    Riley P(1), Worthington HV, Clarkson JE, Beirne PV.


    Author information:

    (1)Cochrane Oral Health Group, School of Dentistry, The University of Manchester,

    Coupland III Building, Oxford Road, Manchester, UK, M13 9PL.


    Comment in

    Evid Based Dent. 2014 Jun;15(2):40.


    Update of

    Cochrane Database Syst Rev. 2007;(4):CD004346.


    BACKGROUND: The frequency with which patients should attend for a dental check-up

    and the potential effects on oral health of altering recall intervals between

    check-ups have been the subject of ongoing international debate in recent

    decades. Although recommendations regarding optimal recall intervals vary between

    countries and dental healthcare systems, six-monthly dental check-ups have

    traditionally been advocated by general dental practitioners in many developed

    countries.This is an update of a Cochrane review first published in 2005, and

    previously updated in 2007.


    OBJECTIVES: To determine the beneficial and harmful effects of different fixed

    recall intervals (for example six months versus 12 months) for the following

    different types of dental check-up: a) clinical examination only; b) clinical

    examination plus scale and polish; c) clinical examination plus preventive

    advice; d) clinical examination plus preventive advice plus scale and polish.To

    determine the relative beneficial and harmful effects between any of these

    different types of dental check-up at the same fixed recall interval.To compare

    the beneficial and harmful effects of recall intervals based on clinicians'

    assessment of patients' disease risk with fixed recall intervals.To compare the

    beneficial and harmful effects of no recall interval/patient driven attendance

    (which may be symptomatic) with fixed recall intervals.


    SEARCH METHODS: The following electronic databases were searched: the Cochrane

    Oral Health Group's Trials Register (to 27 September 2013), the Cochrane Central

    Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 9),

    MEDLINE via OVID (1946 to 27 September 2013) and EMBASE via OVID (1980 to 27

    September 2013). We searched the US National Institutes of Health Trials Register

    (http://clinicaltrials.gov) and the WHO International Clinical Trials Registry

    Platform (http://www.who.int/ictrp/en/) for ongoing trials. Reference lists from

    relevant articles were scanned and the authors of some papers were contacted to

    identify further trials and obtain additional information. We did not apply any

    restrictions regarding language or date of publication when searching the

    electronic databases.


    SELECTION CRITERIA: We included randomised controlled trials (RCTs) assessing the

    effects of different dental recall intervals.


    DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the

    search results against the inclusion criteria of the review, extracted data and

    carried out risk of bias assessment. We contacted study authors for clarification

    or further information where necessary and feasible. If we had found more than

    one study with similar comparisons reporting the same outcomes, we would have

    combined the studies in a meta-analysis using a random-effects model if there

    were at least four studies, or a fixed-effect model if there were less than four

    studies. We expressed the estimate of effect as mean difference with 95%

    confidence intervals (CIs) for continuous outcomes. We would have used risk

    ratios with 95% CI for any dichotomous outcomes.


    MAIN RESULTS: We included one study that analysed 185 participants. The study

    compared the effects of a clinical examination every 12 months with a clinical

    examination every 24 months on the outcomes of caries (decayed, missing, filled

    surfaces (dmfs/DMFS) increment) and economic cost outcomes (total time used per

    person). As the study was at high risk of bias, had a small sample size and only

    included low-risk participants, we rated the quality of the body of evidence for

    these outcomes as very low.For three to five-year olds with primary teeth, the

    mean difference (MD) in dmfs increment was -0.90 (95% CI -1.96 to 0.16) in favour

    of 12-month recall. For 16 to 20-year olds with permanent teeth, the MD in DMFS

    increment was -0.86 (95% CI -1.75 to 0.03) also in favour of 12-month recall.

    There is insufficient evidence to determine whether 12 or 24-month recall with

    clinical examination results in better caries outcomes.For three to five-year

    olds with primary teeth, the MD in time used by each participant was 10 minutes

    (95% CI -6.7 to 26.7) in favour of 24-month recall. For 16 to 20-year olds with

    permanent teeth, the MD was 23.7 minutes (95% CI 4.12 to 43.28) also in favour of

    24-month recall. This single study at high risk of bias represents insufficient

    evidence to determine whether 12 or 24-month recall with clinical examination

    results in better time/cost outcomes.


    AUTHORS' CONCLUSIONS: There is a very low quality body of evidence from one RCT

    which is insufficient to draw any conclusions regarding the potential beneficial

    and harmful effects of altering the recall interval between dental check-ups.

    There is no evidence to support or refute the practice of encouraging patients to

    attend for dental check-ups at six-monthly intervals. It is important that high

    quality RCTs are conducted for the outcomes listed in this review in order to

    address the objectives of this review.


    DOI: 10.1002/14651858.CD004346.pub4

    PMID: 24353242 [PubMed - indexed for MEDLINE]


  6. Brett,


    I think one of the comments on the Longecity thread about the first study (PMID: 19426179) are likely on the money. If you floss someone's teeth who regularly doesn't floss (particularly when a hygienist does it who doesn't know how hard they need to push down to get the floss between two teeth) then:

    • There is likely to be a lot of bacteria build up between teeth.
    • Their gums aren't used to being rubbed and so will likely bleed.
    The combination will naturally lead to bacteria getting into the bloodstream. But when you floss regularly, correctly, and gently, gums don't bleed (at least that's my experience), and there is little bacteria build up to get into the bloodstream even if they did.





    Sure, that may be a possibility, but obviously it's speculation. My past reading on these and related issues suggested to me that there is a lack of quality evidence surrounding common dental hygiene practices in general. Thus speculation and hypothesis may be necessary guiding forces unfortunately. If I recall correctly, other comments on the Longecity thread mentioned bacteremia resulting from teeth brushing and even eating. So bacteremia induction may not require unusual/unaccustomed gum stresses. Of course, even if bacteremia is a common daily occurence resulting from everyday living, that doesn't mean it's desirable. Here's a study that showed bacteremia from toothbrushing alone, with powered toothbrushing inducing more bacteremia than manual toothbrushing:


    1. Pediatr Dent. 2002 Jul-Aug;24(4):295-9.


    Transient bacteremia induced by toothbrushing a comparison of the Sonicare

    toothbrush with a conventional toothbrush.


    Bhanji S(1), Williams B, Sheller B, Elwood T, Mancl L.


    Author information:

    (1)Dental Medicine, Children's Hospital, Seattle, Wash, USA. shamib@hotmail.com


    PURPOSE: Several investigations have demonstrated toothbrush-induced bacteremias.

    Transient bacteremias are well tolerated by healthy individuals but may increase

    endocarditis risk in patients with cardiac conditions. This study assessed

    bacteremia levels after brushing with either the Sonicare electric toothbrush or

    a manual toothbrush.


    METHODS: Fifty healthy children receiving dental treatment under general

    anesthesia with oral intubation were randomly assigned to a manual or Sonicare

    group. Plaque levels and gingival health were scored and a blood sample

    collected. Teeth were brushed for 1 minute and a postbrushing blood sample was

    drawn. Samples were analyzed for aerobic and anaerobic bacterial growth.


    RESULTS: Gingival health and plaque scores did not differ between groups. No

    correlation was detected between plaque and gingival scores and occurrence of

    bacteremia. The frequency of bacteremia was 46% with manual brushing: 18%

    aerobic, 9% anaerobic and 73% both. This differed significantly (P = .022) with

    78% bacteremias in the Sonicare group: 22% aerobic, 22% anaerobic and 56% both.


    CONCLUSIONS: The Sonicare induced significantly more bacteremias than manual

    toothbrushing. These results show that vigorous brushing increased bacteremia

    from one brushing but does not answer whether bacteremia incidence would decrease

    with a program of vigorous daily brushing; this should be clarified before

    recommending brushing methods for patients with compromised cardiac conditions.

    PMID: 12212870 [PubMed - indexed for MEDLINE]


  7. This meta-analysis concludes that there is a lack of scientific evidence to support routinely recommending flossing:


    1. Int J Dent Hyg. 2008 Nov;6(4):265-79. doi: 10.1111/j.1601-5037.2008.00336.x.


    The efficacy of dental floss in addition to a toothbrush on plaque and parameters

    of gingival inflammation: a systematic review.


    Berchier CE(1), Slot DE, Haps S, Van der Weijden GA.


    Author information:

    (1)School of Dental Hygiene, INHOLLAND University for Applied Sciences,

    Amsterdam, The Netherlands.


    Comment in

    Int J Dent Hyg. 2008 Nov;6(4):251-2.


    OBJECTIVES: The aim of this study was to assess systematically the adjunctive

    effect of both flossing and toothbrushing versus toothbrushing alone on plaque

    and gingivitis.

    MATERIALS: The MEDLINE and Cochrane Central register of Controlled Trials

    (CENTRAL) databases were searched through December 2007 to identify appropriate

    studies. The variables of plaque and gingivitis were selected as outcomes.

    RESULTS: Independent screening of titles and abstracts of 1166 MEDLINE-Pubmed and

    187 Cochrane papers resulted in 11 publications that met the eligibility

    criteria. Mean values and SD were collected by data extraction. Descriptive

    comparisons are presented for brushing alone or brushing and flossing. A greater

    part of the studies did not show a benefit for floss on plaque and clinical

    parameters of gingivitis. A meta-analysis was performed for the plaque index and

    gingival index.

    CONCLUSIONS: The dental professional should determine, on an individual patient

    basis, whether high-quality flossing is an achievable goal. In light of the

    results of this comprehensive literature search and critical analysis, it is

    concluded that a routine instruction to use floss is not supported by scientific



    DOI: 10.1111/j.1601-5037.2008.00336.x

    PMID: 19138178 [PubMed - indexed for MEDLINE]


  8. Flossing may cause gum tissue trauma leading to oral bacteria transmission into the bloodstream ("bacteraemia"):


    1. J Clin Periodontol. 2009 Apr;36(4):323-32. doi: 10.1111/j.1600-051X.2008.01372.x.

    Epub 2009 Mar 11.


    Bacteraemia due to dental flossing.


    Crasta K(1), Daly CG, Mitchell D, Curtis B, Stewart D, Heitz-Mayfield LJ.


    Author information:

    (1)Discipline of Periodontics, Faculty of Dentistry, University of Sydney, NSW,



    AIMS: The aims of this study were to (1) investigate the incidence of bacteraemia

    following flossing in subjects with chronic periodontitis or periodontal health;

    (2) identify the micro-organisms in detected bacteraemias; and (3) identify any

    patient or clinical factors associated with such bacteraemia.

    MATERIAL AND METHODS: Baseline blood samples were obtained from 30 individuals

    with chronic periodontitis (17 M:13 F, 29-75 years) and 30 with periodontal

    health (17 M:13 F, 28-71 years) following a non-invasive examination. Each

    subject's teeth were then flossed in a standardized manner and blood samples

    obtained 30 s and 10 min. after flossing cessation. Blood samples were cultured

    in a BACTEC system and positive samples subcultured for identification.

    RESULTS: Forty per cent of periodontitis subjects and 41% of periodontally

    healthy subjects tested positive for bacteraemia following flossing. Viridans

    streptococci, which are commonly implicated in infective endocarditis (IE), were

    isolated from 19% of positive subjects and accounted for 35% of microbial

    isolates. Twenty per cent of subjects had a detectable bacteraemia at 10 min.

    post-flossing. No patient or clinical factors were significantly associated with

    post-flossing bacteraemia.

    CONCLUSIONS: Dental flossing can produce bacteraemia in periodontally healthy and

    periodontally diseased individuals at a rate comparable with that caused by some

    dental treatments for which antibiotic prophylaxis is given to prevent IE.


    DOI: 10.1111/j.1600-051X.2008.01372.x

    PMID: 19426179 [PubMed - indexed for MEDLINE]


  9. 1. Aging Cell. 2016 Jun 16. doi: 10.1111/acel.12496. [Epub ahead of print]


    Longer lifespan in male mice treated with a weakly estrogenic agonist, an

    antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer.


    Strong R(1,)(2), Miller RA(3), Antebi A(4), Astle CM(5), Bogue M(5), Denzel

    MS(4), Fernandez E(1,)(2), Flurkey K(5), Hamilton KL(6), Lamming DW(7), Javors

    MA(8), de Magalhães JP(9), Martinez PA(1,)(2), McCord JM(10), Miller BF(6),

    Müller M(11), Nelson JF(12), Ndukum J(5), Rainger GE(13), Richardson A(14,)(15),

    Sabatini DM(16,)(17,)(18,)(19,)(20), Salmon AB(21), Simpkins JW(22), Steegenga

    WT(23), Nadon NL(24), Harrison DE(5).


    Author information:

    (1)Geriatric Research, Education and Clinical Center and Research Service, South

    Texas Veterans Health Care System, Department of Pharmacology, The University of

    Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.

    (2)Barshop Institute for Longevity and Aging Studies, The University of Texas

    Health Science Center at San Antonio, San Antonio, TX, 78229, USA. (3)Department

    of Pathology and Geriatrics Center, University of Michigan, Ann Arbor, MI,

    48109-2200, USA. (4)Max Planck Institute for Biology of Ageing, Cologne, D-50931,

    Germany. (5)The Jackson Laboratory, Bar Harbor, ME, 04609, USA. (6)Colorado State

    University, Fort Collins, CO, 80523, USA. (7)Department of Medicine, University

    of Wisconsin-Madison, Madison, WI, 53705, USA. (8)Department of Psychiatry,

    University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229,

    USA. (9)School of Biological Sciences, University of Liverpool, Crown Street,

    Liverpool, L69 7ZB, UK. (10)Division of Pulmonary Sciences and Critical Care

    Medicine, University of Colorado, Aurora, CO, USA. (11)Norwich Medical School,

    University of East Anglia, Norwich, UK. (12)Department of Physiology and Barshop

    Center for Longevity and Aging Studies, The University of Texas Health Science

    Center at San Antonio, San Antonio, TX, 78229, USA. (13)Centre for Cardiovascular

    Sciences, School of Clinical and Experimental Medicine, The Medical School, The

    University of Birmingham, Birmingham, UK. (14)Department of Geriatric Medicine,

    University of Oklahoma Health Science Center, Oklahoma City, OK, 73104, USA.

    (15)VA Medical Center, Oklahoma City, OK, 73104, USA. (16)Whitehead Institute for

    Biomedical Research, Cambridge, MA, 02142, USA. (17)Department of Biology, MIT,

    Cambridge, MA, 02139, USA. (18)Howard Hughes Medical Institute, MIT, Cambridge,

    MA, 02139, USA. (19)Broad Institute of Harvard and MIT, Seven Cambridge Center,

    Cambridge, MA, 02142, USA. (20)The David H. Koch Institute for Integrative Cancer

    Research at MIT, Cambridge, MA, 02139, USA. (21)Department of Molecular Medicine

    and Barshop Institute for Longevity and Aging Studies, The University of Texas

    Health Science Center at San Antonio, San Antonio, TX, 78229, USA. (22)Center for

    Basic & Translational Stroke Research, West Virginia University, Morgantown, WV,

    26506, USA. (23)Division of Human Nutrition, Wageningen University and Research

    Centre, Wageningen, The Netherlands. (24)Division of Aging Biology, National

    Institute on Aging, Bethesda, MD, 20892, USA.


    The National Institute on Aging Interventions Testing Program (ITP) evaluates

    agents hypothesized to increase healthy lifespan in genetically heterogeneous

    mice. Each compound is tested in parallel at three sites, and all results are

    published. We report the effects of lifelong treatment of mice with four agents

    not previously tested: Protandim, fish oil, ursodeoxycholic acid (UDCA) and

    metformin - the latter with and without rapamycin, and two drugs previously

    examined: 17-α-estradiol and nordihydroguaiaretic acid (NDGA), at doses greater

    and less than used previously. 17-α-estradiol at a threefold higher dose robustly

    extended both median and maximal lifespan, but still only in males. The

    male-specific extension of median lifespan by NDGA was replicated at the original

    dose, and using doses threefold lower and higher. The effects of NDGA were dose

    dependent and male specific but without an effect on maximal lifespan. Protandim,

    a mixture of botanical extracts that activate Nrf2, extended median lifespan in

    males only. Metformin alone, at a dose of 0.1% in the diet, did not significantly

    extend lifespan. Metformin (0.1%) combined with rapamycin (14 ppm) robustly

    extended lifespan, suggestive of an added benefit, based on historical comparison

    with earlier studies of rapamycin given alone. The α-glucosidase inhibitor,

    acarbose, at a concentration previously tested (1000 ppm), significantly

    increased median longevity in males and 90th percentile lifespan in both sexes,

    even when treatment was started at 16 months. Neither fish oil nor UDCA extended

    lifespan. These results underscore the reproducibility of ITP longevity studies

    and illustrate the importance of identifying optimal doses in lifespan studies.


    © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley

    & Sons Ltd.


    DOI: 10.1111/acel.12496

    PMID: 27312235 [PubMed - as supplied by publisher]




  10. Here's a patent that describes treatment with widely used and available antiviral drugs to reduce the impact of CMV infection on the immune system:



    Use of antivirals to treat cmv-related conditions

    US 20100280052 A1
    The invention provides for the use of compounds active against cytomegalovirus (CMV) in the preparation of medicaments for improving the immune response of a CMV-seropositive, immunocompetent individual, or for the amelioration of certain other medical conditions. Suitable compounds include the nucleoside analogues acyclovir, famciclovir, and valacyclovir. Infection with cytomegalovirus is widespread and commonly believed to be both asymptomatic in immunocompetent individuals and unbeatable without the use of highly cytotoxic drugs. It is suggested herein that, in fact, CMV infection produces a disproportionately large immune response, thereby weakening the ability of the immune system to respond to other infections (and hence is not asymptomatic). Further, treatment with comparatively low doses of drugs having low cytotoxicity (and hence similarly low efficacy) can reduce the magnitude of this CMV-specific immune response, improving the overall immune response, and ameliorating the symptoms of other medical conditions.


  11. Who says the meaning/purpose in my(and your?) life is "merely" "subjective" "arbitrary" "preference"? My meaning, all meaning, is part of the very fabric and essence of existence. And, I am, after all, existence itself. Claiming any of this is arbitrary, assumes that there could be some alternative way things could be - but this is nonsense. What is, is what is - end of story. No imaginary God could claim any greater.


    It's kind of pathetic to see how self-denying...self-negating...most everyone is. Like a bunch of sick ascetics or something. Are you all gonna start whipping yourselves soon too? I suppose it's an outgrowth of social control. Now God's gone, society has had to fashion a new method to maintain control: the postmodern "that's only your opinion!" to keep people in line works nicely. The ultimate in low self-esteem is hammered into you - you can't even trust your own meaning, purpose, LIFE. Ha! No thanks - I retain my godhood.


    Furthermore: egoism combined with empathy can combine to form something like Peter Singer's "Point of View of the Universe" - there need be no contradiction there. I feel your pain, and because I don't like being in pain I don't want you to be in pain. Simple. Empathy aligns with the apparent reality of other beings' capacity to feel pain/pleasure, making empathy an accurate, instinctual-level, representation/reflection of reality. Then, right = pleasure and wrong = pain. "Right" and "wrong" being more complex manifestations/representations of pleasure/pain.

  12. The lack of mortality benefit seen in the EPIC-Oxford vegetarians/vegans might be due to bias from the "healthy volunteer" effect among the non-vegetarians/vegans. It looks like the vegetarians/vegans still managed around half the expected death rate of the general population[1]:




    In the EPIC-Oxford study, there was no difference in all-cause mortality between vegetarians and nonvegetarians (HR: 1.05; 95% CI: 0.93, 1.19), although the overall death rate was only one-half that of the United Kingdom population as a whole




    Dean, do you know about www.veganhealth.org? It's got to be one of the best science-based websites relating to veganism. Here's a veganhealth.org page that collected mortality data of vegans from several studies:


  13. The result was interesting:  Urine Hg, Pb, etc. were vanishingly low.  BUT --- surprise! --- urinary Arsenic was high normal!  (The figure was well within the acceptable range -- but higher than the 50'th percentile).  Neither Dr. Taylor (my nephrologist) nor I have any idea why.




      -- Saul


    Do you eat rice or rice-derived products? There have been some concerns raised about arsenic levels in rice, e.g.:


  14. Interesting recent study investigating many variables (including gut microbiota) that may impact glycemic response to meals, suggesting that the use of stock glycemic index food tables may provide limited predictive power:


    1. Cell. 2015 Nov 19;163(5):1079-94. doi: 10.1016/j.cell.2015.11.001.


    Personalized Nutrition by Prediction of Glycemic Responses.


    Zeevi D(1), Korem T(1), Zmora N(2), Israeli D(3), Rothschild D(1), Weinberger

    A(1), Ben-Yacov O(1), Lador D(1), Avnit-Sagi T(1), Lotan-Pompan M(1), Suez J(4),

    Mahdi JA(4), Matot E(1), Malka G(1), Kosower N(1), Rein M(1), Zilberman-Schapira

    G(4), Dohnalová L(4), Pevsner-Fischer M(4), Bikovsky R(1), Halpern Z(5), Elinav

    E(6), Segal E(7).


    Author information:

    (1)Department of Computer Science and Applied Mathematics, Weizmann Institute of

    Science, Rehovot 7610001, Israel; Department of Molecular Cell Biology, Weizmann

    Institute of Science, Rehovot 7610001, Israel. (2)Immunology Department, Weizmann

    Institute of Science, Rehovot 7610001, Israel; Internal Medicine Department, Tel

    Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel; Research Center for

    Digestive Tract and Liver Diseases, Tel Aviv Sourasky Medical Center, Sackler

    Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, Israel. (3)Day Care

    Unit and the Laboratory of Imaging and Brain Stimulation, Kfar Shaul Hospital,

    Jerusalem Center for Mental Health, Jerusalem 9106000, Israel. (4)Immunology

    Department, Weizmann Institute of Science, Rehovot 7610001, Israel. (5)Research

    Center for Digestive Tract and Liver Diseases, Tel Aviv Sourasky Medical Center,

    Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, Israel;

    Digestive Center, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel.

    (6)Immunology Department, Weizmann Institute of Science, Rehovot 7610001, Israel.

    Electronic address: eran.elinav@weizmann.ac.il. (7)Department of Computer Science

    and Applied Mathematics, Weizmann Institute of Science, Rehovot 7610001, Israel;

    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot

    7610001, Israel. Electronic address: eran.segal@weizmann.ac.il.


    Elevated postprandial blood glucose levels constitute a global epidemic and a

    major risk factor for prediabetes and type II diabetes, but existing dietary

    methods for controlling them have limited efficacy. Here, we continuously

    monitored week-long glucose levels in an 800-person cohort, measured responses to

    46,898 meals, and found high variability in the response to identical meals,

    suggesting that universal dietary recommendations may have limited utility. We

    devised a machine-learning algorithm that integrates blood parameters, dietary

    habits, anthropometrics, physical activity, and gut microbiota measured in this

    cohort and showed that it accurately predicts personalized postprandial glycemic

    response to real-life meals. We validated these predictions in an independent

    100-person cohort. Finally, a blinded randomized controlled dietary intervention

    based on this algorithm resulted in significantly lower postprandial responses

    and consistent alterations to gut microbiota configuration. Together, our results

    suggest that personalized diets may successfully modify elevated postprandial

    blood glucose and its metabolic consequences. VIDEO ABSTRACT.


    Copyright © 2015 Elsevier Inc. All rights reserved.


    PMID: 26590418 [PubMed - in process]




  15. My impression is still that evidence for IGF-1 impact on human longevity is inconsistent and unclear. I think the reviews from the experts agree with that position. I'm not sure speculations about IGF-1-related longevity in humans, currently largely extrapolated from mice, worms and yeast, through unspecified "anti-aging" mechanisms, should enter the equation when better human evidence supports protection or risk for specific pathologies of aging. When we look beyond mice, the lack of observed longevity benefits in IGF-1 deficient human Laron dwarfs and CR'ed rhesus monkeys adds further uncertainty about the translatability to humans.

    IGF-1 genetic association studies may not be applicable to diet-induced IGF-1 levels in adults if longevity benefits mainly derive from exposure during develpomental years of life. Another element of potential importance for some CR practitioners is that impaired glucose tolerance may be a significant CVD and stroke risk factor. This is not necessarily an either/or situation, as one doesn't require CR or lower protein diet to maintain a superb CVD risk profile. There may be alternative ways to lower risk of cancer too, like a plant-based diet, which has been shown to blunt the dietary protein/IGF-1/cancer association.

    One option is to look at the IGF-1 issue from a personal risk factor perspective: those with higher risk for cancer maybe should opt for lower IGF-1, those with higher risk for cardiovascular and cerebrovascular diseases and concern for maintaining bone, brain and muscle health maybe should opt for higher IGF-1.


    1. Curr Vasc Pharmacol. 2014;12(5):674-81.

    Association between genetic variations in the insulin/insulin-like growth factor
    (Igf-1) signaling pathway and longevity: a systematic review and meta-analysis.

    Di Bona D, Accardi G, Virruso C, Candore G, Caruso C(1).

    Author information:
    (1)U.O. di Medicina Trasfusionale, AOUP Paolo Giaccone, Via del Vespro 129, 90127
    Palermo, Italy. danilodibona@yahoo.it.

    Some studies have shown that polymorphisms in the insulin growth factor-1 (IGF-1)
    signaling pathway genes could influence human longevity. However, the results of
    different studies are often inconsistent. Our aim was to investigate by
    systematic review and meta-analysis the association of the common polymorphisms
    defining the genetic variability of the IGF-1 signaling pathway associated with
    human longevity. Eleven studies investigating the association between the
    polymorphisms in the IGF-1 signaling pathway genes (IGF-1, IGF-1 receptor
    (IGF-1R), Forkhead box O3A (FOXO3A) and Silent mating type Information Regulation
    1 (SIRT1) and longevity were found and analyzed. The modelfree approach was
    applied to meta-analyze these studies. No association was reported between the
    single nucleotide polymorphisms (SNPs) of IGF-1 and longevity in the only
    available study. The meta-analysis of available data from four studies, showed a
    significant association with the IGF-1R polymorphism rs2229765, suggesting that
    subjects with the Abearing genotype have a greater chance of longevity.
    Concerning the five studies on FOXO3A SNPs, for the rs2764264 a significant
    association with longevity was observed for C allele when only males were
    included in the analysis. Statistically significant results were obtained for
    other SNPs as well, i.e. rs2802292 (G allele), rs9400239 and rs479744 (T and A
    alleles, respectively). For rs9400239 the association was observed in long lived
    males with a lower odds ratio than in centenarians, while in rs479744 a
    significant association was highlighted in centenarians. Concerning SIRT1, no
    association between the SNPs under study and longevity was observed in the only
    available report. Current findings suggest that both IGF-1R and FOXO3A
    polymorphisms could be associated with longevity. The high degree of
    between-study heterogeneity and the low number of available studies underline the
    need for further methodologically adequate analyses to confirm this evidence.

    PMID: 24350933  [PubMed - indexed for MEDLINE]


  16. Additionally, there is the concern around BPA and many of its substitutes

    Slightly off topic, but I know you have expressed concerns about BPA leaching into food from packaging in the past, and I know you also drink(or at least drank) wine, so I thought this might interest you too:


    1. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2014;31(9):1605-15.

    doi: 10.1080/19440049.2014.941947. Epub 2014 Aug 7.


    Contamination of wines and spirits by phthalates: types of contaminants present,

    contamination sources and means of prevention.


    Chatonnet P(1), Boutou S, Plana A.


    Author information:

    (1)a Laboratoire Excell , Parc Innolin , 33700 Mérignac , France.


    This research determines the concentrations of various phthalates in French wines

    and grape spirits marketed in Europe or intended for export. Dibutyl phthalate

    (DBP), diethylhexyl phthalate (DEHP) and butyl benzyl phthalate (BBP) were the

    most frequently detected compounds in the wines analysed. While only 15% of the

    samples examined contained quantifiable concentrations (> 0.010 mg kg(-1)) of

    DEHP and BBP, 59% of the wines contained significant quantities of DBP, with a

    median value as high as 0.0587 mg kg(-1). Only 17% of the samples did not contain

    any detectable quantity of at least one of the phthalates and 19% contained only

    non-quantifiable traces. In the spirits analysed, DBP (median = 0.105 mg kg(-1))

    and DEHP (median = 0.353 mg kg(-1)) were the substances measured at the highest

    concentrations, as well as the most frequently detected (90% of samples). BBP was

    present in 40% of the samples at an average concentration of 0.026 mg kg(-1).

    Di-isobutyl phthalate (DiBP), which is not permitted in contact with food, was

    found in 25% of the spirits tested. According to the specific migration limits

    (SML) for materials in contact with food, slightly more than 11% of the wines

    analysed were non-compliant, as they exceeded the SML for DBP (0.3 mg kg(-1));

    just under 4% were close to the SML for DEHP. Concerning spirits, 19% of the

    samples analysed were considered non-compliant to the SML for DBP and nearly 7%

    were close to the SML for DEHP. The aged grape spirits analysed were often

    excessively contaminated with DiBP, which is not permitted to be used in contact

    with food (> 0.01 mg kg(-1)). A study of various materials frequently present in

    wineries revealed that a relatively large number of polymers sometimes contained

    high concentrations of phthalates. However, the epoxy resin coatings used on vats

    represented the major source of contamination.


    PMID: 25099435 [PubMed - indexed for MEDLINE]


    A discussion about the study findings and some comments from posters claiming to have in-depth technical knowledge of industrial-scale wine production methods and where and how phthalates might be getting into the wine:


  17. There is no clear evidence of longevity benefits of lower IGF-1 in humans, the current evidence is contradictory. Laron dwarfism in humans, which results in congenitally low IGF-1 (and which resembles the longevous genetically-modifed IGF-1 deficient rodent models) has not been observed to result in unusually long lives.


    Among other things, lower IGF-1 may reduce risk of cancer mortality, and since many(most?) common laboratory mice strains have high mortality due to cancer (think 90%) this may largely explain the benefit seen in mice. However, lower IGF-1 may, among other things, increase risk of mortality from cardiovascular diseases, and whilst cardiovascular mortality is not a significant threat in mice, it is in humans. Basically, the benefits and detriments of higher or lower IGF-1 may be species, strain and disease specific.


    There is also evidence that the lifespan benefits seen in mice from lower IGF-1/GH may only be realized when they are kept low during early life (equivalent perhaps to the childhood/adolescent years in humans.)


    Some of the issues reported by and personally concerning calorie restriction practitioners (e.g. bone health, impaired glucose tolerance) might benefit from increased IGF-1. Just generally IGF-1 and its anabolic growth and repair-inducing effects may oppose many of the common and serious quality-of-life problems associated with aging including cognitive decline, muscle wasting, cardiovascular dysfunction, skin aging etc and I think it is something that should be considered very carefully.


    Dean (and anyone else interested), I can't recommend highly enough reading the first paper I have linked to below. It contains a wealth of very interesting and potentially important information regarding IGF-1 and its relation to lifespan, healthspan and disease in both humans and rodents.



    "Diverse Roles of Growth Hormone and Insulin-Like Growth Factor-1 in Mammalian Aging: Progress and Controversies"



    "Recent landmark studies from Panici et al. indicate that administration of GH from day 14 for 6 weeks to the long-lived Ames dwarf animal completely reversed the increased life span in these animals. Finally, studies from the Jackson Laboratory comparing over 30 strains of mice indicated that IGF-1 levels at 6 months of age are inversely correlated with life span and that this correlation decreases as animals age. By 18 months of age, the correlation is essentially lost, suggesting that only levels of circulating IGF-1 earlier during the life span are predictive of life span."

    "Based on the literature, GH and IGF-1 have both beneficial and deleterious effects on specific pathologies that undoubtedly influence life span. Therefore, in many cases, the consequences of GH and IGF-1 deficiency are dependent on the species, background strain, and pathologies that the species or strain is susceptible. Those animals that are at risk for cancer, liver, or kidney disease will likely exhibit a shortened life span in response to elevated levels of GH and IGF-1, and we expect that those animals with reduced risk for these diseases will likely not exhibit increased life span in response to this intervention. Similarly, those species at risk for specific cardiovascular diseases (stroke, myocardial infarction, heart failure, vascular cognitive impairment) may benefit from elevated levels of these hormones. These effects are consistent with the classical actions of GH and IGF-1 being important anabolic agents that stimulate cell growth, proliferation, and tissue repair. Because cardiovascular diseases, metabolic diseases, and cancer are all important health issues in the elderly population, the effects of GH/IGF-1 pathway on human health span and life span are predictably complex."



    "Low circulating IGF-I bioactivity is associated with human longevity: Findings in centenarians' offspring"



    "Data on IGF-I system in relation to longevity are still controversial. Bonafè et al. [9] previously found that subjects with at least an A allele of the IGF-I receptor (IGF-IR) gene (G/A, codon 1013) had low levels of free plasma IGF-I and were more represented among long-lived people. In contrast, Paolisso et al. [10] found an increased plasma IGF-I/IGF binding protein 3 (IGFBP-3) molar ratio in healthy centenarians compared to aged subjects. They suggested that this elevated ratio reflected higher IGF-I bioavailability which contributed to the observed improved insulin action in centenarians. An overrepresentation of heterozygous mutations in the IGF-IR gene associated with high serum IGF-I levels and reduced activity of the IGF-IR has been reported in Ashkenazi Jewish centenarians compared to controls [11]. In addition, in humans positive associations between circulating total IGF-I levels and cancer mortality have been found in many studies [12-14], while low total IGF-I levels have been associated with an increased risk for cardiovascular diseases and diabetes [15-22]. On the other hand, Rozing et al. showed that offspring of familial nonagenarians displayed similar IGF-I and IGFBP-3 levels compared to their partners [23].

    These conflicting results probably reflect the complexity of the IGF-system."



    "Functionally significant insulin-like growth factor I receptor mutations in centenarians"




    "Here, we studied the biochemical, phenotypic, and genetic variations in a cohort of Ashkenazi Jewish centenarians, their offspring, and offspring-matched controls and demonstrated a gender-specific increase in serum IGFI associated with a smaller stature in female offspring of centenarians. Sequence analysis of the IGF1 and IGF1 receptor (IGF1R) genes of female centenarians showed overrepresentation of heterozygous mutations in the IGF1R gene among centenarians relative to controls that are associated with high serum IGFI levels and reduced activity of the IGFIR as measured in transformed lymphocytes."



    1. Horm Res. 2004;62 Suppl 1:101-7.


    Insulin-like growth factor I and impaired glucose tolerance.


    Dunger D(1), Yuen K, Ong K.


    Author information:

    (1)University Department of Paediatrics, University of Cambridge, Cambridge, UK.



    The effects of circulating insulin-like growth factor I (IGF-I) on glucose

    metabolism are well recognized. IGF-I is also important in maintaining beta-cell

    mass and regulating endogenous growth hormone (GH) levels. Low IGF-I levels could

    explain links between small birth size and the risk of developing type 2 diabetes

    mellitus in short, obese adults. In a recent prospective study, childhood insulin

    secretion was related to IGF-I levels and statural growth, whereas insulin

    sensitivity was related to early post-natal weight gain. Common genetic

    polymorphisms in the IGF1 gene have been linked to small birth size, post-natal

    growth and future diabetes risk, but these results have been inconsistent. Recent

    adult studies have demonstrated that lower baseline IGF-I levels predict the

    subsequent development of impaired glucose tolerance (IGT), type 2 diabetes and

    cardiovascular disease. Administration of low-dose GH therapy, at a dose that

    minimizes the lipolytic effects of GH and has the ability to increase IGF-I

    levels, enhances insulin sensitivity in young healthy adults and in GH-deficient

    adults and increases insulin secretion in individuals with IGT. Whether the

    administration of low-dose GH, recombinant IGF-I or combined IGF-I/IGF-binding

    protein 3 therapy prevents future development of IGT or type 2 diabetes in

    high-risk normoglycaemic and GH-deficient individuals merits further long-term



    Copyright 2004 S. Karger AG, Basel.


    PMID: 15761241 [PubMed - indexed for MEDLINE]



  18. Dried plums ("prunes") have been shown to increase IGF-1 and this has been suggested as a mechanism underlying the benefits to bone health. I'm not convinced that lower IGF-1 is beneficial for aging and long-term health in humans, in fact I actually believe it may be preferable to maintain higher levels (the pros/cons of IGF-1 might be dependent upon each individual's particular risk factors.) There is substantial evidence of IGF-1 benefiting and protecting bone, brain, muscle and cardiovascular health in humans. However, I know that lower IGF-1 is favored by many CR practitioners and therefore it may be important for them to be aware of this effect of dried plums.

  19. I forgot to add one critical thing: I went off mirtazapine last week (having started tapering ~18 days ago from an already low dose of 7.5 mg.).

    I'd be concerned about mirtazapine, it has shown to be carcinogenic in both mice and rats. I was under the impression that, toxicologically, seeing carcinogenic effects in two species is often considered a potentially serious sign. The fact that both species also developed the same type of cancer and the dose may not have been sufficiently high in mice just adds to that concern. Yet it still obviously got FDA approval... 


    Carcinogenicity studies were conducted with mirtazapine given in the diet at doses of 2, 20, and 200 mg/kg/day to mice and 2, 20, and 60 mg/kg/day to rats. The highest doses used are approximately 20 and 12 times the maximum recommended human dose (MRHD) of 45 mg/day on a mg/m2 basis in mice and rats, respectively. There was an increased incidence of hepatocellular adenoma and carcinoma in male mice at the high dose. In rats, there was an increase in hepatocellular adenoma in females at the mid and high doses and in hepatocellular tumors and thyroid follicular adenoma/cystadenoma and carcinoma in males at the high dose. The data suggest that the above effects could possibly be mediated by non-genotoxic mechanisms, the relevance of which to humans is not known.

    The doses used in the mouse study may not have been high enough to fully characterize the carcinogenic potential of mirtazapine tablets.


  20. Brett: 1) Darkness indicates exposure to oxygen in most varieties of walnuts (including Chandler); 2) shriveledness usually indicates excessive exposure to heat in the drying process; 3) (not obvious from picture, of course) I bit into the one of the left and it tasted rancid.



    You made some other comments about the possible significance and meaning of various aesthetic qualities of walnuts over here too:



    What I'm wondering (and part of the driving reason for my previous post) is: what are you basing this information/interpretation on? And, how confident are you and should we be that this information/interpretation is accurate and/or useful?



    P. S. Brett, any reason why you're quoting full posts? The great thing about switching from the lists is that we can have a "cleaner" text mass.

    Even though it was quoting an entire post it was still a short quote and gave quick and easy context (rather than having to read through the thread, or scroll back up and search etc).

  21. For example, in a lb. bag from Nuts.com, I found several nuts that looked like the one on the left in the attached image (image is of two actual nuts in the bag I recently bought from Nuts.com), and many that were in-between in color and "shriveledness". That's unacceptable. Have you bought walnuts from them recently?


    attachicon.gifNuts.com walnuts.jpg


    But again, it may just be bad luck on my part. But as noted, there were problems with the hazelnuts too. And the raw cashews had small pieces of the shell on some of the nuts (which pieces can in fact contain a non-trivial toxin).




    Edit: higher resolution image attached (the little one shown is a thumbnail you can click on).


    For what reason(s) do you think the walnut on the left is the less desirable of the two?


  22. The Carb-Sane Asylum recently made a blog post titled "The Problem with NHANES Dietary Data" with an interesting table showing NHANES overweight/obesity and dietary data:




    Also, a poster at Carb-Sane Asylum pointed out this:


    1. PLoS One. 2013 Oct 9;8(10):e76632. doi: 10.1371/journal.pone.0076632. eCollection



    Validity of U.S. nutritional surveillance:National Health and Nutrition

    Examination Survey caloric energy intake data, 1971-2010.


    Archer E(1), Hand GA, Blair SN.


    Author information:

    (1)Department of Exercise Science, Arnold School of Public Health, University of

    South Carolina, Columbia, South Carolina, United States of America.


    Comment in

    Adv Nutr. 2015 Mar;6(2):230-3.

    Adv Nutr. 2015 Mar;6(2):229-30.


    IMPORTANCE: Methodological limitations compromise the validity of U.S.

    nutritional surveillance data and the empirical foundation for formulating

    dietary guidelines and public health policies.


    OBJECTIVES: Evaluate the validity of the National Health and Nutrition

    Examination Survey (NHANES) caloric intake data throughout its history, and

    examine trends in the validity of caloric intake estimates as the NHANES dietary

    measurement protocols evolved.


    DESIGN: Validity of data from 28,993 men and 34,369 women, aged 20 to 74 years

    from NHANES I (1971-1974) through NHANES 2009-2010 was assessed by: calculating

    physiologically credible energy intake values as the ratio of reported energy

    intake (rEI) to estimated basal metabolic rate (BMR), and subtracting estimated

    total energy expenditure (TEE) from NHANES rEI to create 'disparity values'.


    MAIN OUTCOME MEASURES: 1) Physiologically credible values expressed as the ratio

    rEI/BMR and 2) disparity values (rEI-TEE).

    RESULTS: The historical rEI/BMR values for men and women were 1.31 and 1.19, (95%

    CI: 1.30-1.32 and 1.18-1.20), respectively. The historical disparity values for

    men and women were -281 and -365 kilocalorie-per-day, (95% CI: -299, -264 and

    -378, -351), respectively. These results are indicative of significant

    under-reporting. The greatest mean disparity values were -716 kcal/day and -856

    kcal/day for obese (i.e., ≥30 kg/m2) men and women, respectively.


    CONCLUSIONS: Across the 39-year history of the NHANES, EI data on the majority of

    respondents (67.3% of women and 58.7% of men) were not physiologically plausible.

    Improvements in measurement protocols after NHANES II led to small decreases in

    underreporting, artifactual increases in rEI, but only trivial increases in

    validity in subsequent surveys. The confluence of these results and other

    methodological limitations suggest that the ability to estimate population trends

    in caloric intake and generate empirically supported public policy relevant to

    diet-health relationships from U.S. nutritional surveillance is extremely



    PMCID: PMC3793920

    PMID: 24130784 [PubMed - indexed for MEDLINE]



  23. Interestingly, in light of the discussion on the Genetics of Obesity thread about whether a tendency towards obesity is a good or bad thing, a follow up analysis by the same authors [2] found that among these mice strains, those that were able to preserve the most fat (due to genetic variations) when subjected to food restriction benefited the most. Those mice that couldn't maintain fat on food restriction, died early(ier). They conclude "[genetic] factors associated with maintaining adiposity are important for survival and life extension under DR."


    If part or all of the benefits of CR seen in rodents are explained by an underlying evolutionary adaption to surviving famine, then a preferential retention of body fat could be an obvious sign that a particular rodent/strain strongly expresses this adaption. Preferential retention of body fat could be suggestive of the organism attempting to store away energy supplies for the future, with the "plan" of sitting out the famine period in a pro-survival("anti-aging") state whilst living off the stored "rations."


    There is of course evidence to suggest however, in humans, that too much body fat, particularly visceral fat, may be detrimental, possibly because it is pro-inflammatory.


    Taken together, I wonder if in humans the much popularly maligned "skinny-fat" body morphology could actually reflect something akin to the successful CR'ed rodents. The skinny-fat combination might ideally reflect a state of lowered caloric intake (skinny) which implies famine, coupled with the pro-survival/anti-aging adaption (fat), along with keeping absolute body fat amounts low enough to avoid the health problems observed in the conventionally overweight/obese.


    It also makes me wonder if womens' tendency toward proportionally higher body fat, as well as live longer, reflects a similar pro-survival evolutionary strategy. Due to the higher and longer-lasting investment requirements for reproduction in females, evolution may have given females similar pro-famine-survival adaptions like preferential fat accumulation and retention.