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Oct 11

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  • Three coffees a day linked to more health than harm: study Thursday November 23rd, 2017

    LONDON (Reuters) – People who drink three to four cups of coffee a day are more likely to see health benefits than harm, experiencing lower risks of premature death and heart disease than those who abstain, scientists said on Wednesday.

    The research, which collated evidence from more than 200 previous studies, also found coffee consumption was linked to lower risks of diabetes, liver disease, dementia and some cancers.

    Three or four cups a day confer the greatest benefit, the scientists said, except for women who are pregnant or who have a higher risk of suffering fractures.

    Coffee is one of the most commonly consumed drinks worldwide. To better understand its effects on health, Robin Poole, a public health specialist at Britain’s University of Southampton, led a research team in an “umbrella review” of 201 studies based on observational research and 17 studies based on clinical trials across all countries and all settings.

    “Umbrella reviews” synthesize previous pooled analyses to give a clearer summary of diverse research on a particular topic.

    “Coffee drinking appears safe within usual patterns of consumption,” Pool’s team concluded in their research, published in the BMJ British medical journal late on Wednesday.

    Drinking coffee was consistently linked with a lower risk of death from all causes and from heart disease. The largest reduction in relative risk of premature death is seen in people consuming three cups a day, compared with non-coffee drinkers.

    Drinking more than three cups a day was not linked to harm, but the beneficial effects were less pronounced.

    Coffee was also associated with a lower risk of several cancers, including prostate, endometrial, skin and liver cancer, as well as type 2 diabetes, gallstones and gout, the researchers said. The greatest benefit was seen for liver conditions such as cirrhosis of the liver.

    Poole’s team noted that because their review included mainly observational data, no firm conclusions could be drawn about cause and effect. But they said their findings support other recent reviews and studies of coffee intake.

    Source: Reuters

  • Mechanism of Chinese Medicine Herbs Effects on Chronic Heart Failure Based on Metabolic Profiling Wednesday November 22nd, 2017

    ORIGINAL: https://doi.org/10.3389/fphar.2017.00864

    • 1School of Preclinical Medicine, Beijing University of Chinese Medicine, Beijing, China

    • 2Beijing University of Chinese Medicine, Dongfang Hospital, Beijing, China

    • 3FengNing Chinese Medicine Hospital, FengNing, China

    Chronic heart failure (CHF) is a major public health problem in huge population worldwide. The detailed understanding of CHF mechanism is still limited. Zheng (syndrome) is the criterion of diagnosis and therapeutic in Traditional Chinese Medicine (TCM). Syndrome prediction may be a better approach for understanding of CHF mechanism basis and its treatment. The authors studied disturbed metabolic biomarkers to construct a predicting mode to assess the diagnostic value of different syndrome of CHF and explore the Chinese herbal medicine (CHM) efficacy on CHF patients. A cohort of 110 patients from 11 independent centers was studied and all patients were divided into 3 groups according to TCM syndrome differentiation: group of Qi deficiency syndrome, group of Qi deficiency and Blood stasis syndrome, and group of Qi deficiency and Blood stasis and Water retention syndrome. Plasma metabolomic profiles were determined by UPLC-TOF/MS and analyzed by multivariate statistics. About 6 representative metabolites were highly possible to be associated with CHF, 4, 7, and 5 metabolites with Qi deficiency syndrome, Qi deficiency and Blood stasis syndrome, and Qi deficiency and Blood stasis and Water retention syndrome (VIP > 1, p < 0.05). The diagnostic model was further constructed based on the metabolites to diagnose other CHF patients with satisfying sensitivity and specificity (sensitivity and specificity are 97.1 and 80.6% for CHF group vs. NH group; 97.1 and 80.0% for QD group vs. NH group; 97.1 and 79.5% for QB group vs. NH group; 97.1 and 88.9% for QBW group vs. NH group), validating the robustness of plasma metabolic profiling to diagnostic strategy. By comparison of the metabolic profiles, 9 biomarkers, 2-arachidonoylglycerophosphocholine, LysoPE 16:0, PS 21:0, LysoPE 20:4, LysoPE 18:0, linoleic acid, LysoPE 18:2, 4-hydroxybenzenesulfonic acid, and LysoPE 22:6, may be especially for the effect of CHM granules. A predicting model was attempted to construct and predict patient based on the related symptoms of CHF and the potential biomarkers regulated by CHM were explored.

    This trial was registered with NCT01939236 (https://clinicaltrials.gov/).

    Introduction

    Chronic heart failure (CHF), as a complex clinical syndrome, results from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood (Hunt et al., 2005). In 2000, an international cooperation research program on cardiovascular disease in Asia (InterASIA) was made, which included 15,518 urban or rural residents from 35 to 74 years old. The results showed that the prevalence of heart failure was 0.9% for the general population, 0.7% for the males, and 1.0% for the females, indicating that there were ~4 million heart failure targets in China (Gu et al., 2003). CHF is the only cardiovascular disease with an increasing hospitalization burden and an ongoing drain on health care expenditures, for its complex molecular mechanisms cannot be easily deciphered (Ramani et al., 2010). As a complementary alternative, Traditional Chinese Medicine (TCM) may be to improve the state of CHF. Zheng (syndrome) is the key pathological principle of TCM. All diagnostic and therapeutic methods in TCM are based on the differentiations of syndrome, and this concept has been used for thousands of years in China (Gu, 1956; Li et al., 2007). Syndrome differentiation was based on information from traditional four diagnostic methods. For the complexity and multilevel relationships of four diagnostic methods, a mode which could distinguish syndrome differentiation and be verified is imperative. Many techniques of data mining are applied to syndromes in TCM (Lukman et al., 2007; Shi and Zhou, 2007; Gao et al., 2010; Yao et al., 2011). Chen et al. proposed a discovery algorithm based on revised mutual information to discover syndromes for chronic renal failure (Chen et al., 2007). In regards to coronary artery disease, Liu et al. designed standardization scale on inquiry diagnosis and constructed this diagnostic model by using the method of multi-label learning (Liu et al., 2010). With many achievements have been made in syndrome differentiation, there are still some problems left, deserving further discussion (Wang et al., 2009; Lu et al., 2012). Syndromes-identified techniques such as multi-label learning could identify syndrome information in TCM more effectively, and solve the multi-label problems of one sample with several syndromes. While there are many research challenges of multi-label learning to be addressed in the future, such as multi-label data usually suffers from inherent class imbalance and unequal misclassification costs. Metabolomics is distinctive for its overall concept and dynamic character, which may be an effective tool to reveal the scientific connotation of TCM. Metabolic alterations are measured in response to disease progression (Cheng et al., 2015). LC-MS based methods provide more compatible technique and high quality data for sensitive detection of small-molecule metabolites with robust reliability and reproducibility (Gika et al., 2007). Abnormal metabolism may characterize syndrome differentiation. Our previous metabolomics study on blood stasis syndrome of CHF showed glucose metabolism and lipid metabolism disorders reinforce each other, which results a deterioration of coronary artery disease with blood stasis syndrome. These metabolites maybe used as indicators of clinical diagnosis and treatment of coronary artery disease (Wang et al., 2011). Wang et al. concluded that NMR-based metabolomics approach demonstrated alteration of energy metabolism and other potential biological mechanisms underlying CHF (Wang et al., 2013b). In this paper, we try to discover comprehensive metabolomic characteristics of CHF and its syndrome differentiation for accurate clinical diagnosis. A syndrome predictive method for CHF was to build with non-targeted metabolomics and potential biomarkers related to CHF syndrome differentiation were to explore. The predictive performance would be validated and these potential biomarkers would be used as predictors to diagnose the patients. Besides, special metabolic characteristic of CMH on CHF would also be elaborated.

    Materials and Methods

    Patients and Study Design

    The study included 110 patients with chronic heart failure from 11 hospitals (The Second Affiliated Hospital of Beijing University of Chinese Medicine, Zhengzhou Hospital of TCM in Henan Province, The Affiliated Hospital to Changchun University of CM, Guang’anmen Hospital which was Affiliated to China Academy of Chinese Medicine Sciences, Hubei Provincial Hospital of TCM, Wuhan Hospital of TCM, Hospital of T.C.M.S Shijingshan District, Beijing Changping Hospital, Hospital of T.C.M.S Beijing Miyun County, Beijing Changping Hospital of Integrated Chinese and Western Medicine, TCM Hospital of Beijing Huairou and TCM Hospital of Tongzhou District) in China between May 2010 and December 2014. During the same period, 54 normal healthy participants of matched age were included from medical center of Dongzhimen Hospital as controls.

    Diagnostic Criteria

    Diagnostic criteria of CHF: 2007 China Guideline for the Diagnosis and Treatment of CHF (Chinese Society of Cardiology of Chinese Medical Association and Editorial Board of Chinese Journal of Cardiology, 2007). Heart function standard: The Criteria for Diagnosis and Treatment of Heart Disease first published by the New York Heart Association (NYHA) (Feinstein, 1964). Syndrome differentiation of CHF patients followed the TCM differentiation standard: according to the Guiding Principles for the Clinical Study of New Drugs in Traditional Chinese Medicine released in 2002 (Zheng, 2002).

    Inclusion Criteria

    Primary heart disease in this research was Coronary Heart Disease (CHD), which could be diagnosed by coronary computed tomography, coronary angiography, limb-salvage Q wave for electrocardiogram (ECG), history of acute myocardial infarction, ECG test, radionuclide examination support, etc. The included patients also had no history of taking antihypertensive drugs and exhibited a blood pressure under 160/100 mmHg or of hypertension. Following symptoms and signs were observed with a history of CHD: fatigue, difficulty breathing, fluid retention (edema), left ventricular enlargement, NYHA functional classification II or III, and end systolic volume of left ventricular increase and left ventricular ejection fraction (LVEF)<40. All subjects between 40 and 75 years old; If there was a “No” answer for any issue, the subject could not enter into this research.

    Exclusion Criteria

    Patients with one of the following diseases were excluded: (1) serious valvular heart disease; (2) cardiomyopathy; (3) pericardial disease; (4) congenital heart disease; (5) cardiac shock; (6) acute myocardial infarction (AMI) within 4 weeks; (7) acute myocarditis or serious arrhythmia with variation in hemodynamics. Patients who suffer from pulmonary artery hypertension caused by cor pulmonale, pulmonary embolism, or stroke within a half year were also excluded. Patients who suffer from serious hepatic or renal deficiency. Patients who suffer from diseases of blood system or malignant tumor. Patients who suffer from diabetes mellitus with serious complications, hyperthyrea, or hypothyrea. Patients who suffer from infection. Pregnant women or women in lactation. Patients with mental disorders. Patients with infectious disease or who join in other trials within 2 months of the present study.

    All qualified participants had signed informed consent prior to the enrollment. This study was conducted according to the principles of the Declaration of Helsinki and the principles of Good Clinical Practice.

    All patients formed the chronic heart failure group, and were further divided into 3 groups according to TCM syndrome differentiation, including group of Qi deficiency syndrome (QD), group of Qi deficiency and Blood stasis syndrome (QB), and group of Qi deficiency and Blood stasis and Water retention syndrome (QBW). The normal healthy participants composed the NH group.

    Besides, according to previous research (Wang et al., 2013a), the most syndrome of CHF was Qi deficiency and Blood stasis syndrome, so 64 of the participants with CHF of Qi deficiency and Blood stasis syndrome (QB group) were enrolled in a randomized double-blind controlled clinical trial. According to the 2007 China Guidelines for the Diagnosis and Treatment of Chronic Heart Failure (Chinese Society of Cardiology of Chinese Medical Association and Editorial Board of Chinese Journal of Cardiology, 2007), all patients in the two groups received the standardized western medicine treatment, which includes angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs), b-blockers, and diuretics. Except the standardized western medicine treatment, subjects with the CHM treatment were defined as the CHM group, and subjects with the placebo intervention were defined as the placebo group. The subjects were treated with CHM granules, made from Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao (huangqi, 60 g), Codonopsis pilosula (Franch.) Nannf (dangshen, 15 g), Salvia miltiorrhiza Bge (danshen 15 g), Paeonia lactiflora Pall (chishao, 15 g), Prunus davidiana (Carr.) Franch. (taoren, 10 g), and Carthamus tinctorius L. (honghua, 10 g) or placebo granules twice per day for 4 weeks. The CHM granules and placebo granules were offered by Beijing Kang Rentang pharmaceutical industry (Beijing, China). Finally, 31 patients were in CHM group, and 33 were in placebo group.

    Plasma samples were collected on morning of the first and the twenty-eighth day after enrollment and were immediately frozen at −80°C. Six minutes of walking test (6 MWT) and echocardiography were also detected at the same time. Both the observer of the 6 MWT and the echo technician were blind to the allocation of the patients.

    After several preliminary experiments by different mixtures of methanol, acetonitrile, and methanol/acetonitrile (1:1), finally the extraction solvent was acetonitrile. By mixing equal amounts of plasma (30 μL) from all samples, pooled quality control samples were prepared to ensure data quality for metabolic profiling. Detailed sample methods were shown in the Supplementary Material.

    This research was approved by the Institutional Committee on Human Research of Beijing University of Chinese Medicine (No. 200807007), and this trial is registered with NCT01939236 (Luo et al., 2015).

    Ultra Performance Liquid Chromatography/Time of Flight Mass Spectrometry (UPLC-TOF MS) Metabolomics Study Analysis

    The liquid chromatographic separation of processed plasma was conducted on a 100*2.1-mm ACQUITY UPLC ° R BEH C18 1.7-um column (Lot No. 0252350221) using an ACQUITY Ultra Performance LC (Waters Corporation, Milford Massachusetts, USA), whereas mass spectrometry was performed on a SYNAPT G2 Quadrupole-Time of Flight system (Waters Corporation, Milford Massachusetts, USA). With a random-number generator in Excel (Microsoft, Redmond, Washington), 3 sequences for samples in discovery phase, validation phase and placebo group were assigned by the study administrator. During analyses of the sample sequence, after each 20 injections, then 1 quality control sample was run to check the stability of system. The acquired mass spectrometry data were exported to data format (.centroid) files by Masslynx Software (version 4.0, Waters Corporation). Data pre-treatment procedures, such as nonlinear retention time alignment, peak discrimination, filtering, alignment, matching, and identification, were performed in Progenesis QI (34 Maple Street, Milford Massachusetts, 01757, USA), and retention time and the mass-to ratio data pairs as the parameters for each ion. The UPLC-QTOF-MS characteristic chromatogram of CHM granules (6 herbs) was identified, and detailed method was shown in the Supplementary Material. Disturbed metabolites and metabolic pathways were identified by open database sources, including Human Metabolome Database (http://www.hmdb.ca/), METLIN (https://metlin.scripps.edu/), KEGG (http://www.genome.jp/kegg/pathway.html), and MetaboAnalyst (http://www.metaboanalyst.ca/faces/home.xhtml)…

    Source: Frontiers

  • The sugar industry blocked research linking sucrose to heart disease and cancer from publication 50 YEARS ago, damning report reveals Wednesday November 22nd, 2017

    The researchers at the University of California at San Francisco have uncovered data showing the sugar industry hid research linking sugar to cancer in 1968

    New documents show the Sugar Association funded an animal experiment called Project 259 to evaluate sucrose’s effects on cardiovascular health
    But when the data showed a clear link between sucrose and poor heart health, they pulled the plug

    The researchers say that, had this paper been published in 1968, it would have led to scrutiny and even regulation of sugar by the FDA

    The sugar industry blocked the release of a study showing sucrose directly increases the risk of heart disease and cancer in 1968, newly-uncovered documents reveal.

    The research, which was funded and designed by the sugar industry, was intended to dispel fears that fructose-containing sugars affect blood lipids.

    But internal correspondence uncovered by researchers at the University of California at San Francisco, show that industry leaders pulled the plug on its publication after getting wind that it would prove the clearest link between sugar and disease ever found.

    The finding, published today in PLOS Biology, is the latest in a series of bombshell reports from investigative researcher Dr Cristin Kearns and co-author Dr Stanton Glantz, who was the first researcher to reveal Big Tobacco was hiding research on the danger of cigarettes in 1996.

    Last year the duo sent shockwaves through the nutrition world with a study that showed the sugar industry had paid Harvard University’s most respected nutrition scientist to play down the health dangers of sugar, and demonize fats.

    Speaking to Daily Mail Online, they say that, had this new study been published in 1968 as planned, it would have automatically triggered a review of sucrose by the US Food and Drug Administration, which would have likely led to regulation of sugar.

    Instead, they say, it has taken five decades for the scientific community to reach relative agreement that sugar is bad for you, and has a direct link to cancer and heart disease.

    ‘The sugar industry has been playing the same games as Big Tobacco to protect their financial interests,’ Dr Glantz told Daily Mail Online.

    ‘The more we look, the more we see that the sugar industry has had a sophisticated understanding of science for decades, sophisticated enough to manipulate it.

    ‘This study, if it had been published, would have been quite cutting edge for its time. Had that work moved forward, it would’ve advanced the triglycerides-sugar debate forward by decades.

    ‘That’s why they killed it.’

    Today’s paper – the third collaboration between Glantz and Cearns, and the fourth on this subject for Cearns, a dentist-turned-investigator – is based on a review of archived industry documents.

    It reveals the Sugar Research Foundation (SRF), now known as the Sugar Association, funded an animal experiment called Project 259 to evaluate sucrose’s effects on cardiovascular health.

    The sugar industry has had a sophisticated understanding of science for decades, sophisticated enough to manipulate it Co-author Dr Stanton Glantz

    But, as with many research papers, it got delayed. The researcher, excited by his findings, went to the SRF asking for another boost in funding to take his work further.

    Reviewing the data, which indicated an association with heart disease and bladder cancer, the SRF pulled the plug on the entire project.

    Dr Cearns explains that this study would have triggered scrutiny or regulation of sucrose.

    At the time, the FDA was operating under something called the Delaney clause, which made is compulsory to scrutinize or regulate anything that was found to have a cancerous link based on an animal study.

    In fact, a year before, the SRF had criticized animal studies. For unknown reasons, the foundation went on to fund its own animal study – but shut it down when they heard the damning findings.

    Even today, the Sugar Association denies that sugar has any direct detrimental health impacts beyond weight gain.

    Last year the Sugar Association criticized a mouse study suggesting a link between sugar and the growth and spread of tumors.

    They said ‘no credible link between ingested sugars and cancer has been established.’

    The analysis of the industry’s own documents, in contrast, suggests the industry knew of animal research indicating this link, and halted funding to protect its commercial interests half a century ago.

    Dr Kearns said she knows of at least 300 industry-funded studies between 1943 and 1972.

    ‘There is more material than I have the ability to write about,’ she told Daily Mail Online.

    ‘We will need far more investigators to uncover all of this.’

    WHAT WE NOW KNOW ABOUT SUGAR’S LINK TO THE HEART

    Today, we are urged to limit our sugar intake as much as possible.

    According to FDA regulations, women should have no more than 25g (six teaspoons) of added sugar per day.

    That is less than a can of Coca Cola.

    Men should have no more than 36g (nine teaspoons) extra.

    That equates to a regular Snickers bar.

    Sugar, peer-reviewed studies now show, triggers insulin resistance, lower good cholesterol and dangerous bad cholesterol.

    It also causes inflammation of the arteries.

    These are all direct causes of heart disease.

    Dr Glantz concurs.

    He was the first to concretely highlight tobacco’s direct links to disease, after receiving more than 4,000 pages of internal Big Tobacco documents in 1994 from an anonymous source. The documents unveiled decades of manipulated research and hidden data proving that cigarettes cause disease.

    Dr Glantz went on to publish a book called The Cigarette Papers, which paved the way to more than 1,000 research papers on cigarettes and disease.

    Now, he says, we are seeing the same with sugar.

    ‘The kind of manipulation of research is similar what the tobacco industry does,’ he claims.

    ‘This kind of behavior calls into question sugar industry funded studies as a reliable source of information for public policy making.’

    His previous analysis with Dr Kearns found the SRF had secretly funded a 1967 review playing down evidence linking sucrose consumption to coronary heart disease.

    That noted gut microbes may explain why rats fed sugar had higher levels of cholesterol than those fed starch, but dismissed the relevance of animal studies to understanding human disease.

    The foundation launched its coronary heart disease research in 1965. The first project was the review published in the New England Journal of Medicine in 1967.

    It focused on fat and cholesterol as the dietary cause of coronary heart disease, while downplaying sugar consumption as a risk factor.

    Worrying facts: Do you know how much sugar is in your food?

    In the new paper the team reports the following year SRF, which changed its name in 1968 to ISRF (International Sugar Research Foundation) launched a rat study called Project 259.

    It was to ‘measure the nutritional effects of the (bacterial) organisms in the intestinal tract’ when sucrose was consumed, compared to starch.

    The research by W.R.F. Pover of the University of Birmingham, in England, suggested gut bacteria help control sugar’s adverse cardiovascular effects.

    Pover also reported findings that might indicate an increased risk of bladder cancer.

    Dr Kearns said: ‘This incidental finding of Project 259 demonstrated to ISRF that sucrose vs. starch consumption caused different metabolic effects, and suggested that sucrose, by stimulating urinary beta-glucuronidase, may have a role in the pathogenesis (cause) of bladder cancer.’

    The ISRF described the finding in a September 1969 internal document as ‘one of the first demonstrations of a biological difference between sucrose and starch fed rats.’

    But soon after ISRF learned about these results – and shortly before the research project was complete – the group terminated funding for the project, and no findings from the work were published.

    In the 1960s, scientists disagreed over whether sugar could raise other harmful blood fats called triglycerides more than starch, and Project 259 would have bolstered the case that it could, the researchers argue.

    What is more, terminating Project 259 echoed SRF’s earlier efforts to downplay sugar’s role in cardiovascular disease.

    Dr Glantz added: ‘Our study contributes to a wider body of literature documenting industry manipulation of science.

    ‘Based on ISRF’s interpretation of preliminary results, extending Project 259’s funding would have been unfavourable to the sugar industry’s commercial interests.’

    Funding was cut off before that could happen.

    LAST YEAR’S REPORT: HOW THE SUGAR INDUSTRY FUNDED RESEARCH TO DEMONIZE FAT

    The sugar industry paid prestigious Harvard scientists to publish research saying fat – not sugar – was a key cause of heart disease, newly unveiled documents reveal.

    At the time, in the 1960s, conflict of interest disclosure was not required.

    It meant sugar chiefs could work closely with researchers to re-draft and re-draft their paper until it was ‘satisfactory’ – without having to report their involvement.

    The result shaped public health approaches to nutrition for years.

    The findings, revealed today in a special report in JAMA Internal Medicine, has sent shockwaves through the research community.

    Source: Daily Mail

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