Ram B. Singh

Dietary intake, plasma levels of antioxidant vitamins, and oxidative stress in relation to coronary artery disease in elderly subjects.

The prevalence of coronary artery disease (CAD) in the urban population of India is similar to that in developed countries; Indian immigrants in industrialized countries have the highest prevalence of CAD. This is a cross-sectional survey within a random sample of a single urban setting in India. The relation between risk of CAD and plasma levels of vitamins A, C, E, and beta-carotene was examined in 72 of 595 elderly subjects (12.1%) with CAD (aged 50 to 84 years). Plasma levels of vitamins A, C, E, and beta-carotene were significantly related to risk of CAD. Smoking (n = 145) and diabetes (n = 70) were the confounding factors. Lipid peroxides were higher in patients with CAD and diabetes, and in those who smoked. The inverse relation between CAD and low plasma vitamin C was substantially reduced after adjustment for smoking and diabetes. Vitamin A and E levels remained independently and inversely related to the risk of CAD after adjustment for age, smoking, diabetes, blood pressure, blood lipoproteins, and relative weight and body mass index. The adjusted odds ratios for CAD between the lowest and highest quintiles of vitamin E levels were 2.53 (95% confidence interval [CI] 1.11 to 5.31), vitamin C, 2.21 (95% CI 1.12 to 3.15), and beta-carotene, 1.72 (95% CI 0.88 to 3.62). The fatty acid composition of the diet, blood lipid levels, central obesity (waist-hip ratio), smoking habits, blood pressure, and plasma insulin levels do not appear to account for high rates of CAD among elderly Indians.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidemiologic study of diet and coronary risk factors in relation to central obesity and insulin levels in rural and urban populations of North India

In a population survey of 162 rural and 152 urban subjects aged 26-65 years at Moradabad, the findings are compared with existing data on Indian immigrants to Britain and United States. In comparison with rural subjects, urban subjects had a higher prevalence of coronary artery disease (8.6 vs. 3.0%) and diabetes (7.9 vs 2.5%), higher blood pressures, total and low density lipoprotein cholesterol, triglycerides and postprandial 2-h blood glucose and plasma insulin similar to observations made in UK in immigrants compared to Europeans. Fasting plasma insulin and high density lipoprotein cholesterol levels in urban subjects were comparable with rural subjects. Mean body weights were significantly higher in urban women, but not in men, than in rural subjects. However the body mass index (22.9 +/- 4.2 vs. 21.6 +/- 2.4 kg/m2) and waist-hip girth ratio (0.89 +/- 0.10 vs. 0.86 +/- 0.07) were significantly higher in urban men compared to rural men without such differences in women. Underlying these differences in risk factors, urban subjects had three times better socioeconomic status than rural subjects and were eating higher total and saturated fat, cholesterol and refined carbohydrates and lower total and complex carbohydrates compared to rural men and women. Energy expenditure during routine and spare time physical activity was significantly higher in rural compared to urban subjects. Those patients who had risk factors, showed lesser physical activity and had greater adverse factors in the diet compared to subjects without risk factors. Body mass index and waist-hip girth ratio in patients with risk factors were significantly higher than in subjects without risk factors. The findings suggest that decreased consumption of total and saturated fat and increased physical activity may be useful for prevention of coronary artery disease among urbans as well as in immigrants.

Circadian heart rate and blood pressure variability considered for research and patient care

OBJECTIVESnTo review mechanisms of circadian variations in heart rate variability (HRV) and blood pressure variability (BPV) and mortality and morbidity due to cardiovascular diseases (CVD).nnnMETHODSnResults from 7-day/24-h HRV and BPV are interpreted by gender and age-specified reference values in the context of a Medline search.nnnRESULTSnAbnormal HRV and BPV measured around the clock for 7 days provides information on the risk of subsequent morbid events in subjects without obvious heart disease and without abnormality outside the conventional (in the sense of chronobiologically unquantified) physiological range. Meditation, beta-blockers, ACE inhibitors, n-3 fatty acids and estrogens may have a beneficial influence on HRV, but there is no definitive outcome-validated therapy. Low HRV has been associated with a risk of arrhythmias and arrhythmic death, unstable angina, myocardial infarction, progression of heart failure and atherosclerosis. BPV may be characterized by treatable circadian-hyper-amplitude-tension (CHAT), which can be transient 24-h CHAT or 7-day-CHAT, MESOR-hypertension and/or an unusually-timed (odd) circadian acrophase (ecphasia), all associated with an increased risk of stroke, stroke death, myocardial infarction, and kidney disease.nnnCONCLUSIONSnPrecise insight into the patho-physiology in time of HRV and BPV is needed with development of a consensus on best measures of HRV for clinical purposes and to determine when a 7-day record interpreted chronobiologically suffices and when it does not, for detection within as well as outside the conventional normal range, for diagnostic clinical practice and to direct therapy of risk greater than that associated with hypertension, smoking or any other risk factor.

Diet, central obesity and prevalence of hypertension in the urban population of South India

Central obesity is a strong predictor of higher prevalence of diabetes, hypertension and coronary artery disease among Indian immigrants to Britain. To test this hypothesis in Indians, 1569 adults, between 25 and 64 years of age, from 750 randomly selected households (representative of 0.52 million population of Trivandrum city, Kerala) were selected for this study. The response rate was roughly 95% and the sample consisted of 1497 individuals (737 males and 760 females). The survey methods included dietary diaries for 7-day food intake record, blood pressure measurements using a mercury sphygmo-manometer and anthropometric measurements. The prevalence rates of hypertension between 25 and 64 years was 189/1000 (95% confidence limits 85-360) and between 45 and 64 years was 335/1000 (95% confidence limits 210-460) which is higher than in Western populations. The prevalence was higher in males than females in the younger age groups and comparable in both sexes in the upper age groups. The prevalence of central obesity was significantly higher among male (77.2 vs. 48.9%) and female (84.0 vs. 51.4%) hypertensives compared to non-hypertensive subjects; however, mean body weight, body mass index and waist-hip ratio (WHR) were lower among Indian men compared to a British comparison group. Thus, comparison of Indian men with Britons showed that obesity, salt and alcohol intake, sedentariness, smoking and dietary fat intake do not explain the cause of higher prevalence of hypertension among South Indian men from Kerala.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Antioxidant-Rich Foods on Plasma Ascorbic Acid, Cardiac Enzyme, and Lipid Peroxide Levels in Patients Hospitalized with Acute Myocardial Infarction

OBJECTIVEnTo determine whether a fat- and energy-reduced diet rich in antioxidant vitamins C and E, beta carotene, and soluble dietary fiber reduces free-radical stress and cardiac enzyme level and increases plasma ascorbic acid level 1 week after acute myocardial infarction.nnnDESIGNnRandomized, single blind, controlled study.nnnSETTINGnPrimary- and secondary-care research center for patients with myocardial infarction.nnnSUBJECTSnAll subjects with suspected acute myocardial infarction (n = 505) were considered for entry to the study. Subjects with definite or possible acute myocardial infarction and unstable angina (according to World Health Organization criteria) were assigned to either an intervention diet (n = 204) or a control diet (n = 202) within 48 hours of symptoms of infarction.nnnINTERVENTIONSnIntervention and control groups were advised to consume a fat-reduced, oil-substituted diet. The intervention group was also advised to eat more fruits, vegetable soup, pulses, and crushed almonds and walnuts mixed with skim milk.nnnMAIN OUTCOME MEASURESnReduction in plasma lipid peroxide and lactate dehydrogenase cardiac enzyme levels, increase in plasma ascorbic acid level, and compliance with diet, especially with vitamin C intake as determined by chemical analysis.nnnSTATISTICAL ANALYSISnA two-sample t test using one-way analysis of variance for comparison of data.nnnRESULTSnPlasma lipid peroxide level decreased significantly in the intervention group compared with the control group (0.59 pmol/L in the intervention group and 0.10 pmol/L in the control group; 95% confidence interval of difference = 0.19 to 0.83). Lactate dehydrogenase level increased less in the intervention group than in the control group (427.7 vs 561.2 U/L; confidence interval of difference = 82.9 to 184.7). Plasma ascorbic acid level increased more in the intervention group than in the control group (23.38 vs 7.95 mumol/L; confidence interval of difference = 12.85 to 26.13).nnnAPPLICATIONS/CONCLUSIONSnConsumption of an antioxidant-rich diet may reduce the plasma levels of lipid peroxide and cardiac enzyme and increase the plasma level of ascorbic acid. Antioxidant-rich foods may reduce myocardial necrosis and reperfusion injury induced by oxygen free radicals.

Chronoastrobiology: proposal, nine conferences, heliogeomagnetics, transyears, near-weeks, near-decades, phylogenetic and ontogenetic memories.

Chronoastrobiology: are we at the threshold of a new science? Is there a critical mass for scientific research? A simple photograph of the planet earth from outer space was one of the greatest contributions of space exploration. It drove home in a glance that human survival depends upon the wobbly dynamics in a thin and fragile skin of water and gas that covers a small globe in a mostly cold and vast universe. This image raised the stakes in understanding our place in that universe, in finding out where we came from and in choosing a path for survival. Since that landmark photograph was taken, new astronomical and biomedical information and growing computer power have been revealing that organic life, including human life, is and has been connected to invisible (non-photic) forces, in that vast universe in some surprising ways. Every cell in our body is bathed in an external and internal environment of fluctuating magnetism. It is becoming clear that the fluctuations are primarily caused by an intimate and systematic interplay between forces within the bowels of the earth--which the great physician and father of magnetism William Gilbert called a small magnet--and the thermonuclear turbulence within the sun, an enormously larger magnet than the earth, acting upon organisms, which are minuscule magnets. It follows and is also increasingly apparent that these external fluctuations in magnetic fields can affect virtually every circuit in the biological machinery to a lesser or greater degree, depending both on the particular biological system and on the particular properties of the magnetic fluctuations. The development of high technology instruments and computer power, already used to visualize the human heart and brain, is furthermore making it obvious that there is a statistically predictable time structure to the fluctuations in the suns thermonuclear turbulence and thus to its magnetic interactions with the earths own magnetic field and hence a time structure to the magnetic fields in organisms. Likewise in humans, and in at least those other species that have been studied, computer power has enabled us to discover statistically defined endogenous physiological rhythms and further direct effects that are associated with these invisible geo- and heliomagnetic cycles. Thus, what once might have been dismissed as noise in both magnetic and physiological data does in fact have structure. And we may be at the threshold of understanding the biological and medical meaning and consequences of these patterns and biological-astronomical linkages as well. Structures in time are called chronomes; their mapping in us and around us is called chronomics. The scientific study of chronomes is chronobiology. And the scientific study of all aspects of biology related to the cosmos has been called astrobiology. Hence we may dub the new study of time structures in biology with regard to influences from cosmo- helio- and geomagnetic rhythms chronoastrobiology. It has, of course, been understood for centuries that the movements of the earth in relation to the sun produce seasonal and daily cycles in light energy and that these have had profound effects on the evolution of life. It is now emerging that rhythmic events generated from within the sun itself, as a large turbulent magnet in its own right, can have direct effects upon life on earth. Moreover, comparative studies of diverse species indicate that there have also been ancient evolutionary effects shaping the endogenous chronomic physiological characteristics of life. Thus the rhythms of the sun can affect us not only directly, but also indirectly through the chronomic patterns that solar magnetic rhythms have created within our physiology in the remote past. For example, we can document the direct exogenous effects of given specific solar wind events upon human blood pressure and heart rate. We also have evidence of endogenous internal rhythms in blood pressure and heart rate that are close to but not identical to the period length of rhythms in the solar wind. These were installed genetically by natural selection at some time in the distant geological past. This interpretive model of the data makes the prediction that the internal and external influences on heart rate and blood pressure can reinforce or cancel each other out at different times. A study of extensive clinical and physiological data shows that the interpretive model is robust and that internal and external effects are indeed augmentative at a statistically significant level. Chronoastrobiological studies are contributing to basic science--that is, our understanding is being expanded as we recognize heretofore unelaborated linkages of life to the complex dynamics of the sun, and even to heretofore unelaborated evolutionary phenomena. Once, one might have thought of solar storms as mere transient perturbations to biology, with no lasting importance. Now we are on the brink of understanding that solar turbulences have played a role in shaping endogenous physiological chronomes. There is even documentation for correlations between solar magnetic cycles and psychological swings, eras of belligerence and of certain expressions of sacred or religious feelings. Chronoastrobiology can surely contribute to practical applications as well as to basic science. It can help develop refinements in our ability to live safely in outer space, where for example at the distance of the moon the magnetic influences of the sun will have an effect upon humans unshielded by the earths native magnetic field. We should be better able to understand these influences as physiological and mechanical challenges, and to improve our estimations of the effects of exposure. Chronoastrobiology moreover holds great promise in broadening our perspectives and powers in medicine and public health right here upon the surface of the earth. Even the potential relevance of chronoastrobiology for practical environmental and agricultural challenges cannot be ruled out at this early stage in our understanding of the apparently ubiquitous effects of magnetism and hence perhaps of solar magnetism on life. The evidence already mentioned that fluctuations in solar magnetism can influence gross clinical phenomena such as rates of strokes and heart attacks, and related cardiovascular variables such as blood pressure and heart rate, should illustrate the point that the door is open to broad studies of clinical implications. The medical value of better understanding magnetic fluctuations as sources of variability in human physiology falls into several categories: 1) The design of improved analytical and experimental controls in medical research. Epidemiological analyses require that the multiple sources causing variability in physiological functions and clinical phenomena be identified and understood as thoroughly as possible, in order to estimate systematic alterations of any one variable. 2) Preventive medicine and the individual patientscare. There are no flat baselines, only reference chronomes. Magnetic fluctuations can be shown statistically to exacerbate health problems in some cases. The next step should be to determine whether vulnerable individuals can be identified by individual monitoring. Such vulnerable patients may then discover that they have the option to avoid circumstances associated with anxiety during solar storms, and/or pay special attention to their medication or other treatments. Prehabilitation by self-help can hopefully complement and eventually replace much costly rehabilitation. 3) Basic understanding of human physiological mechanisms. The chronomic organization of physiology implies a much more subtle dynamic integration of functions than is generally appreciated. All three categories of medical value in turn pertain to the challenges for space science of exploring and colonizing the solar system. The earths native magnetic field acts like an enormous umbrella that offers considerable protection on the surface from harsh solar winds of charged particles and magnetic fluxes. The umbrella becomes weaker with distance from the earth and will offer little protection for humans, other animals, and plants in colonies on the surface of the moon or beyond. Thus it is important before more distant colonization is planned or implemented to better understand those magnetism-related biological- solar interactions that now can be studied conveniently on earth. (ABSTRACT TRUNCATED)

100 or 30 Years after Janeway or Bartter, Healthwatch helps avoid 'flying blind'

Longitudinal records of blood pressure (BP) and heart rate (HR) around the clock for days, weeks, months, years, and even decades obtained by manual self-measurements (during waking) and/or automatically by ambulatory monitoring reveal, in addition to well-known large within-day variation, also considerable day-to-day variability in most people, whether normotensive or hypertensive. As a first step, the circadian rhythm is considered along with gender differences and changes as a function of age to derive time-specified reference values (chronodesms), while reference values accumulate to also account for the circaseptan variation. Chronodesms serve for the interpretation of single measurements and of circadian and other rhythm parameters. Refined diagnoses can thus be obtained, namely MESOR-hypertension when the chronome-adjusted mean value (MESOR) of BP is above the upper limit of acceptability, excessive pulse pressure (EPP) when the difference in MESOR between the systolic (S) and diastolic (D) BP is too large, CHAT (circadian hyper-amplitude tension) when the circadian BP amplitude is excessive, DHRV (decreased heart rate variability) when the standard deviation (SD) of HR is below the acceptable range, and/or ecphasia when the overall high values recurring each day occur at an odd time (a condition also contributing to the risk associated with non-dipping). A non-parametric approach consisting of a computer comparison of the subjects profile with the time-varying limits of acceptability further serves as a guide to optimize the efficacy of any needed treatment by timing its administration (chronotherapy) and selecting a treatment schedule best suited to normalize abnormal patterns in BP and/or HR. The merit of the proposed chronobiological approach to BP screening, diagnosis and therapy (chronotheranostics) is assessed in the light of outcome studies. Elevated risk associated with abnormal patterns of BP and/or HR variability, even when most if not all measurements lie within the range of acceptable values, becomes amenable to treatment as a critical step toward prevention (prehabilitation) to reduce the need for rehabilitation (the latter often after costly surgical intervention).

Fatty acids in the causation and therapy of metabolic syndrome.

The role of fatty acids in the prevention and pathogenesis of metabolic syndrome leading to cardiovascular diseases, type 2 diabetes and insulin resistance are reviewed. We did Medline, PubMed search till March, 2007. Excess of linoleic acid, trans fatty acids (TFA), saturated and total fat as well as refined starches and sugar are proinflammatory. Low dietary monounsaturated fatty acids (MUFA) and n-3 fatty acids and other long chain polyunsaturated fatty acids (LCPUFA) are important in the pathogenesis of metabolic syndrome. Sedentary behaviour in conjunction with mental stress and various personality traits can enhance sympathetic activity and increase the secretion of catecholamine, cortisol and serotonin that appear to be underlying mechanisms of obesity and metabolic syndrome. Excess secretion of these neurotransmitters in conjunction of underlying long chain PUFA deficiency, and excess of proinflammatory nutrients, may damage the neurons via proinflammatory cytokines, in the ventromedial hypothalamus and insulin receptors in the brain, especially during fetal life, infancy and childhood, resulting into their dysfunction. Since 30–50% of the fatty acids in the brain are LCPUFA, especially omega-3 fatty acids, which are incorporated in the cell membrane phospholipids, it is possible that their supplementation may be protective. Omega-3 fatty acids are also known to enhance parasympathetic activity and increase the secretion of anti-inflammatory cytokines IL-4 and IL-10, as well as acetylecholine in the hippocampus. It is possible that marginal deficiency of LCPUFA, especially n-3 fatty acids, due to poor dietary intake during the critical period of brain growth and development in the fetus and infant, and also possibly in the child, adolescents and adults, may enhance oxidative stress and the release of proinflammatory cytokines; tumor necrosis factor-alpha, interleukin-1, 2 and 6 and cause neuronal and beta-cell dysfunction. Experimental studies indicate that ventromedial hypothalamic lesion in rats induces hyperphagia, resulting in glucose intolerance and insulin resistance. Administration of neuropeptide Y abolished the hyperphagia and ob mRNA (leptin mRNA) in these rats. Treatment with diets rich in MUFA and omega-3 fatty acids, meditation, beta blockers, ACE inhibitors, and phytochemicals may have a beneficial influence on insulin receptors and ventromedial hypothalamic dysfunction, causing beneficial effects in metabolic syndrome. Despite weaknesses, epidemiological studies and intervention trials indicate that treatment with n-3 fatty acids and MUFA rich foods may be applied to clinical practice and used to direct therapy for prevention of metabolic syndrome. Intervention trials with Columbus diet and lifestyle in patients with metabolic syndrome would be necessary to provide a proof for our statement.

Dietary Intake and Plasma Levels of Antioxidant Vitamins in Health and Disease: A Hospital-based Case-control Study

Of 1667 subjects that attended the hospital, 1335 were patients with diagnosed medical conditions, together with 202 randomly selected, apparently healthy controls from the same population, were studied in detail for demographic variables, dietary and biochemical data. Dietary consumption of antioxidant vitamins A, E, and C and β-carotene and soluble fibre was lower in the majority of conditions compared to controls. Plasma concentrations of vitamin C and β-carotene were significantly lower in all patient groups. Reduced vitamin E levels were noted in patients with cardiovascular diseases, stroke, Parkinsons disease, chronic renal failure, nephrotic syndrome, type A behaviour, post-partum psychosis, burns, liver diseases, cancer, rheumatoid arthritis and aluminium phosphide poisoning. Lipid peroxides (thiobarbituric acid reactive substances), which are an indicator of oxygen-derived free radical damage, were significantly higher than controls in most conditions and marginally higher in respiratory and ps...

Randomized, controlled trial of antioxidant vitamins and cardioprotective diet on hyperlipidemia, oxidative stress, and development of experimental atherosclerosis: The diet and antioxidant trial on atherosclerosis (DATA)

SummaryThe effects of administration of guava and papaya fruit (100 g/day), vegetables, and mustard oil (5 g/day) (group A); antioxidant vitamins C (50 mg/day) and E (30 mg/day) plus betacarotene (10 mg/day) (group B); a high-fat (5–10 g/day) (group C); or a low-fat (4–5 g/day) diet (group D) were compared over 24 diet weeks in a randomized fashion, while all groups of rabbits (five in each of four groups) received a hydrogenated fat diet (5–10 g/day) for a period of 36 weeks. After 12 weeks on the high-fat diet, each group of rabbits had an increase in blood lipoproteins. The fruit and vegetable-enriched prudent diet (group A) caused a significant decline in blood lipids at 24 and 36 weeks, whereas the lipid levels increased significantly in groups C and D. Group A also had a significant rise in vitamin E (2.1 Umol/l), C (10.5 Umol/l), A (0.66 Umol/l), and carotene (0.08 Umol/l) and a decrease in lipid peroxides (0.34 nmol/ml at 36 weeks, whereas the levels were unchanged in groups C and D. Group B rabbits had a significant and greater increase than group A in plasma vitamins E, C, A, and carotene; a rise in HDL cholesterol; and a greater decrease in lipid peroxides after 24 and 36 weeks of treatment. After stimulation of lipid peroxidation in all rabbits, 3 of 5 group C and 2 of 5 group D rabbits died due to coronary thrombosis, whereas in groups A and B there were no deaths, indicating that antioxidant therapy can provide protection against lipid peroxidation and free radical generation. Aortic lipids and sudanophilia, indicating atherosclerosis, were significantly higher in groups C and D than in groups A and B. Fatty streaks and atheromatous and fibrous plaques were noted in all the rabbits in groups C and D. Intimal fibrosis and medial degeneration were also present in the group C rabbits. While group A (36.4±4.4 µm) and group B (37.1±4.2 µm) rabbits had minimal coronary artery plaque sizes, group C (75.4±10.6 µm) and group D rabbits (69.5±6.2 µm) had significantly greater plaque sizes. Aortic plaque sizes were also greater in groups C and D than in groups A and B. It is possible that combined therapy with antioxidant vitamins C, E, and carotene, and a diet rich in antioxidants, could independently inhibit free radical generation and the development of atherosclerosis.