Fabien De Meester

Prevalence and risk factors for prehypertension and hypertension in five Indian cities

Background There are few studies detailing the prevalence of prehypertension and hypertension in India. Methods Men and women, over 25 years of age were included. After completion of a dietitian-administered questionnaire followed evaluation by a physician, physical examination and blood pressure measurement. Cross-sectional survey screened 6940 subjects, (3507 men (M), 3433 women (W): 1993-96) from cities located in five corners of India (Kolkata, n = 900; Nagpur, n = 894; Mumbai, n = 1542; Thiruanantpuram, n = 1602; Moradabad, n = 2002). Prehypertension (BP 130-139/85-89 mm Hg) and hypertension (BP ≥ 140/90 mm Hg) were diagnosed according to the European Society of Cardiology criteria. Results Prevalence of prehypertension and hypertension, respectively, was significantly greater in South India (Trivandrum: W 31.5; 31.9%; M 35.1; 35.5%) and West India (Mumbai: W 30.0; 29.1%; M 34.7; 35.6%) compared to North India (Moradabad: W 24.6; 24.5%; M 26.7; 27.0%) and East India (Kolkata: W 20.9; 22.4%; M 23.5; 24.0%). Subjects with prehypertension and hypertension were older, had a higher BMI, central obesity and a sedentary lifestyle. They had a higher salt and alcohol intake, with greater oral contraceptive usage (W). Multivariable logistic regression analysis revealed strong positive associations of hypertension with age, central obesity, BMI, sedentary lifestyle, salt and alcohol intake and oral contraceptive usage (W). Fruit, vegetable and legume intake showed inverse associations, tobacco intake showed none. One in four with hypertension was aware of their diagnosis and of those receiving treatment, one in three had well-controlled hypertension. Conclusions There is little awareness that prehypertension and hypertension are public health issues in India. Ageing population, central obesity, sedentary lifestyle, excessive salt and alcohol, lower fruit, vegetable and legumes intake increase risk for blood pressure elevation.

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.

Effects of Nutraceuticals on Genetic Expressions

The prevalence and mortality due to multifactorial polygenic diseases; hypertension, coronary artery disease (CAD), diabetes and cancer vary depending upon genetic susceptibility and environmental precursors because they have identifiable mendelian subsets. Rapid changes in diet and lifestyle, may influence heritability of the variant phenotypes that are dependent on the nutraceutical or functional food supplementation for their expression. It is possible to recognize the interaction of specific nutraceuticals, with the genetic code possessed by all nucleated cells. There is evidence that South Asians have an increased susceptibility to CAD, diabetes mellitus, central obesity and insulin resistance at younger age, which may be due to interaction of gene and nutraceutical environment. These populations appear to have enherited predisposition and may have interaction of internal nutritional status and environmental factors. Higher intake of refined starches and sugar increases generation of super oxide anion in the leucocytes and mononuclear cells, and free fatty acids (FFA), as well as higher amount and activity of nuclear factor-kB (NF-kB), a transcriptional factor regulating the activity of at least 125 genes, most of which are pro-inflammatory. Glucose intake also causes an increase in two other pro- inflammatory transcription factors; activating protein-1 (AP-1) and early growth response protein-1 (Egr-1), the first regu- lating the transcription of matrix metallo-proteinases and the second modulating the transcription of tissue factor and plasminogen activator inhibitor-1. Refined food, mixed meal induces activation of NF-kB associated with free radicals generation by mononuclear cells. The super oxide anion is an activator of at least two major pro-inflammatory transcrip- tion factors, NF-kB and AP-1. Increased intake of linoleic acid, saturated fat, trans fat and refined starches and sugars can increase the generation of free radicals and activate the NF-kB, leading to rapid expression of proinflammatory genes. It is possible that nutraceuticals; antioxidants, micronutrients, minerals, vitamins, coenzyme Q10 and w-3 fatty acids may in- hibit the generation of super oxide and suppress NF-kB as well as AP-1, and Egr-1 leading to suppression of phenotypic expressions. It is known that genes are important in determining enzymes, receptors, cofactors, structural components in- volved in regulation of blood pressure, the metabolism of lipids, lipoproteins and inflammatory and coagulation factors that are involved in determining individual risk for vascular diseases and diabetes. It seems that these phenotypic expres- sions may be silenced by targeting simple sequence differences known as single nucleotide polymorphisms by nutraceuti- cals and slowly absorbed wild foods rich in micronutrients and antioxidants.

Nutrition in Transition from Homo sapiens to Homo economicus

The food and nutrient intake among Paleolithic Homo sapiens, hunter-gatherers and among Asian and Homo economicus Western populations shows marked variations. Economic development and affluence may be associated with a decrease in the consumption of omega-3 fatty acids, vitamins, antioxidants and amino acids and significant increase in the intakes of carbohydrates, (mainly refined), fat (saturated, trans fat and linoleic acid) and salt compared to the Paleo- lithic period. The protein or amino acid intake was 2.5 fold greater (33 vs. 13%) in the Paleolithic diet Homo sapiens compared to modern Western diet consumed by Homo economicus populations. Approximately 10,000 years ago, prior to the Agricultural Revolution, our diet was based on an enormous variety of wild plants. However, today about 17% of plant species provide 90% of the worlds food supply which is mainly contributed by grains produced by fertilizer based on rapidly grown crops which may result in a decrease in nutrient density and increase in energy. Wheat, corn and rice ac- count for three fourths of the worlds grain production on which humans are dependent for their food supply. Grains are high in omega-6 fatty acids and carbohydrates and low in omega-3 fatty acids and antioxidants compared to leafy green vegetables. It has been estimated that diet of Homo sapiens was characterized by higher intakes by essential and non- essential amino acids, calcium, potassium, magnesium, flavonoids and w-3 fatty acids whereas modern Western diet of Homo economicus has excess of energy-rich refined carbohydrates, w-6, trans fat and saturated fat and low in protective nutrients. The consumption of such diets in wealthy countries in conjunction with sedentary behavior is associated with increased prevalence of morbidity and mortality due to noncommunicable diseases (NCDs).

Nutritional aspects of epigenetic inheritance

The impact of diet and environmental factors on genes concerned with epigenetic inheritance and the mechanism of evolution has grown significantly beyond the Modern Synthesis period. Epigenetic inheritance is the passing of phenotypic change to subsequent generations in ways that are outside the genetic code of DNA. Recently, polymorphisms of the human Delta-5 (fatty acid desaturase, FADS1) and Delta-6 (FADS2) desaturase genes have been described as being associated with the level of several long-chain n-3 and n-6 polyunsaturated fatty acids (PUFAs) in serum phospholipids. Increased consumption of refined starches and sugar increases the generation of superoxide anion in the tissues and free fatty acids (FFA) in the blood. There is an increased amount and activity of nuclear factor-κB (NF-κB), a transcriptional factor regulating the activity of at least 125 genes, most of which are pro-inflammatory. The consumption of glucose may be associated with an increase in 2 other pro-inflammatory transcription factors: activating protein-1 (AP-1), and early growth response protein-1 (Egr-1). AP-1 regulates the transcription of matrix metallo-proteinases and Egr-1 modulates the transcription of tissue factor and plasminogen activator inhibitor-1. It is possible that a complex set of factors, including nutritional factors, come into play during epigenetic inheritance.

Essential and Non-Essential Amino Acids in Relation to Glutamate

The protein intake during the Palaeolithic period has been estimated to be two and a half fold greater than current recommendations. Hydrogen, nitrogen, oxygen and carbon atoms are important components of essential and nonessential amino acids which are components of proteins. These simple molecules play an important role in the human body. The 22 known amino acids, essential and nonessential, affect a broad range of physical and mental processes. Recent studies indicate that amino acids are cell signalling molecules as well as being regulators of gene expression and the protein phosphorylation cascade. The majority of the neurotransmitters is composed of amino acids and can influence biological functions related to brain-body interactions. Amino acids are key precursors for syntheses of hormones and low-molecular weight nitrogenous substances with each having enormous biological importance. Physiological concentra- tions of amino acids and their metabolites; nitric oxide, polyamines, glutathione, taurine, thyroid hormones, and serotonin are required for the biological functions in our body. These metabolites are known to be protective against cardiovascular diseases and degenerative diseases of the brain. However, increased concentrations of amino acids and their products (e.g., ammonia, homocysteine, and asymmetric dimethylarginine) are pathogenic factors for neurological disorders, oxidative stress and cardiovascular disease. Glutamate is a nonessential amino acid present in many foods that is consid- ered protective against obesity and cardiovascular diseases. Therefore a balance between amino acids and other nutrients appears to be important for normal physiological functions without any adverse effects.

Coenzyme Q10 in Heart and Brain Diseases

Background: Several cardiovascular, neurological and other diseases are associated with coenzyme Q10( CoQ) deficiency. The objective is to evaluate possible benefits of ubiquinone supplementation in cardiovascular diseases and degenerative diseases of the brain. Methods: An internet search in PubMed, Vitasearch, In Circulation. Net, till 2008, discussions with colleagues, own experiences. Results: Ubiquinone (Coenzyme Q10 ) deficiency has been observed in several cardiovascular and neurological diseases. CoQ10 has strong influence on lipid metabolism, oxidation of blood lipids, vascular inflammation and on the cell mem- branes of cardiac and arterial cells and neurons. These pathogenetic mechanisms seem to be important in patients with neurological and cardiac disease as well as in brain-heart connection. Its supplementation has several beneficial effects in- cluding the stabilisation of atherosclerotic plaque and decreasing the size of myoacardial infarction and the protection of neurons. Antioxidant properties of CoQ10 are responsible for the prevention of many drug side effects. Several studies have suggested the beneficial effect of CoQ10 in neuro-cardiovascular diseases, that will require further confirmation. Adverse effects such as nausea and vomiting may be reduced by using highly bio-available brands, that reduce the oral dosage of COQ. Conclusions: CoQ10 is still in the investigational stages and the list of possible indications related to brain and heart dis- eases and their linkage, appears to be quite extensive. There is still the need for a number of large, double blind multicen- ter, randomized, controlled clinical trials, in order to confirm the possible beneficial effects of CoQ10 supplementation in different neurocardiological conditions.

Effect of Brain Derived Neurotrophic Factor, In Relation to Diet and Lifestyle Factors, for Prevention of Neuropsychiatric and Vascular Diseases and Diabetes

Background: Brain-derived neurotrophic factor (BDNF) is a major neurotrophin which may have promise to be a nutraceutical of this decade. It has a documented role in neurogenesis, angiogenesis, and neuronal survival. BDNF can have beneficial effects on several cardio-metabolic and neuro-psychiatric disorders, indicating that it is important in brain- body interactions. Diet and lifestyle factors may also have an influence on BDNF levels. In this review, we examine the beneficial role of BDNF on risk factors of vascular diseases, type 2 diabetes mellitus and anxiety disorders. Methods: In- ternet search and discussion with peer colleagues. Results: Majority of the BDNF (70-80%) is derived from dendrite of neurons but it is also present in other body tissues. BDNF controls the food intake and appetite as well as lipid and glu- cose metabolism. Sedentary behavior and tobacco intake may be associated with BDNF deficiency. Lower serum concen- tration of BDNF and higher vascular endothelial growth factor (VEGF) concentrations were associated with increased risk of incident stroke/TIA. BDNF may serve as an intermediate biomarker for subclinical vascular disease and may also have biological potential to serve as a therapeutic target for primary and secondary prevention of vascular diseases, as well as clinical and subclinical vascular brain disease. BDNF deficiency has been observed in association with anxiety, depres- sion, insomnia, dementia, insulin resistance, type 2 diabetes and vascular diseases. The phenotypes associated with insulin resistance are at increased risk for developing cognitive decline and neuro-degeneration resulting in vascular dementia, and depression as well as diabetes mellitus and metabolic syndrome, which are risk factors for CVDs. BDNF may be ad- ministered as nutraceutical due to its protective influence on BDNF concentrations, insulin receptors and hypothalamic dysfunction leading to beneficial effects on cardiovascular risk and neuropsychological dysfunction. It is proposed that omega-3 fatty acids and moderate physical activity may enhance BDNF release. Conclusions: It is possible that circulat- ing BDNF deficiency is a risk factor for obesity, CVDs and diabetes as well as risk factor for neuropsychiatric diseases. BDNF administration may modify the risk of clinical and subclinical stroke, depression, and dementia as well as of obe- sity and type 2 diabetes.

EDITORIAL Perspectives on Chocolate Consumption and Risk of Cardiovascular Dis- eases and Cognitive Function

Flavonoid deficiency in the diet is a risk factor for cardiovascular diseases (CVDs) and other chronic diseases. Recent studies indicate that increased consumption of chocolates may be associated with decreased risk of CVDs and in- sulin resistance, inflammation and hyperlipidemia. In the present editorial, we have sought supporting evidence for such claims. It is possible that cocoa consumption (30-1000mg/day) in the form of dark chocolates can protect against hyper- tension, stroke, atherosclerosis, insulin resistance and memory dysfunction. Further research is necessary to prove this finding.

Nutrition and Behaviour: The Role of 3 Fatty Acids

This review article gathers evidence on the potential relationship between dietary intake of � 3 polyunsaturated fatty acids (� 3 PUFAs) and mental function. Several pieces of evidence that � 3 PUFAs influence affective and cognitive function are presented. Although published data and results available in the field remain limited and sometimes ambiguous, they have shed a new light on the role of proper diet in general, � 3 PUFAs in particular, in many mental disorders and dysfunctions, including depression and cognitive decline in aging. The analysis of the influence of fatty acids on human health allows us to formu- late a new, more holistic approach to both prevention and treatment of psychological disorders and dysfunctions. What is more, it appears that � 3 PUFAs have a beneficial influence on mental function in healthy people as well. The currently available data concerning the influence of fatty acids on behaviour and mental function are still insufficient and suffer so far from lack of standard determination of background, intermediairy and endpoint omega-6/3 ratios in plasma lipids of patients involved in both epidemiological and intervention studies. There is a great need for further refined trials in the field.