Issue 2003-3

2003; Vol 3(1): 1-25
RB Singh (1), Agnieszca Wilczynska (2), R K Agarval (3), A V Sotnikov(4), A V Gordienko(5), D V Nosovich (6).3Technomed Holdings LLC Publishing House, 
Moscow, Russian Federation, 4Military medical academy named after S.M. Kirov, St. Petersburg, Russian Federation,5International College of Cardiology, 
Thornhill, Canada,6Sechenov University, Ministry of Health, Moscow, Russian Federation.
Correspondence: Dr Agnieszka Wilkzynska,PhD, The Tsim Tsoum Institute, Krakow, Poland,  Email: <> 
Abstract. Nutritional transition from poverty to economic development is associated with emergence of non-communicable diseases (NCDs). The last 
decade of the last century offered us an opportunity to initiate action to counter growing epidemics of cardiovascular diseases (CVDs) and metabolic 
diseases in both developed and developing countries. The learning of the methods of prevention by the populations, was associated with a decrease in 
CVD in the western world but obesity continued to increase, resulting into an increase in the metabolic syndrome in both developed and developing economies. 
Western diet is characterized with energy dense, refined, ready prepared foods with a high glycemic index (e.g., refined starches; bread, biscuits, candies, 
cornflakes, potato chips, cola drinks and sugar) and unhealthy lipids (e.g., trans fats, high saturated fat) poor in w-3 fatty acids, phytochemicals and fiber. 
Such diets have been adopted by increased number of people and populations in the developed countries and in the urban populations of middle income 
countries in the last few decades. Apart from dietary factors, late night sleep and night shift working may be associated with risk of CVDs and diabetes. 
These diets and lifestyle factors are known to predispose inflammation and the epidemic of NCDs. CVDs, diabetes mellitus, obesity, cancer, autoimmune 
diseases, rheumatoid arthritis, asthma and depression are associated with increased production of thromboxane A2(TXA2), leucotrienes, prostacyclin, 
interleukins-1 and 6, tumor necrosis factor-alpha and C-reactive proteins. Increased dietary intake of w-6 fatty acids may have adverse effects on all 
these biomarkers as well as atherogenicity of cholesterol which have adverse pro-inflammatory effects resulting into NCDs. Mediterranean diet rich in fruits, 
vegetables, nuts, canola oil, olive oil characterized with low w-6/w-3 ratio in the diet, as well as physical activity, and meditation can modulate inflammation 
as well as body-mind interactions and may be protective against risk of CVD and all cause mortality.
Keywords. Polyunsaturated fatty acids, inflammation, western foods, night shift.
 How to cite: 
Mahmood Moshiri, Sara Sarrafi-Zadeh, Mahsa Jalili; Halberg Hospital and Research Institute, Moradabad, Department of Foods Sciences, 
University of Mysore, Mysore, India
Correspondence:  Dr Mahmood Moshiri, MD, International College of Nutrition, Thornhill, On, Canada,<> 
Abstract. The example for epigenetic inheritance is the yellow Agouti mouse, an epigenetic biosensor for nutritional and environmental changes. These 
fat and yellow mice owe their appearance to epigenetic modification that removes methyl groups from the normally methylated agouti gene. In a 
developing mouse fetus, if the above modification occurs shortly after fertilization, the baby mouse may exhibit the yellow fur and obese phenotype 
with greater risk of developing metabolic syndrome, cardiovascular disease (CVD) and diabetes. Since, epigenome is limited to the surface of the gene, 
the genetic sequence remains unchanged from normal mice. It has been observed that alteration of the nutrient intake to serve as methyl group donors 
in mouse mothers, was associated with methylation or demethylation of the agouti gene. Increased supplementation of choline, betaine, folic acid and 
vitamin B12 in the diet of pregnant yellow agouti mice was able to decrease the incidence of deleterious phenotypes in offspring, by donating methyl group 
and allowing for the re-methylation of the agouti gene. If these mice be born with the agouti phenotype, they can pass that deleterious epigenetic trait 
in their offspring, regardless of their diet during pregnancy. This landmark study indicates   that nutrients can cause phenotypic changes which can pass on 
through cell division and mating to the offspring due to their possible influence on (natural) selection. It is possible therefore to say; that we are what we 
eat and what our parents ate, and potentially what our grand parents ate which would be modification of the old Sanskrit saying ‘Aham Annam’   from the 
ancient Vedas (5000BCE). There is a need to study the effects of low ω-6/ω-3 fatty acid ratio diet, and other nutrients; arginine, taurine, cysteine, 
coenzyme Q10 on the re-methylation of the agouti gene and their effects on phenotypic variations. However this mode of inheritance needs to penetrate 
more than a few generations before it earns a place in evolutionary concept.
Keywords. DNS methylation, chromatids, hypomethylation, hypermethylation.
How to cite: Moshiri M, Sarrafi-Zadeh S, Jalili M. Nutritional modulators of epigenetic inheritance. Int J Clin Nutrition 2004; 4: 6-10. 
RB Singh(1), Lekh Juneja(2), Ghizal Fatima(3), Poonam Tiwari (4) 1Halberg Hospital and Research Institute; Moradabad, India. 2Tayo Kagaku, Japan; 
3Era Medical College, Lucknow, India, 4RML Hospital, Lucknow, India
Association between brain dysfunction and pathogenesis of metabolic syndrome leading to cardiovascular diseases (CVDs), type 2 diabetes (T2DM) 
is an interesting hypothesis.
Increased intake of  refined carbohydrates, linoleic acid, saturated and total fat and low dietary n-3 fatty acids and other long chain polyunsarurated 
fatty acids(PUFA) in conjunction with sedentary behaviour and mental stress and various personality traits can predispose inflammation in the adipocytes 
leading to obesity and  central obesity. There may be increased sympathetic activity with increased secretion of catecholamine, cortisol and serotonin and 
pro-inflammatory cytokines that appear to be underlying mechanisms of metabolic syndrome. Apart from these alterations, these is an underlying long 
chain PUFA deficiency, which may increase the susceptibility of the neurons to damage, 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 long chain 
PUFA, especially omega-3 fatty acids, which are incorporated in the cell membrane phospholipids, it is possible that the treatment with these 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 acetyle- choline in the hippocampus. It is possible that marginal deficiency of long chain PUFA, 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 also enhance the release of tumor necrosis factor-alpha, interleukin-1,2 and 6 and cause neuronal dysfunction. However, supplementation 
of these fatty acids may prevent the brain damage leading to prevention of CVDs and T2DM in the concerned subjects.
Keywords. Diet, polyunsaturated fatty acids, inflammation, western diet.
How to cite.  RB Singh (1), Lekh Juneja(2), Ghizal Fatima(3), Poonam Tiwari (4) Metabolic syndrome: a dysfunction of the brain. 
Int J Clin Nutrition 2003; 3: 11-15.

Kumar Kartikey (1), Brajesh Kidyore(2), Y A Somsunder(3); Howarth P.(4) , Viola Vargova (5), Zelmira Macejova (6); 1,2,3Department of Orthopedics, 
Sidhartha Medical College, Tumkur (AP), India; 4,5,6Faculty of Medicine,  PJ Safaric University, Slovakia
Correspondence:  Dr Kumar Kartikey,MBBS,MS(Orthopedics),FICN, Senior Resident, Teerthankar Medical College, Halberg Hospital and Research Institute, 
Civil Lines, Moradabad- 10 (UP) 244001, India, email,  <>
Abstract: There is evidence that calcium, magnesium, vitamin D, proteins,  antioxidants and w-3 fatty acids intakes are inversely associated with risk of 
osteoporosis and hip fractures. This study aims to examine the association of food consumption pattern and w-6/w-3 fatty acid ratio of the diet with 
inflammation and hip joint fractures. After written informed consent and approval from ethic committee of the college, 60 patients, having fracture 
neck of femur  and 95 control subjects above 50 years of age were included in this case control study. The results revealed that the fracture was  more 
common in male than female. Fruits, vegetables and legume (165  ±12.6 vs. 205±15.8g/day, P<0.03) as well as milk products (milk, curd, butter etc) 
consumption (205+25.8 vs.  318±31.5g/day,P<0.05) were significantly lower and w-6 rich oils and saturated fat intake was significantly higher among 
patients with fractures compared to control subjects, respectively. Omega-3 fatty acids intakes were significantly lower among patients with fractures 
(0.45± 0.74 g/day, P<0.05).Osteoporosis (92.0%), trivial trauma (92.0%), physical inactivity (80.0%), diabetes mellitus(21.6%) were common among patients 
with hip fracture. Multivariate logistic regression analysis showed that the intakes of fruit, vegetable and legume( odds ratio 1.12, confidence interval 
(CI) 1.02-1.21, P<0.05), physical activity(OR 1.36, CI 1.22-1.52, P<0.05), w-3 fatty acids (OD1.05, 0.92-1.17, P<0.01) intake were inversely associated 
with fracture, whereas w-6/w-3 ratio (OD 1.33, CI 1.18-1.47,P<0.01) interleukin-6, (OD1.11, CI 1.02-1.19, P<0.01), tumor necrosis factor-alpha
(OD,1.09, CI 1.01-1.17, P<0.01)  were positively associated with fracture. The findings showed that increased consumption of fruit, vegetable and legume, 
milk products and w-3 fatty acid and low w-6/w-3 ratio diet as well as physical activity may be protective against hip joint fractures. 
Key words:  Nutrition, dietary pattern, fatty acids, inflammation, bone disease, cytokines.
How to cite: Kartikey K,  Kidyore B, Somsunde YA; Howarth P, Vargova V, Zelmira Macejova Z.  Effects of dietary omega-6/omega-3 fatty acid ratio on 
inflammation and risk of hip fracture. Int J Clin Nutrition 2003; 3: 16-20.

Adarsh Kumar(1), RB Singh(2), Manoj Saxena(3), MA Niaz (4), Pronobesh Chattopadhyay(5). 1Government Medical College, Amritser, India; 
2,3Medical Hospital and Research Institute, Moradabad, 5IFTM College of Pharmacy, Moradabad, India
Correspondence:  Dr Adarsh Kumar,MD,DM, FICN, Department of Medicine, Government College, Amritsar(Punjab), India
Abstract. Environmental risk factors are known to cause mitochondrial dysfunction which enhances the generation of radical oxygen species (ROS), 
leading to damage mtDNA, nDNA, proteins, and lipid membranes. Experimental studies indicate that lacking the mitochondrial antioxidant enzyme 
manganese-superoxide dismutase (SOD) develop dilated cardiomyopathy. Treatment with L-acetyl-carnitine and coenzyme Q10 improves cardiac 
function in patients with cardiomyopathy. CoQ10 which is a potent antioxidant is important in OXPHOS as well as in mitochondrial function. L-Carnitine 
also regulates mitochondrial function and may have synergistic effects, when combined with CoQ10. In a clinical study, including 18 patients with dilated 
cardiomyopathy diagnosed by 2-D echocardiography, 10 patients were randomized to CoQ10+ L-carnitine and 8 patients to placebo group. Carni Q-gel 9 
softgels (3 with each meal thrice daily), which provide a total of 270 mg ubiquinol and 2250 mg L-carnitine daily, or 9 matching placebos were administered 
daily to each patient during the 12-week period.TNF-alpha, IL-6, TBARS, MDA and diene conjugates were raised in both the groups at base line. Both groups 
had significant CoQ10 deficiency in the plasma (normal range 0.5 to 1.5 ug/ml). However, after 12week treatment with this combination, there was a 
significant improvement in the clinical and biochemical parameters of these patients. Serum concentration of CoQ10 (0.21±0.11 vs 0.19±0.10  ug/ml, 
normal 0.5 to 1.5 ug/ml) were deficient but comparable at baseline. However, after 12week treatment, there was a significant increase in CoQ10 in 
the intervention group without any rise in the placebo group. (2.7±1.2 vs 0.76±0.14 ug/ml, P<0.001). Further studies are necessary to confirm our results.
Key Words. Cardiac, antioxidant, mitochondrial, oxidative stress,
How to cite: Kumar A, Singh RB, Saxena M, Niaz MA, Chattopadhyay P. Coenzyme  Q10 and carnitine in cardiomyopathy. Int J Clin Nutrition 2003; 3: 21-25.