More Pics of Breckenridge

We had sometime in between conference sessions to go hiking.

The first thing we saw was what looked like a mini Indian tepee.

Climbing up the ski slope with the thin air at nearly 3000m made each step a breathless endeavour. But the view was breathtaking!

Some struggled real hard...

But these 2 immunologists were discussing immunology (what else?) on their way up despite having to gasp for air between words...

It rained, but only for a while.

Perseverance in action...

The visual treat was just fabulous higher up

The walk down was beautiful too.

Psyllium – The Natural Way To Reduce Your Cholesterol Levels

It is great to be back in sunny Singapore after a fruitful trip to Breckenridge!

Today, I would like to share a little about this wonder fiber that nature has provided for us, especially for those who need to control their high cholesterol. Our laboratory has independently conducted experiments to test the cholesterol-lowering effects of psyllium and I am therefore very convinced of its effects (read our paper if you want the details).

Benefits of Dietary Fiber

It has been known for a long time that a high intake of fiber in our daily diet is good for health. A high-fibre diet is associated with reduced risks of heart disease, colon cancer and obesity [1]. The health benefits of consuming large amount of dietary fiber were first suggested more than 30 years ago [2]. Since then, evidences of the link between dietary fiber and heart disease have accumulated from population studies [3-6] and clinical trials [7-8]. There are two main types of dietary fiber - soluble and insoluble. Insoluble fiber has not been shown to exhibit a consistent cholesterol-lowering effect. In contrast, consuming a high-fiber diet containing viscous soluble fiber is known to significantly lower the total and low-density lipoprotein (LDL) cholesterol levels, which is the bad cholesterols in the blood [9-11]. What is Psyllium? Psyllium is pronounced "sil-ee-um" (the "P" is silent). It is derived from Plantago ovato, or plantain plants, and is grown mainly in India, Spain and France. The outer part of the psyllium seed, called the husk, is the portion that has the cholesterol-lowering property. Psyllium husk is easily available in health food stores. It can be consumed by adding into fruit juice or any drink, or added into breads, cereals, and pasta. Some cereal products are enriched with psyllium.

Psyllium Husk

What you are more likely to see when you buy a packet/bottle of psyllium husk

Cholesterol-lowering properties of psyllium
Let us try to understand how the lowering of the cholesterol can be achieved. Very simply put, this can be brought about by either causing the body to get rid of more cholesterol or to make less of it. It appears that psyllium works through the former, that is, it helps the body to get rid of more cholesterol through the formation of bile acid [12], which is excreted out along with the stool. This process accounts for 40–50% of the daily elimination of cholesterol [13,14]. The liver is the main site of bile acid formation.

Among the various forms of viscous soluble fibers, psyllium husk appears to be the most effective in lowering cholesterol levels [15,16] and has the least adverse side effects.17 The effect of psyllium husks on fasting plasma cholesterol has been evaluated in individuals with high-cholesterol, obesity, or diabetes [18-19]. In general, these studies show that psyllium husk consumption could bring about a 5% reduction in total cholesterol and 7–8% reduction in LDL cholesterol, which were sustainable in the long term [20, 21].

How much of psyllium should I consume to lower my cholesterol and for how long?
Clinical trials have shown that typically, about 10g per day (over 2-3 doses) for about 2 months is sufficient to achieve a cholesterol-lowering effect.


Reference List
1. D. Kritchevsky and C. Bonifield, Dietary fiber in health and disease, Plenum Press, New York (1997).

2. D.P. Burkitt and H.S. Trowell, Refined carbohydrate foods and disease: some implications of dietary fibre, Academic Press, London (1975).

3. K.T. Khaw and E. Barrett-Connor, Dietary fiber and reduced ischemic heart disease mortality rates in men and women: a 12-year prospective study, Am J Epidemiol 126 (1987), pp. 1093–1102.

4. C.G. Humble, A.M. Malarcher and H.A. Tyroler, Dietary fiber and coronary heart disease in middle-aged hypercholesterolemic men, Am J Prev Med 9 (1993), pp. 197–202.

5. D. Kromhout, E.B. Bosschieter and C. de Lezenne Coulander, Dietary fibre and 10-year mortality from coronary heart disease, cancer, and all causes. The Zutphen study, Lancet 2 (1982), pp. 518–522.

6. A. Wolk, J.E. Manson, M.J. Stampfer, G.A. Colditz, F.B. Hu and F.E. Speizer et al., Long-term intake of dietary fiber and decreased risk of coronary heart disease among women, JAMA 281 (1999), pp. 1998–2004.

7. I. Hjermann, K. Velve Byre, I. Holme and P. Leren, Effect of diet and smoking intervention on the incidence of coronary heart disease Report from the Oslo Study Group of a randomised trial in healthy men, Lancet 2 (1981), pp. 1303–1310.

8. A.C. Arntzenius, D. Kromhout, J.D. Barth, A.V. Bruschke and B. Buis et al., Diet, lipoproteins, and the progression of coronary atherosclerosis The Leiden Intervention Trial, N Engl J Med 312 (1985), pp. 805–811. M.L. Burr, A.M. Fehily, J.F. Gilbert, S. Rogers, R.M. Holliday and P.M. Sweetnam et al., Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: Diet And Reinfarction Trial (DART), Lancet 2 (1989), pp. 757–761.

9. D.J. Jenkins, T.M. Wolever, A.R. Leeds, M.A. Gassull, P. Haisman and J. Dilawari et al., Dietary fibres, fibre analogues, and glucose tolerance: importance of viscosity, Br Med J 1 (1978), pp. 1392–1394.

10. S.R. Glore, D. Van Treeck, A.W. Knehans and M. Guild, Soluble fiber and serum lipids: a literature review, J Am Diet Assoc 94 (1994), pp. 425–436.

11. D.J. Jenkins, C.W. Kendall, M. Axelsen, L.S. Augustin and V. Vuksan, Viscous and nonviscous fibres, nonabsorbable and low glycaemic index carbohydrates, blood lipids and coronary heart disease, Curr Opin Lipidol 11 (2000), pp. 49–56.

12. C.C. Schwartz, M. Berman, Z.R. Vlahcevic and L. Swell, Multicompartmental analysis of cholesterol metabolism in man, J Clin Invest 70 (1982), pp. 863–876.

13. D.M. Heuman, Z.R. Vlahcevic, M.L. Bailey and P.B. Hylemon, Regulation of bile acid synthesis. 11 Effect of bile acid feeding on enzymes regulating hepatic cholesterol and bile acid synthesis in the rat, Hepatology 8 (1988), pp. 892–897.

14. Z.R. Vlahcevic, D.M. Heuman and P.B. Hylemon, Regulation of bile acid synthesis, Hepatology 13 (1991), pp. 590–600.

15. P. Bell, K.J. Hectorn, H. Reynolds and D.B. Hunninghake, Cholesterol lowering effects of soluble-fiber cereals as part of a prudent diet for patients with mild to moderate hypercholesterolemia, Am J Clin Nutr 52 (1990), pp. 1020–1026.

16. J.W. Anderson, A.E. Jones and S. Riddell-Mason, Ten different dietary fibers have significantly different effects on plasma and liver lipids of cholesterol-fed rats, J Nutr 124 (1994), pp. 78–83.

17. J.W. Anderson, D.A. Deakins, T.L. Floore, B.M. Smith and S.E. Whitis, Dietary fiber and coronary heart disease, Crit Rev Food Sci Nutr 29 (1990), pp. 95–147.

18. A.C. Frati-Munari, J.A. Fernandez-Harp, M. Becerril, A. Chavez-Negrete and M. Banales-Ham, Decrease in plasma lipids, glycemia and body weight by Plantago psyllium in obese and diabetic patients, Arch Invest Med 14 (1983), pp. 259–268.

19. L.P. Bell, K. Hectorne, H. Reynolds, T.K. Balm and D.B. Hunninghake, Cholesterol-lowering effects of psyllium hydrophilic mucilloid Adjunct therapy to a prudent diet for patients with mild to moderate hypercholesterolemia, JAMA 261 (1989), pp. 3419–3423 .

20. J.W. Anderson, L.D. Allgood, A. Lawrence, L.A. Altringer, G.R. Jerdack and D.A. Hengehold et al., Cholesterol-lowering effects of psyllium intake adjunctive to diet therapy in men and women with hypercholesterolemia: meta-analysis of 8 controlled trials, Am J Clin Nutr 71 (2000), pp. 472–479.

21. J.W. Anderson, M.H. Davidson, L. Blonde, W.V. Brown, W.J. Howard and H. Ginsberg et al., Long-term cholesterol-lowering effects of Psyllium as an adjunct to diet therapy in the treatment of hypercholesterolemia, Am J Clin Nutr 71 (2000), pp. 1433–1438.

ANRIL, Chromosome 9p21 and Coronary Artery Disease

I had just attended a talk by Dr Ruth McPherson on the topic of “Genetic Insights into Coronary Artery Disease”. She spoke about her genomewide association study (GWAS) which she had recently published in Science. For a quick review of the recent developments in GWAS of CAD, you can refer to my editorial in the European Heart Journal.

GWAS have consistently pointed to chromosome 9p21 and its robust association with CAD. Several replication studies have confirmed this fact. Approximately 25% of Caucasians carry 2 copies of the risk allele and have a 1.5 fold higher risk for CAD. The increased risk associated with this allele is independent of all known CAD risk factors. Thus the identification of region suggests that a novel biological pathway may be involved in atherosclerosis.

The 9p21 locus overlaps a newly annotated antisense noncoding RNA in the INK4 locus splice variant (ANRIL or DQ485453). ANRIL spans 126.3kb and overlaps at its 5’end with CDKN2B (p15INK4b). It consists of 19 exons, of which the first 12 exons are conserved whereas exons 13-19 are subjected to alternative splicing.

It would be exciting to see how the investigations of the 9p21 region would unfold in the near future!

Breckenridge

After more 24 hours of flying and in transit, I have finally arrived in Breckenridge, a small highland town in Colorado, USA to attend the Keystone Symposium on Metabolism and Cardiovascular Risk . It was a pity that I had arrived late in the evening and was unable to see sceneries of the mountains on the way here. Nevertheless, I had some time this morning to take a walk around The Great Divide, the lodge where I am staying. A picture is worth a thousand words. So here are the pics!

Aerial shot while on flight from San Francisco to Denver.

Can anyone tell me what are those disc-like vegetation in the midst of the desert? I saw a few clusters of these.

Sky view of Colorado

Breckenridge
Breckenridge

My research interests

I have two major research focuses

I. Genetics of Coronary Artery Disease

This aspect of my research involves studying genes related to coronary artery disease (CAD). It includes genetic epidemiological studies of how genes influence plasma risk factors such as lipid levels and blood coagulation factors, as well as clinical outcome such as atherosclerosis.

In the process of studying the genes, we have also built up a sizable database of about 3000 CAD and healthy individuals with information on more than 32 genotypes, environmental risk factors and family/medical histories. We have capitalized on this by developing an algorithm with the help of statisticians to predict CAD risk. The algorithm has since been patented and we are now validating it with more test cases.

The ultimate aim of our research is to be able to assess an individual’s risk of heart disease through family history, biochemical factors and genetic tests, especially for the neonates, so that preventive measures can be implemented early in life in order to delay the occurrence of CAD significantly or prevent it from occurring altogether.

Recently, we have also conducted some studies in the mouse and human cell line models to elucidate molecular mechanisms involved in dietary and acute phase protein responses.

II. Development of Lab-on-a-Chip Devices for biomedical applications

Another aspect of my research is in the development of biochips or “Lab-on-a-Chip” (LOC) devices for use in molecular diagnostics. LOC basically serves to miniaturize all the functions of regular bench-top equipments in the laboratory onto a chip no larger than the size of a credit card. We have successfully developed silicon biochips that can automatically extract nucleic acids (DNA or RNA) from blood. In essence, at the push of a button, blood goes into the chip and out comes pure DNA or RNA for carrying out genetic testing after about 1 hour. This breakthrough was made possible by combining the expertise from a highly dynamic team of engineers and biologists. There are three key advantages of LOC over conventional methods. These include i) Portability - the ability to be used at point-of-care or anywhere without the need to send samples to the laboratory, ii) Full Automation - does not require skilled operator, iii) Small Reaction Volume - thereby reducing reagent cost. Coupled with another of our invention, the microPCR for DNA amplification and other commercially available portable detection systems, the full capability of the LOC could be realized. We believe there is tremendous potential of our invention in shaping the way genetic tests are going to be carried out in the near future in diverse fields such as clinical, veterinary, forensic and medicine; agriculture; animal husbandry and biodefence.

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CK