I have often seen milk thistle (silymarin) touted as a shining star among natural remedies for hepatoprotective benefits. And although still controversial, it is intriguing to learn of its antiperoxidative effects in achieving small increases in glutathione levels (1).
No doubt that a 2008 meta-analysis from Switzerland on silymarin will pique your interest further. After reviewing the only 19 available "double-blind" and "single-blind" studies, no evidence was found to help with viral hepatitis, but in liver cirrhosis sylimarin was able to reduce aspartate aminotransferase, although not alkaline phosphatase (2)--this means it may help protect hepatocytes (liver cells).
The meta-analysis concluded that not enough clinical evidence existed for proper recommendation (2). But risk/benefit analysis would suggest it's reasonable to use sylimarin as a therapy for poisoning and may have minor benefit in liver cirrhosis (2).
References
1. Lucena MI, Andrade RJ, de la Cruz JP, Rodriguez-Mendizabal M, Blanco E, Sánchez de la Cuesta F. Effects of silymarin MZ-80 on oxidative stress in patients with alcoholic cirrhosis. Results of a randomized, double-blind, placebo-controlled clinical study. Int J Clin Pharmacol Ther. 2002 Jan;40(1):2-8.
2. Saller R, Brignoli R, Melzer J, Meier R..An updated systematic review with meta-analysis for the clinical evidence of silymarin. Forsch Komplementmed. 2008 Feb;15(1):9-20.
Sunday, June 28, 2009
Sliding filament model
What is troponin and what is its diagnostic value?
Troponin is a three-subunit protein complex that regulates striated (skeletal and cardiac) muscle contraction (1-3). Similar to caldesmon in smooth muscle, troponin affects release from actin (3). The process of muscle contraction is best represented by the sliding filament model (3). The model illustrates heavy dependence on calcium regulation for velocity involving “loose coupling” of calcium binding to troponin to determine the rate of “cycling cross-bridges” (4-6).
Cross-bridge cycling is a two-feedback mechanism—positive and negative—depending on its activation and regulation (6). Troponin subunit Tn-T is attached to tropomyocin is attached to actin (3). When a signal transmitted to the sarcoplasmic reticulum induces release of Ca(2+) into the sarcomere, then the Ca(2+) binds to subunit Tn-C, which changes orientation of subunit Tn-I (3). The Tn-I change causes a rotation in which the structure of tropomyosin rotates actin and exposes it to myosin binding sites creating contractibility (3). This action is critical in the heart (1). It’s worth noting that any mutations of cardiac troponin would affect this process, which develops cardiomyopathies (1;7). Contraction is stopped by ATPase pumping Ca(2+) out of the sarcomere furiously (3). Once in the sarcoplastmic reticulum, the Ca(2+) is taken away by calsequestrin (3).
As a diagnostic tool for myocardial infarction, troponins are highly valued because they can detect the smallest of infarctions in comparison to other cardiac markers such as electrocardiogram, creatine kinase (CK) and CK-MB (2). Tn-T can be expressed from skeletal muscle, but Tn-I is specific to myocardium (1). Any elevation of cardiac troponins are serious markers that largely indicate a poor prognosis with unstable angina (2).
Reference List
1. Biesiadecki BJ, Kobayashi T, Walker JS, John SR, de Tombe PP. The troponin C G159D mutation blunts myofilament desensitization induced by troponin I Ser23/24 phosphorylation. Circ Res 2007;100:1486-93.
2. Gaw A, Murphy MJ, Cowan RA, O'Reilly DStJ, Stewart MJ, Shepherd J. Clinical Biochemistry: An Illustrated Colour Text. Edinburgh: Churchill Livingstone Elsevier, 2008.
3. Devlin TM. Textbook of Biochemistry with Clinical Correlations. Philadelphia: Wiley-Liss, 2002.
4. Homsher E, Kim B, Bobkova A, Tobacman LS. Calcium regulation of thin filament movement in an in vitro motility assay. Biophys J 1996;70:1881-92.
5. Sata M, Yamashita H, Sugiura S, Fujita H, Momomura S, Serizawa T. A new in vitro motility assay technique to evaluate calcium sensitivity of the cardiac contractile proteins. Pflugers Arch 1995;429:443-5.
6. Landesberg A, Sideman S. Mechanical regulation of cardiac muscle by coupling calcium kinetics with cross-bridge cycling: a dynamic model. Am J Physiol 1994;267:H779-H795.
7. Lin D, Bobkova A, Homsher E, Tobacman LS. Altered cardiac troponin T in vitro function in the presence of a mutation implicated in familial hypertrophic cardiomyopathy. J Clin Invest 1996;97:2842-8.
8. Unverir P, Soner BC, Dedeoglu E, Karcioglu O, Boztok K, Tuncok Y. Renal and hepatic injury with elevated cardiac enzymes in Amanita phalloides poisoning: a case report. Hum Exp Toxicol 2007;26:757-61.
9. Livingston JC, Mabie BC, Ramanathan J. Crack cocaine, myocardial infarction, and troponin I levels at the time of cesarean delivery. Anesth Analg 2000;91:913-5, table.
Troponin is a three-subunit protein complex that regulates striated (skeletal and cardiac) muscle contraction (1-3). Similar to caldesmon in smooth muscle, troponin affects release from actin (3). The process of muscle contraction is best represented by the sliding filament model (3). The model illustrates heavy dependence on calcium regulation for velocity involving “loose coupling” of calcium binding to troponin to determine the rate of “cycling cross-bridges” (4-6).
Cross-bridge cycling is a two-feedback mechanism—positive and negative—depending on its activation and regulation (6). Troponin subunit Tn-T is attached to tropomyocin is attached to actin (3). When a signal transmitted to the sarcoplasmic reticulum induces release of Ca(2+) into the sarcomere, then the Ca(2+) binds to subunit Tn-C, which changes orientation of subunit Tn-I (3). The Tn-I change causes a rotation in which the structure of tropomyosin rotates actin and exposes it to myosin binding sites creating contractibility (3). This action is critical in the heart (1). It’s worth noting that any mutations of cardiac troponin would affect this process, which develops cardiomyopathies (1;7). Contraction is stopped by ATPase pumping Ca(2+) out of the sarcomere furiously (3). Once in the sarcoplastmic reticulum, the Ca(2+) is taken away by calsequestrin (3).
As a diagnostic tool for myocardial infarction, troponins are highly valued because they can detect the smallest of infarctions in comparison to other cardiac markers such as electrocardiogram, creatine kinase (CK) and CK-MB (2). Tn-T can be expressed from skeletal muscle, but Tn-I is specific to myocardium (1). Any elevation of cardiac troponins are serious markers that largely indicate a poor prognosis with unstable angina (2).
Reference List
1. Biesiadecki BJ, Kobayashi T, Walker JS, John SR, de Tombe PP. The troponin C G159D mutation blunts myofilament desensitization induced by troponin I Ser23/24 phosphorylation. Circ Res 2007;100:1486-93.
2. Gaw A, Murphy MJ, Cowan RA, O'Reilly DStJ, Stewart MJ, Shepherd J. Clinical Biochemistry: An Illustrated Colour Text. Edinburgh: Churchill Livingstone Elsevier, 2008.
3. Devlin TM. Textbook of Biochemistry with Clinical Correlations. Philadelphia: Wiley-Liss, 2002.
4. Homsher E, Kim B, Bobkova A, Tobacman LS. Calcium regulation of thin filament movement in an in vitro motility assay. Biophys J 1996;70:1881-92.
5. Sata M, Yamashita H, Sugiura S, Fujita H, Momomura S, Serizawa T. A new in vitro motility assay technique to evaluate calcium sensitivity of the cardiac contractile proteins. Pflugers Arch 1995;429:443-5.
6. Landesberg A, Sideman S. Mechanical regulation of cardiac muscle by coupling calcium kinetics with cross-bridge cycling: a dynamic model. Am J Physiol 1994;267:H779-H795.
7. Lin D, Bobkova A, Homsher E, Tobacman LS. Altered cardiac troponin T in vitro function in the presence of a mutation implicated in familial hypertrophic cardiomyopathy. J Clin Invest 1996;97:2842-8.
8. Unverir P, Soner BC, Dedeoglu E, Karcioglu O, Boztok K, Tuncok Y. Renal and hepatic injury with elevated cardiac enzymes in Amanita phalloides poisoning: a case report. Hum Exp Toxicol 2007;26:757-61.
9. Livingston JC, Mabie BC, Ramanathan J. Crack cocaine, myocardial infarction, and troponin I levels at the time of cesarean delivery. Anesth Analg 2000;91:913-5, table.
Case Report: Mushroom Poison Gives Off Mixed Messages
Forty-two hours after ingesting an unknown mushroom, a 56-year-old man was admitted to a Turkish emergency department (1). Cardiac markers troponin I, creatine kinase (CK), CK-MB isoenzyme, and myoglobin were all elevated (1). The testing detected nothing less than myocardial infarction (2). This diagnosis, however, was not correct.
The clinicians noted in their report that despite the potentially confusing cardiac markers, the patient was diagnosed with hepatic and renal falure (1). This is because in cases of mushroom poisoning, “amatoxins” bind with “actin filaments within myocardiocytes or renal cells and/or its effects as circulating antitropin antibodies” causing the cardiac markers to become elevated (1).
The patient was treated with fluids, activated charcoal, antibiotics and silibinin (an active constituent of milk thistle) and improvement followed (1).
Reference List
1. Unverir P, Soner BC, Dedeoglu E, Karcioglu O, Boztok K, Tuncok Y. Renal and hepatic injury with elevated cardiac enzymes in Amanita phalloides poisoning: a case report. Hum Exp Toxicol 2007;26:757-61.
2. Gaw A, Murphy MJ, Cowan RA, O'Reilly DStJ, Stewart MJ, Shepherd J. Clinical Biochemistry: An Illustrated Colour Text. Edinburgh: Churchill Livingstone Elsevier, 2008.
The clinicians noted in their report that despite the potentially confusing cardiac markers, the patient was diagnosed with hepatic and renal falure (1). This is because in cases of mushroom poisoning, “amatoxins” bind with “actin filaments within myocardiocytes or renal cells and/or its effects as circulating antitropin antibodies” causing the cardiac markers to become elevated (1).
The patient was treated with fluids, activated charcoal, antibiotics and silibinin (an active constituent of milk thistle) and improvement followed (1).
Reference List
1. Unverir P, Soner BC, Dedeoglu E, Karcioglu O, Boztok K, Tuncok Y. Renal and hepatic injury with elevated cardiac enzymes in Amanita phalloides poisoning: a case report. Hum Exp Toxicol 2007;26:757-61.
2. Gaw A, Murphy MJ, Cowan RA, O'Reilly DStJ, Stewart MJ, Shepherd J. Clinical Biochemistry: An Illustrated Colour Text. Edinburgh: Churchill Livingstone Elsevier, 2008.
Saturday, June 27, 2009
Fatty acids and Depression
Sailor Man Should Not Be Without His Olive
Omega-3 fatty acids from fish have largely stolen the spotlight for anti-depression, but recent evidence finds that oleic acid from olive oil may also be useful in women.
Last May a 10-year national cohort followed 1,947 men and 2,909 women (African-American and Caucasian) (1). They were separated according to “lowest, middle and highest” for oleic fatty acid intake as well as linoleic (omega-6) fatty acid intake (1). Estimates adjusted for fish consumption and diseases (1).
The researchers found linoleic acid was associated with increased risk of severe depression in men and that oleic acid (omega-9) was associated with a reduced risk of severe depression in women (1).
Popeye take note.
Depression, Gone Fishing
Stroll along the bank of river peacefully, bait your hook, cast, enjoy a beer. The fish themselves may not think so, but going fishing is a relaxing pastime. But don’t catch and release because eating those fish may even more of a mood booster. Well, that may be a stretch.
Truth is that a dietary deficiency of omega-3 fatty acids—found in amounts highest in fatty fish—may be related to great risk of depression, particularly among pregnant or menopausal women, according to recent studies (2-6).
Scientists have known for a while that an association between omega-3 fatty acids and depression exists, but it is still unclear why and its use as a single therapy has not been found to be effective; still researchers hope omega-3 oils can be used as complementary nutritional therapy to other treatments (2;7-10).
In fact, omega-3 was reconfirmed earlier this month by the Emory University School of Medicine to have a place as in researching emerging targets for antidepressant therapies (11;12). This is in light of frustration of failure of current treatments of depression drugs such as monoamine reuptake inhibitors and nutritional interventions to provide results (7;12).
Reference List
1. Wolfe AR, Ogbonna EM, Lim S, Li Y, Zhang J. Dietary linoleic and oleic fatty acids in relation to severe depressed mood: 10 years follow-up of a national cohort. Prog Neuropsychopharmacol Biol Psychiatry 2009.
2. Hazell P. Depression in children and adolescents. Clin Evid (Online ) 2009;2009.
3. Golding J, Steer C, Emmett P, Davis JM, Hibbeln JR. High levels of depressive symptoms in pregnancy with low omega-3 fatty acid intake from fish. Epidemiology 2009;20:598-603.
4. Rees AM, Austin MP, Owen C, Parker G. Omega-3 deficiency associated with perinatal depression: case control study. Psychiatry Res 2009;166:254-9.
5. Hibbeln JR. Depression, suicide and deficiencies of omega-3 essential fatty acids in modern diets. World Rev Nutr Diet 2009;99:17-30.
6. Lucas M, Asselin G, Merette C, Poulin MJ, Dodin S. Ethyl-eicosapentaenoic acid for the treatment of psychological distress and depressive symptoms in middle-aged women: a double-blind, placebo-controlled, randomized clinical trial. Am J Clin Nutr 2009;89:641-51.
7. Sarris J, Schoendorfer N, Kavanagh DJ. Major depressive disorder and nutritional medicine: a review of monotherapies and adjuvant treatments. Nutr Rev 2009;67:125-31.
8. Colangelo LA, He K, Whooley MA, Daviglus ML, Liu K. Higher dietary intake of long-chain omega-3 polyunsaturated fatty acids is inversely associated with depressive symptoms in women. Nutrition 2009.
9. Su KP. Biological mechanism of antidepressant effect of omega-3 fatty acids: how does fish oil act as a 'mind-body interface'? Neurosignals 2009;17:144-52.
10. Ramakrishnan U, Imhoff-Kunsch B, DiGirolamo AM. Role of docosahexaenoic acid in maternal and child mental health. Am J Clin Nutr 2009;89:958S-62S.
11. Rakofsky JJ, Holtzheimer PE, Nemeroff CB. Emerging targets for antidepressant therapies. Curr Opin Chem Biol 2009.
12. Holtzheimer PE, Nemeroff CB. Novel targets for antidepressant therapies. Curr Psychiatry Rep 2008;10:465-73.
Omega-3 fatty acids from fish have largely stolen the spotlight for anti-depression, but recent evidence finds that oleic acid from olive oil may also be useful in women.
Last May a 10-year national cohort followed 1,947 men and 2,909 women (African-American and Caucasian) (1). They were separated according to “lowest, middle and highest” for oleic fatty acid intake as well as linoleic (omega-6) fatty acid intake (1). Estimates adjusted for fish consumption and diseases (1).
The researchers found linoleic acid was associated with increased risk of severe depression in men and that oleic acid (omega-9) was associated with a reduced risk of severe depression in women (1).
Popeye take note.
Depression, Gone Fishing
Stroll along the bank of river peacefully, bait your hook, cast, enjoy a beer. The fish themselves may not think so, but going fishing is a relaxing pastime. But don’t catch and release because eating those fish may even more of a mood booster. Well, that may be a stretch.
Truth is that a dietary deficiency of omega-3 fatty acids—found in amounts highest in fatty fish—may be related to great risk of depression, particularly among pregnant or menopausal women, according to recent studies (2-6).
Scientists have known for a while that an association between omega-3 fatty acids and depression exists, but it is still unclear why and its use as a single therapy has not been found to be effective; still researchers hope omega-3 oils can be used as complementary nutritional therapy to other treatments (2;7-10).
In fact, omega-3 was reconfirmed earlier this month by the Emory University School of Medicine to have a place as in researching emerging targets for antidepressant therapies (11;12). This is in light of frustration of failure of current treatments of depression drugs such as monoamine reuptake inhibitors and nutritional interventions to provide results (7;12).
Reference List
1. Wolfe AR, Ogbonna EM, Lim S, Li Y, Zhang J. Dietary linoleic and oleic fatty acids in relation to severe depressed mood: 10 years follow-up of a national cohort. Prog Neuropsychopharmacol Biol Psychiatry 2009.
2. Hazell P. Depression in children and adolescents. Clin Evid (Online ) 2009;2009.
3. Golding J, Steer C, Emmett P, Davis JM, Hibbeln JR. High levels of depressive symptoms in pregnancy with low omega-3 fatty acid intake from fish. Epidemiology 2009;20:598-603.
4. Rees AM, Austin MP, Owen C, Parker G. Omega-3 deficiency associated with perinatal depression: case control study. Psychiatry Res 2009;166:254-9.
5. Hibbeln JR. Depression, suicide and deficiencies of omega-3 essential fatty acids in modern diets. World Rev Nutr Diet 2009;99:17-30.
6. Lucas M, Asselin G, Merette C, Poulin MJ, Dodin S. Ethyl-eicosapentaenoic acid for the treatment of psychological distress and depressive symptoms in middle-aged women: a double-blind, placebo-controlled, randomized clinical trial. Am J Clin Nutr 2009;89:641-51.
7. Sarris J, Schoendorfer N, Kavanagh DJ. Major depressive disorder and nutritional medicine: a review of monotherapies and adjuvant treatments. Nutr Rev 2009;67:125-31.
8. Colangelo LA, He K, Whooley MA, Daviglus ML, Liu K. Higher dietary intake of long-chain omega-3 polyunsaturated fatty acids is inversely associated with depressive symptoms in women. Nutrition 2009.
9. Su KP. Biological mechanism of antidepressant effect of omega-3 fatty acids: how does fish oil act as a 'mind-body interface'? Neurosignals 2009;17:144-52.
10. Ramakrishnan U, Imhoff-Kunsch B, DiGirolamo AM. Role of docosahexaenoic acid in maternal and child mental health. Am J Clin Nutr 2009;89:958S-62S.
11. Rakofsky JJ, Holtzheimer PE, Nemeroff CB. Emerging targets for antidepressant therapies. Curr Opin Chem Biol 2009.
12. Holtzheimer PE, Nemeroff CB. Novel targets for antidepressant therapies. Curr Psychiatry Rep 2008;10:465-73.
Omega Ratio Rationale?
The plethora of scientific studies on lipids and nutrition would have nutritionists thinking within reason that omega-3s are the chosen fatty acid to deliver humankind from sickness. But despite the seemingly omnipotent oil’s overabundance of qualities, not nearly enough is known about how much to consume in relation to other fatty acids such as omega-6.
In June 2008, top cardiologists convened to examine all clinical evidence and discuss optimal omega-3 dosages (1). The conclusions were summarized with a recommendation of at least 250 mg of DHA and EPA fatty acids for the “primary prevention of cardiovascular disease” (1). No ratio recommendation was given, which was purposeful.
In fact, the focus on omega-3 to omega-6 ratios had been heavily criticized earlier. A report in 2007 by the UK Food Standards Agency said that “ratio is not a useful concept and it distracts attention away from absolute intakes” (2). And a year earlier, top American omega-3 fatty acid researcher William S. Harris, Ph.D., of University of South Dakota’s Nutrition and Metabolic Diseases Research Institute wrote that “although initially appealing” for making nutritional recommendations, ratio is “of little value” (3). Lacking clinical data, the UK Food Standards Agency, Dr Harris and others may be correct in calling for concentration solely on omega-3 for established treatment(4;5).
Many clinicians and researchers, however, continue to advise and perform studies from the theoretical viewpoint of a ratio. A microscopic view reveals answers to why. The function of omega-3 and omega-6 in the cell or an organ such as the liver or brain highlights key differences. Dr Harris does concede these facts: that the two fatty acids compete for enzymes and have opposite effects (3). In addition to omega-3’s anti-inflammatory and omega-6’s inflammatory uniqueness (6), the biochemistry also presents information on how each influences metabolism, genetic expression (6-10), cell membrane function and neurotransmission (6;11). While insightful, however, the information does stop short of any clinical parameters.
As a base for perspective, nutritionists find it useful to turn to dietary origins. Nutritional anthropology and epidemiological studies suggest a ratio of 1-2:1 omega-6 to omega-3, which is in large contrast to the typical Western diet of 15-16:1 (6;12-15). And many ratios resembling the ideal hunter-gatherer 1:1 do propose significant reduction of risk of chronic disease, mainly coronary artery disease and arthritis (6;15). These research approaches come with caution as they are not enough for science in absolute, nor do they offer indication of any exact amounts for best efficacy.
Truer data must come from well-designed randomized, double-blind controlled trials. To reflect proper indications, these studies should take into account ratio, amounts or both. An example of a trial was conducted in 2003 when two parallel groups of 15 patients who each had major elective abdominal surgery were given omega-6 to omega-3 ratio of 3:1, which confirmed a significant anti-inflammatory effect (16). More trials such as this one could illuminate further.
Reference List
1. Deckelbaum RJ, Leaf A, Mozaffarian D, Jacobson TA, Harris WS, Akabas SR. Conclusions and recommendations from the symposium, Beyond Cholesterol: Prevention and Treatment of Coronary Heart Disease with n-3 Fatty Acids. Am J Clin Nutr 2008;87:2010S-2S.
2. Stanley JC, Elsom RL, Calder PC et al. UK Food Standards Agency Workshop Report: the effects of the dietary n-6:n-3 fatty acid ratio on cardiovascular health. Br J Nutr 2007;98:1305-10.
3. Harris WS. The omega-6/omega-3 ratio and cardiovascular disease risk: uses and abuses. Curr Atheroscler Rep 2006;8:453-9.
4. Harris WS. Omega-3 fatty acids and cardiovascular disease: a case for omega-3 index as a new risk factor. Pharmacol Res 2007;55:217-23.
5. Harris WS, Assaad B, Poston WC. Tissue omega-6/omega-3 fatty acid ratio and risk for coronary artery disease. Am J Cardiol 2006;98:19i-26i.
6. Simopoulos AP. The omega-6/omega-3 fatty acid ratio, genetic variation, and cardiovascular disease. Asia Pac J Clin Nutr 2008;17 Suppl 1:131-4.
7. Kang JX. The importance of omega-6/omega-3 fatty acid ratio in cell function. The gene transfer of omega-3 fatty acid desaturase. World Rev Nutr Diet 2003;92:23-36.
8. Takeuchi H, Kojima K, Sekine S, Murano Y, Aoyama T. Effect of dietary n-6/n-3 ratio on liver n-6/n-3 ratio and peroxisomal beta-oxidation activity in rats. J Oleo Sci 2008;57:649-57.
9. Lu Y, Nie D, Witt WT et al. Expression of the fat-1 gene diminishes prostate cancer growth in vivo through enhancing apoptosis and inhibiting GSK-3 beta phosphorylation. Mol Cancer Ther 2008;7:3203-11.
10. El-Badry AM, Graf R, Clavien PA. Omega 3 - Omega 6: What is right for the liver? J Hepatol 2007;47:718-25.
11. Haag M. Essential fatty acids and the brain. Can J Psychiatry 2003;48:195-203.
12. Simopoulos AP. Evolutionary aspects of diet, the omega-6/omega-3 ratio and genetic variation: nutritional implications for chronic diseases. Biomed Pharmacother 2006;60:502-7.
13. Cordain L, Eaton SB, Sebastian A et al. Origins and evolution of the Western diet: health implications for the 21st century. Am J Clin Nutr 2005;81:341-54.
14. Simopoulos AP. The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp Biol Med (Maywood ) 2008;233:674-88.
15. Simopoulos AP. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother 2002;56:365-79.
16. Koller M, Senkal M, Kemen M, Konig W, Zumtobel V, Muhr G. Impact of omega-3 fatty acid enriched TPN on leukotriene synthesis by leukocytes after major surgery. Clin Nutr 2003;22:59-64.
In June 2008, top cardiologists convened to examine all clinical evidence and discuss optimal omega-3 dosages (1). The conclusions were summarized with a recommendation of at least 250 mg of DHA and EPA fatty acids for the “primary prevention of cardiovascular disease” (1). No ratio recommendation was given, which was purposeful.
In fact, the focus on omega-3 to omega-6 ratios had been heavily criticized earlier. A report in 2007 by the UK Food Standards Agency said that “ratio is not a useful concept and it distracts attention away from absolute intakes” (2). And a year earlier, top American omega-3 fatty acid researcher William S. Harris, Ph.D., of University of South Dakota’s Nutrition and Metabolic Diseases Research Institute wrote that “although initially appealing” for making nutritional recommendations, ratio is “of little value” (3). Lacking clinical data, the UK Food Standards Agency, Dr Harris and others may be correct in calling for concentration solely on omega-3 for established treatment(4;5).
Many clinicians and researchers, however, continue to advise and perform studies from the theoretical viewpoint of a ratio. A microscopic view reveals answers to why. The function of omega-3 and omega-6 in the cell or an organ such as the liver or brain highlights key differences. Dr Harris does concede these facts: that the two fatty acids compete for enzymes and have opposite effects (3). In addition to omega-3’s anti-inflammatory and omega-6’s inflammatory uniqueness (6), the biochemistry also presents information on how each influences metabolism, genetic expression (6-10), cell membrane function and neurotransmission (6;11). While insightful, however, the information does stop short of any clinical parameters.
As a base for perspective, nutritionists find it useful to turn to dietary origins. Nutritional anthropology and epidemiological studies suggest a ratio of 1-2:1 omega-6 to omega-3, which is in large contrast to the typical Western diet of 15-16:1 (6;12-15). And many ratios resembling the ideal hunter-gatherer 1:1 do propose significant reduction of risk of chronic disease, mainly coronary artery disease and arthritis (6;15). These research approaches come with caution as they are not enough for science in absolute, nor do they offer indication of any exact amounts for best efficacy.
Truer data must come from well-designed randomized, double-blind controlled trials. To reflect proper indications, these studies should take into account ratio, amounts or both. An example of a trial was conducted in 2003 when two parallel groups of 15 patients who each had major elective abdominal surgery were given omega-6 to omega-3 ratio of 3:1, which confirmed a significant anti-inflammatory effect (16). More trials such as this one could illuminate further.
Reference List
1. Deckelbaum RJ, Leaf A, Mozaffarian D, Jacobson TA, Harris WS, Akabas SR. Conclusions and recommendations from the symposium, Beyond Cholesterol: Prevention and Treatment of Coronary Heart Disease with n-3 Fatty Acids. Am J Clin Nutr 2008;87:2010S-2S.
2. Stanley JC, Elsom RL, Calder PC et al. UK Food Standards Agency Workshop Report: the effects of the dietary n-6:n-3 fatty acid ratio on cardiovascular health. Br J Nutr 2007;98:1305-10.
3. Harris WS. The omega-6/omega-3 ratio and cardiovascular disease risk: uses and abuses. Curr Atheroscler Rep 2006;8:453-9.
4. Harris WS. Omega-3 fatty acids and cardiovascular disease: a case for omega-3 index as a new risk factor. Pharmacol Res 2007;55:217-23.
5. Harris WS, Assaad B, Poston WC. Tissue omega-6/omega-3 fatty acid ratio and risk for coronary artery disease. Am J Cardiol 2006;98:19i-26i.
6. Simopoulos AP. The omega-6/omega-3 fatty acid ratio, genetic variation, and cardiovascular disease. Asia Pac J Clin Nutr 2008;17 Suppl 1:131-4.
7. Kang JX. The importance of omega-6/omega-3 fatty acid ratio in cell function. The gene transfer of omega-3 fatty acid desaturase. World Rev Nutr Diet 2003;92:23-36.
8. Takeuchi H, Kojima K, Sekine S, Murano Y, Aoyama T. Effect of dietary n-6/n-3 ratio on liver n-6/n-3 ratio and peroxisomal beta-oxidation activity in rats. J Oleo Sci 2008;57:649-57.
9. Lu Y, Nie D, Witt WT et al. Expression of the fat-1 gene diminishes prostate cancer growth in vivo through enhancing apoptosis and inhibiting GSK-3 beta phosphorylation. Mol Cancer Ther 2008;7:3203-11.
10. El-Badry AM, Graf R, Clavien PA. Omega 3 - Omega 6: What is right for the liver? J Hepatol 2007;47:718-25.
11. Haag M. Essential fatty acids and the brain. Can J Psychiatry 2003;48:195-203.
12. Simopoulos AP. Evolutionary aspects of diet, the omega-6/omega-3 ratio and genetic variation: nutritional implications for chronic diseases. Biomed Pharmacother 2006;60:502-7.
13. Cordain L, Eaton SB, Sebastian A et al. Origins and evolution of the Western diet: health implications for the 21st century. Am J Clin Nutr 2005;81:341-54.
14. Simopoulos AP. The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp Biol Med (Maywood ) 2008;233:674-88.
15. Simopoulos AP. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother 2002;56:365-79.
16. Koller M, Senkal M, Kemen M, Konig W, Zumtobel V, Muhr G. Impact of omega-3 fatty acid enriched TPN on leukotriene synthesis by leukocytes after major surgery. Clin Nutr 2003;22:59-64.
Sunday, June 21, 2009
Acute Tubular Necrosis and Glomerulonephritis
Acute tubular necrosis (ATN) is a condition resulting from tubular cell apoptosis contributing to renal failure (1-3). It can result due to insult from extensive injury such as acute blood loss or septic shock, a specific renal disease such as glomerulonephritis, nephrotoxic drugs or bacterial products, or hypoxia (1-3).
ATN is identified via a rising serum urea creatinine and can be classified as pre-renal, renal or post-renal (1). If identified early, corrective action can stop damage and possible hyperkalemia (1).
Managing ATN includes caring for patient by replacing extra cellular fluid when necessary, controlling an underlying infection that may be cause, monitoring body fluid volume closely and via dialysis (1). Recovery involves three phases: initial oliguric phase (impairment), diuretic phase (high-urine output) and recovery phase (return of complete renal function) (1).
Glomerulonephritis is an inflammation of the glomeruli, which causes progressive renal damage that can lead to ATN and renal failure (4-6). The disease is mainly caused by infection such as streptococcal infection (7;8). In post-streptococcal glomerulonephritis, symptoms can include sudden hypertension, proteinuria, edema and hematuria (9). The inflammatory response causing the damage to the kidneys is thought to be related to hypersensitive immune response (9). Maintenance generally can include treatment of underlying disease, balancing electrolytes and fluids, and possible peritoneal dialysis (10).
Reference List
1. Gaw A, Murphy MJ, Cowan RA, O'Reilly DStJ, Stewart MJ, Shepherd J. Clinical Biochemistry: An Illustrated Colour Text. Edinburgh: Churchill Livingstone Elsevier, 2008.
2. Rosen S, Stillman IE. Acute tubular necrosis is a syndrome of physiologic and pathologic dissociation. J Am Soc Nephrol 2008;19:871-5.
3. Ortiz A, Justo P, Sanz A, Lorz C, Egido J. Targeting apoptosis in acute tubular injury. Biochem Pharmacol 2003;66:1589-94.
4. Vinen CS, Oliveira DB. Acute glomerulonephritis. Postgrad Med J 2003;79:206-13.
5. Feith GW, Assmann KJ, Wetzels JF. Acute renal failure in patients with glomerular diseases: a consequence of tubular cell damage caused by haematuria? Neth J Med 2003;61:146-50.
6. Ruiz P, Soares MF. Acute postinfectious glomerulonephritis: an immune response gone bad? Hum Pathol 2003;34:1-2.
7. Prakash J, Sen D, Kumar NS, Kumar H, Tripathi LK, Saxena RK. Acute renal failure due to intrinsic renal diseases: review of 1122 cases. Ren Fail 2003;25:225-33.
8. Faurie RE, Prado AC. [Streptococcal infection, acute kidney failure and interstitial nephritis]. Medicina (B Aires) 2000;60:953-5.
9. Yoshizawa N. Acute glomerulonephritis. Intern Med 2000;39:687-94.
10. Filler G. Acute renal failure in children: aetiology and management. Paediatr Drugs 2001;3:783-92.
ATN is identified via a rising serum urea creatinine and can be classified as pre-renal, renal or post-renal (1). If identified early, corrective action can stop damage and possible hyperkalemia (1).
Managing ATN includes caring for patient by replacing extra cellular fluid when necessary, controlling an underlying infection that may be cause, monitoring body fluid volume closely and via dialysis (1). Recovery involves three phases: initial oliguric phase (impairment), diuretic phase (high-urine output) and recovery phase (return of complete renal function) (1).
Glomerulonephritis is an inflammation of the glomeruli, which causes progressive renal damage that can lead to ATN and renal failure (4-6). The disease is mainly caused by infection such as streptococcal infection (7;8). In post-streptococcal glomerulonephritis, symptoms can include sudden hypertension, proteinuria, edema and hematuria (9). The inflammatory response causing the damage to the kidneys is thought to be related to hypersensitive immune response (9). Maintenance generally can include treatment of underlying disease, balancing electrolytes and fluids, and possible peritoneal dialysis (10).
Reference List
1. Gaw A, Murphy MJ, Cowan RA, O'Reilly DStJ, Stewart MJ, Shepherd J. Clinical Biochemistry: An Illustrated Colour Text. Edinburgh: Churchill Livingstone Elsevier, 2008.
2. Rosen S, Stillman IE. Acute tubular necrosis is a syndrome of physiologic and pathologic dissociation. J Am Soc Nephrol 2008;19:871-5.
3. Ortiz A, Justo P, Sanz A, Lorz C, Egido J. Targeting apoptosis in acute tubular injury. Biochem Pharmacol 2003;66:1589-94.
4. Vinen CS, Oliveira DB. Acute glomerulonephritis. Postgrad Med J 2003;79:206-13.
5. Feith GW, Assmann KJ, Wetzels JF. Acute renal failure in patients with glomerular diseases: a consequence of tubular cell damage caused by haematuria? Neth J Med 2003;61:146-50.
6. Ruiz P, Soares MF. Acute postinfectious glomerulonephritis: an immune response gone bad? Hum Pathol 2003;34:1-2.
7. Prakash J, Sen D, Kumar NS, Kumar H, Tripathi LK, Saxena RK. Acute renal failure due to intrinsic renal diseases: review of 1122 cases. Ren Fail 2003;25:225-33.
8. Faurie RE, Prado AC. [Streptococcal infection, acute kidney failure and interstitial nephritis]. Medicina (B Aires) 2000;60:953-5.
9. Yoshizawa N. Acute glomerulonephritis. Intern Med 2000;39:687-94.
10. Filler G. Acute renal failure in children: aetiology and management. Paediatr Drugs 2001;3:783-92.
How does alcohol affect kidney function?
What effects do you think alcohol consumption could have on renal function tests?
You’ve heard before that alcohol in moderation (in moderation!) may be good for your heart, but what can it do to your kidneys? Acute and chronic alcohol consumption does alter renal function and other physiological processes such as blood flow and fluid and electrolyte balances, which can directly affect results of renal function tests (1;2). Effects include higher level of creatine clearance and glomerular filtration rate (3). The alterations are especially noticeable in cases of liver disease (1;2).
Heavy drinking—which would be four or more alcoholic drinks a day—has a strong correlation with chronic kidney disease, especially in patients who smoke, have diabetes or hypertension or who are obese (4). When under condition of liver cirrhosis, chronic alcohol intake has been shown in rats and humans to possibly play a role in causing kidney enlargement and alterations in tubules (1). This all suggests renal detriment from consumption of alcohol.
However, prospective cohorts on moderate consumption in men and women tell a different story. A 2005 study on 11,023 healthy men over 14 years found that while there was association between alcohol consumption and glomerular filtration rates, moderate alcohol consumption actually caused a lower risk of renal dysfunction over time (5). A 2005 study on 1,658 female nurses for 11 years showed similar data in that while glomerular filtration rate was affected, moederate alcohol consumption had no adverse effect on renal dysfunction over time (2).
Good news for moderate drinkers!
Reference List
1. Epstein M. Alcohol's impact on kidney function. Alcohol Health Res World 1997;21:84-92.
2. Knight EL, Stampfer MJ, Rimm EB, Hankinson SE, Curhan GC. Moderate alcohol intake and renal function decline in women: a prospective study. Nephrol Dial Transplant 2003;18:1549-54.
3. Chung FM, Yang YH, Shieh TY, Shin SJ, Tsai JC, Lee YJ. Effect of alcohol consumption on estimated glomerular filtration rate and creatinine clearance rate. Nephrol Dial Transplant 2005;20:1610-6.
4. Shankar A, Klein R, Klein BE. The association among smoking, heavy drinking, and chronic kidney disease. Am J Epidemiol 2006;164:263-71.
5. Schaeffner ES, Kurth T, de Jong PE, Glynn RJ, Buring JE, Gaziano JM. Alcohol consumption and the risk of renal dysfunction in apparently healthy men. Arch Intern Med 2005;165:1048-53.
You’ve heard before that alcohol in moderation (in moderation!) may be good for your heart, but what can it do to your kidneys? Acute and chronic alcohol consumption does alter renal function and other physiological processes such as blood flow and fluid and electrolyte balances, which can directly affect results of renal function tests (1;2). Effects include higher level of creatine clearance and glomerular filtration rate (3). The alterations are especially noticeable in cases of liver disease (1;2).
Heavy drinking—which would be four or more alcoholic drinks a day—has a strong correlation with chronic kidney disease, especially in patients who smoke, have diabetes or hypertension or who are obese (4). When under condition of liver cirrhosis, chronic alcohol intake has been shown in rats and humans to possibly play a role in causing kidney enlargement and alterations in tubules (1). This all suggests renal detriment from consumption of alcohol.
However, prospective cohorts on moderate consumption in men and women tell a different story. A 2005 study on 11,023 healthy men over 14 years found that while there was association between alcohol consumption and glomerular filtration rates, moderate alcohol consumption actually caused a lower risk of renal dysfunction over time (5). A 2005 study on 1,658 female nurses for 11 years showed similar data in that while glomerular filtration rate was affected, moederate alcohol consumption had no adverse effect on renal dysfunction over time (2).
Good news for moderate drinkers!
Reference List
1. Epstein M. Alcohol's impact on kidney function. Alcohol Health Res World 1997;21:84-92.
2. Knight EL, Stampfer MJ, Rimm EB, Hankinson SE, Curhan GC. Moderate alcohol intake and renal function decline in women: a prospective study. Nephrol Dial Transplant 2003;18:1549-54.
3. Chung FM, Yang YH, Shieh TY, Shin SJ, Tsai JC, Lee YJ. Effect of alcohol consumption on estimated glomerular filtration rate and creatinine clearance rate. Nephrol Dial Transplant 2005;20:1610-6.
4. Shankar A, Klein R, Klein BE. The association among smoking, heavy drinking, and chronic kidney disease. Am J Epidemiol 2006;164:263-71.
5. Schaeffner ES, Kurth T, de Jong PE, Glynn RJ, Buring JE, Gaziano JM. Alcohol consumption and the risk of renal dysfunction in apparently healthy men. Arch Intern Med 2005;165:1048-53.
Why 24-hr urine test isn't enough
Why isn’t a total urine volume taken over 24 hours enough to assess renal function?
A total 24-hour urine volume can be useful for identifying reduced or increased urine volume, but it is unreliable (not to mention inconvenient) and still not enough to identify renal dysfunction or failure (it can simply indicate dehydration, high fluid intake or use of diuretics) (1-3).
The measurement of urinary excretion of creatinine of the 24-hour urine volume, called creatinine clearance, reveals more because it can better indicate glomerular filtration rate (GFR) (1;2). However, creatine clearance is still limited in its precision due to possible confounding variables (1).
An approach to support proper investigation into renal function should include other measures inclindin estimated GFR (considering age, sex, ethinicity and weight) as well as tests for other markers of clearance such as cystatin C (a protein almost unaffected by meat intake), inulin (most accurate estimate of GFR) and albumin (indicator of proteinuria) (1).
Apart from GFR, in cases of possible renal tubular dysfunction measurement of tubular reabsorption is necessary because it may contribute to acute renal failure (1). Usually tubular damage occurs due to other conditions (1). Examination may include osmolality measurements of plasma and urine, water deprivation tests, urine pH and acid load tests, specific proteinuria, aminoaciduria or glycosuria tests (1).
Reference List
1. Gaw A, Murphy MJ, Cowan RA, O'Reilly DStJ, Stewart MJ, Shepherd J. Clinical Biochemistry: An Illustrated Colour Text. Edinburgh: Churchill Livingstone Elsevier, 2008.
2. Adebisi SA, Adekunle BA, Etu AK. Creatinine clearance: alternative approach to traditional 24-hour urine collection in normal individuals. Afr J Med Med Sci 2001;30:27-30.
3. MedlinePlus. Urine 24-hour volume. Medical Encyclopedia. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/003425.htm. Accessed on 21 June 2009.
A total 24-hour urine volume can be useful for identifying reduced or increased urine volume, but it is unreliable (not to mention inconvenient) and still not enough to identify renal dysfunction or failure (it can simply indicate dehydration, high fluid intake or use of diuretics) (1-3).
The measurement of urinary excretion of creatinine of the 24-hour urine volume, called creatinine clearance, reveals more because it can better indicate glomerular filtration rate (GFR) (1;2). However, creatine clearance is still limited in its precision due to possible confounding variables (1).
An approach to support proper investigation into renal function should include other measures inclindin estimated GFR (considering age, sex, ethinicity and weight) as well as tests for other markers of clearance such as cystatin C (a protein almost unaffected by meat intake), inulin (most accurate estimate of GFR) and albumin (indicator of proteinuria) (1).
Apart from GFR, in cases of possible renal tubular dysfunction measurement of tubular reabsorption is necessary because it may contribute to acute renal failure (1). Usually tubular damage occurs due to other conditions (1). Examination may include osmolality measurements of plasma and urine, water deprivation tests, urine pH and acid load tests, specific proteinuria, aminoaciduria or glycosuria tests (1).
Reference List
1. Gaw A, Murphy MJ, Cowan RA, O'Reilly DStJ, Stewart MJ, Shepherd J. Clinical Biochemistry: An Illustrated Colour Text. Edinburgh: Churchill Livingstone Elsevier, 2008.
2. Adebisi SA, Adekunle BA, Etu AK. Creatinine clearance: alternative approach to traditional 24-hour urine collection in normal individuals. Afr J Med Med Sci 2001;30:27-30.
3. MedlinePlus. Urine 24-hour volume. Medical Encyclopedia. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/003425.htm. Accessed on 21 June 2009.
Wednesday, June 17, 2009
Fiber for IBS, which is best?
Patients with irritable bowel syndrome (IBS) could find great relief from using dietary fiber, but how can clinicians make sure they get the right fiber?
A 2004 systemic review published in Ailment Pharmacol Ther improved means of advising patients with IBS on which fiber to take. The review included 17 randomized, controlled trials on both soluble (psyillium, ispaghula, calcium polycarbophil) and insoluble fiber sources (corn and wheat bran) (1). The researchers found that the soluble fiber sources were effective in providing relief to patients while insoluble fiber sources worsened symptoms in a few cases (1).
Based on these important findings, the Harvard University Medical School advised that soluble sources of fiber “are more effective” than that of insoluble for IBS in “alleviating global symptoms and relieving constipation, although fiber in general has marginal benefit” (2).
Reference List
1. Bijkerk CJ, Muris JW, Knottnerus JA, Hoes AW, de Wit NJ. Systematic review: the role of different types of fibre in the treatment of irritable bowel syndrome. Aliment Pharmacol Ther 2004;19:245-51.
2. Chang HY, Kelly EC, Lembo AJ. Current gut-directed therapies for irritable bowel syndrome. Curr Treat Options Gastroenterol 2006;9:314-23.
A 2004 systemic review published in Ailment Pharmacol Ther improved means of advising patients with IBS on which fiber to take. The review included 17 randomized, controlled trials on both soluble (psyillium, ispaghula, calcium polycarbophil) and insoluble fiber sources (corn and wheat bran) (1). The researchers found that the soluble fiber sources were effective in providing relief to patients while insoluble fiber sources worsened symptoms in a few cases (1).
Based on these important findings, the Harvard University Medical School advised that soluble sources of fiber “are more effective” than that of insoluble for IBS in “alleviating global symptoms and relieving constipation, although fiber in general has marginal benefit” (2).
Reference List
1. Bijkerk CJ, Muris JW, Knottnerus JA, Hoes AW, de Wit NJ. Systematic review: the role of different types of fibre in the treatment of irritable bowel syndrome. Aliment Pharmacol Ther 2004;19:245-51.
2. Chang HY, Kelly EC, Lembo AJ. Current gut-directed therapies for irritable bowel syndrome. Curr Treat Options Gastroenterol 2006;9:314-23.
Tuesday, June 16, 2009
Is Metabolic Syndrome for real or just a popular clinical tool?
Cardiovascular disease and diabetes have several inter-related risk factors that may include obesity, high-cholesterol, high-triglycerides, hypertension, insulin resistance and inflammation (1). All these separate conditions can be treated in various ways. But why not lump them all together: metabolic syndrome?
Combining the cluster of risk factors into one condition remains controversial among scientists. On one side of the coin are those that metabolic syndrome provides a greater perspective for treating and managing reduction of all factors to avoid future problems (1;2). On the other side of the coin are those who find that evidence is not reliable enough and that more work is needed before risk factors can be chosen before defining metabolic syndrome as a clinical tool (3-6).
Clinicians, however, can rest assured that while research should continue into metabolic syndrome, the current definition of the condition can be helpful. According to a systemic review and meta-analysis published in 2007 by Mayo Clinic on 43 cohorts, there was a strong association of “increased risk of cardiovascular events” with those with metabolic syndrome (7). Thus, ultimately, the most recent data suggest that using metabolic syndrome as a clinical tool for treating and counseling patients shows great promise.
Reference List
1. Lien LF, Guyton JR. Metabolic syndrome. Dermatol Ther 2008;21:362-75.
2. Gallagher EJ, LeRoith D, Karnieli E. The metabolic syndrome--from insulin resistance to obesity and diabetes. Endocrinol Metab Clin North Am 2008;37:559-79, vii.
3. Schweiger C, Cirrincione V, Ignone G. [Metabolic syndrome: a true syndrome or only a cluster of risk factors?]. G Ital Cardiol (Rome) 2008;9:67S-73S.
4. Balkau B, Valensi P, Eschwege E, Slama G. A review of the metabolic syndrome. Diabetes Metab 2007;33:405-13.
5. Brietzke SA. Controversy in diagnosis and management of the metabolic syndrome. Med Clin North Am 2007;91:1041-viii.
6. Cheng AY, Leiter LA. Metabolic syndrome under fire: weighing in on the truth. Can J Cardiol 2006;22:379-82.
7. Gami AS, Witt BJ, Howard DE et al. Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies. J Am Coll Cardiol 2007;49:403-14.
Combining the cluster of risk factors into one condition remains controversial among scientists. On one side of the coin are those that metabolic syndrome provides a greater perspective for treating and managing reduction of all factors to avoid future problems (1;2). On the other side of the coin are those who find that evidence is not reliable enough and that more work is needed before risk factors can be chosen before defining metabolic syndrome as a clinical tool (3-6).
Clinicians, however, can rest assured that while research should continue into metabolic syndrome, the current definition of the condition can be helpful. According to a systemic review and meta-analysis published in 2007 by Mayo Clinic on 43 cohorts, there was a strong association of “increased risk of cardiovascular events” with those with metabolic syndrome (7). Thus, ultimately, the most recent data suggest that using metabolic syndrome as a clinical tool for treating and counseling patients shows great promise.
Reference List
1. Lien LF, Guyton JR. Metabolic syndrome. Dermatol Ther 2008;21:362-75.
2. Gallagher EJ, LeRoith D, Karnieli E. The metabolic syndrome--from insulin resistance to obesity and diabetes. Endocrinol Metab Clin North Am 2008;37:559-79, vii.
3. Schweiger C, Cirrincione V, Ignone G. [Metabolic syndrome: a true syndrome or only a cluster of risk factors?]. G Ital Cardiol (Rome) 2008;9:67S-73S.
4. Balkau B, Valensi P, Eschwege E, Slama G. A review of the metabolic syndrome. Diabetes Metab 2007;33:405-13.
5. Brietzke SA. Controversy in diagnosis and management of the metabolic syndrome. Med Clin North Am 2007;91:1041-viii.
6. Cheng AY, Leiter LA. Metabolic syndrome under fire: weighing in on the truth. Can J Cardiol 2006;22:379-82.
7. Gami AS, Witt BJ, Howard DE et al. Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies. J Am Coll Cardiol 2007;49:403-14.
Monday, June 15, 2009
Search for Diabetic Snacks Means “High in Fiber”
Who wouldn’t want a biscuit? Not a diabetic or anyone else fearing a high-glycemic response. Not more than one or two at least. But will a patented, highly viscous fiber blend change how we enjoy starchy-tasting snacks?
Croatian food scientists who have been studying the fiber blend reported that, when included as an ingredient in biscuits, it was successful in maintaining healthy blood sugar levels (1). The researchers tested the fiber biscuits on a small number of healthy and diabetic participants in a small randomized, controlled, single-blind, four-arm crossover trial published in 2008 (1).
The biscuits included 10 grams of the fiber blend and 50 grams of carbohydrates. They were compared in the study to 50-gram carbohydrate biscuits alone, white bread alone containing 66.8 grams of white flour, and of white bread with 12 grams of margarine (1).
Each participant was given each treatment after a 12-hour overnight fast (1). Finger-prick blood samples were then taken in four 15-minute intervals and one after 90 minutes (1). At least three days occurred between testing sessions (1).
The testing confirmed that there was no difference in palatability from including the fiber blend in the biscuits, but that gastric emptying was delayed effectively lowering the glycemic response of the biscuits significantly (1). In contrast, the 12 grams of margarine on the white bread had no effect on glycemic response (1).
The study reported that the results suggest the fiber blend could be used to “replace fiber depleted high fat snack foods” (1). The low-glycemic index snacks would then meet the needs of those with type 2 diabetes mellitus and those with cardiovascular disease (1).
The fiber blend was reported to be more effective in lowering glycemic response than other soluble fibers including psyllium hulls, glucomannan alone, beta-glucan, guar gum, pectin and ground flax seed (1).
Reference List
1. Jenkins AL, Jenkins DJ, Wolever TM et al. Comparable postprandial glucose reductions with viscous fiber blend enriched biscuits in healthy subjects and patients with diabetes mellitus: acute randomized controlled clinical trial. Croat Med J 2008;49:772-82. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=19090602. Accessed on 15 June 2009.
Croatian food scientists who have been studying the fiber blend reported that, when included as an ingredient in biscuits, it was successful in maintaining healthy blood sugar levels (1). The researchers tested the fiber biscuits on a small number of healthy and diabetic participants in a small randomized, controlled, single-blind, four-arm crossover trial published in 2008 (1).
The biscuits included 10 grams of the fiber blend and 50 grams of carbohydrates. They were compared in the study to 50-gram carbohydrate biscuits alone, white bread alone containing 66.8 grams of white flour, and of white bread with 12 grams of margarine (1).
Each participant was given each treatment after a 12-hour overnight fast (1). Finger-prick blood samples were then taken in four 15-minute intervals and one after 90 minutes (1). At least three days occurred between testing sessions (1).
The testing confirmed that there was no difference in palatability from including the fiber blend in the biscuits, but that gastric emptying was delayed effectively lowering the glycemic response of the biscuits significantly (1). In contrast, the 12 grams of margarine on the white bread had no effect on glycemic response (1).
The study reported that the results suggest the fiber blend could be used to “replace fiber depleted high fat snack foods” (1). The low-glycemic index snacks would then meet the needs of those with type 2 diabetes mellitus and those with cardiovascular disease (1).
The fiber blend was reported to be more effective in lowering glycemic response than other soluble fibers including psyllium hulls, glucomannan alone, beta-glucan, guar gum, pectin and ground flax seed (1).
Reference List
1. Jenkins AL, Jenkins DJ, Wolever TM et al. Comparable postprandial glucose reductions with viscous fiber blend enriched biscuits in healthy subjects and patients with diabetes mellitus: acute randomized controlled clinical trial. Croat Med J 2008;49:772-82. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=19090602. Accessed on 15 June 2009.
My Glycemic Load for the Day
My goal is to keep my glycemic load (GL) under 100 daily so let's see how I did today (all data from NutritionData.com):
Highest GL foods
2tbsp Honey (in my oatmeal) GL=20
1 Starbucks Caramel Mocha Frappuccino® Light Blended Creme GL=16
1 Plain Bagel GL=17
1 cup White Rice (with sushi) GL=18
1 packet Instant Oatmeal GL=10
Lowest GL foods
2 tbsp Sugar (with my green tea) GL=6
1 large Peach GL=5
1 Watermelon wedge GL=6
1 oz Blueberries GL=1
1 oz Raspberries GL=1
From the looks of it I scored exactly 100 today. Hooray! I could've done better. I didn't realize honey would add so much. Had I only used blueberries and raspberries in my oatmeal, then it would have dropped to 80. Yes, I realize I could've also gone without the Frapuccino, but it looked so good this morning.
One way that I often use to help lower the glycemic response of high-GL foods is by having them with a complete meal that includes protein, fiber and "good" fats. When it comes to those high-GL beverages I try to include a flavorless soluble fiber supplement such as psyllium hulls or digestion-resistant maltodextrin.
Highest GL foods
2tbsp Honey (in my oatmeal) GL=20
1 Starbucks Caramel Mocha Frappuccino® Light Blended Creme GL=16
1 Plain Bagel GL=17
1 cup White Rice (with sushi) GL=18
1 packet Instant Oatmeal GL=10
Lowest GL foods
2 tbsp Sugar (with my green tea) GL=6
1 large Peach GL=5
1 Watermelon wedge GL=6
1 oz Blueberries GL=1
1 oz Raspberries GL=1
From the looks of it I scored exactly 100 today. Hooray! I could've done better. I didn't realize honey would add so much. Had I only used blueberries and raspberries in my oatmeal, then it would have dropped to 80. Yes, I realize I could've also gone without the Frapuccino, but it looked so good this morning.
One way that I often use to help lower the glycemic response of high-GL foods is by having them with a complete meal that includes protein, fiber and "good" fats. When it comes to those high-GL beverages I try to include a flavorless soluble fiber supplement such as psyllium hulls or digestion-resistant maltodextrin.
Are glycemic index and glycemic load tools useful?
Strong evidence exists that low-glycemic and low-glycemic-load diets reduce risk of diabetes mellitus, obesity, insulin resistance, cardiovascular disease and cancer (1-4). However, glycemic index and glycemic load are subject of controversy among nutritionists because they are inconsistent in their findings due to high variability, are poorly standardized and their results are difficult to reproduce (1;2).
Despite methodological problems, however, studies are showing glycemic index and glycemic load are effective as clinical tools (3-5). According to one systemic review of 11 randomized controlled trials of four weeks or longer, low-glycemic diets helped patients control glycemic response in diabetes (3). One randomized, controlled trial also showed that a low-glycemic load diet may be more effective than a conventional low-fat, reduced-calorie diet in reducing risk of cardiovascular disease (5).
Athletes have also found glycemic index and glycemic load to be useful in improving performance. Moderate- to high-glycemic carbohydrates consumed after exercise have been found to enhance glycogen storage, and it’s thought that consumption of low-glycemic, carbohydrate-rich foods hours before an endurance event may provide lasting energy, although more research is needed to support this theory (6-8).
Reference List
1. Barclay AW, Petocz P, McMillan-Price J et al. Glycemic index, glycemic load, and chronic disease risk--a meta-analysis of observational studies. Am J Clin Nutr 2008;87:627-37.
2. Arteaga LA. The glycemic index. A current controversy. Nutr Hosp 2006;21 Suppl 2:53-60.
3. Thomas D, Elliott EJ. Low glycaemic index, or low glycaemic load, diets for diabetes mellitus. Cochrane Database Syst Rev 2009;CD006296.
4. Wolever TM, Jenkins DJ, Jenkins AL, Josse RG. The glycemic index: methodology and clinical implications. Am J Clin Nutr 1991;54:846-54.
5. Ebbeling CB, Leidig MM, Sinclair KB, Seger-Shippee LG, Feldman HA, Ludwig DS. Effects of an ad libitum low-glycemic load diet on cardiovascular disease risk factors in obese young adults. Am J Clin Nutr 2005;81:976-82.
6. Burke LM, Collier GR, Hargreaves M. Glycemic index--a new tool in sport nutrition? Int J Sport Nutr 1998;8:401-15.
7. Mitchell JB, Braun WA, Pizza FX, Forrest M. Pre-exercise carbohydrate and fluid ingestion: influence of glycemic response on 10-km treadmill running performance in the heat. J Sports Med Phys Fitness 2000;40:41-50.
8. Burke LM. Nutrition for post-exercise recovery. Aust J Sci Med Sport 1997;29:3-10.
Despite methodological problems, however, studies are showing glycemic index and glycemic load are effective as clinical tools (3-5). According to one systemic review of 11 randomized controlled trials of four weeks or longer, low-glycemic diets helped patients control glycemic response in diabetes (3). One randomized, controlled trial also showed that a low-glycemic load diet may be more effective than a conventional low-fat, reduced-calorie diet in reducing risk of cardiovascular disease (5).
Athletes have also found glycemic index and glycemic load to be useful in improving performance. Moderate- to high-glycemic carbohydrates consumed after exercise have been found to enhance glycogen storage, and it’s thought that consumption of low-glycemic, carbohydrate-rich foods hours before an endurance event may provide lasting energy, although more research is needed to support this theory (6-8).
Reference List
1. Barclay AW, Petocz P, McMillan-Price J et al. Glycemic index, glycemic load, and chronic disease risk--a meta-analysis of observational studies. Am J Clin Nutr 2008;87:627-37.
2. Arteaga LA. The glycemic index. A current controversy. Nutr Hosp 2006;21 Suppl 2:53-60.
3. Thomas D, Elliott EJ. Low glycaemic index, or low glycaemic load, diets for diabetes mellitus. Cochrane Database Syst Rev 2009;CD006296.
4. Wolever TM, Jenkins DJ, Jenkins AL, Josse RG. The glycemic index: methodology and clinical implications. Am J Clin Nutr 1991;54:846-54.
5. Ebbeling CB, Leidig MM, Sinclair KB, Seger-Shippee LG, Feldman HA, Ludwig DS. Effects of an ad libitum low-glycemic load diet on cardiovascular disease risk factors in obese young adults. Am J Clin Nutr 2005;81:976-82.
6. Burke LM, Collier GR, Hargreaves M. Glycemic index--a new tool in sport nutrition? Int J Sport Nutr 1998;8:401-15.
7. Mitchell JB, Braun WA, Pizza FX, Forrest M. Pre-exercise carbohydrate and fluid ingestion: influence of glycemic response on 10-km treadmill running performance in the heat. J Sports Med Phys Fitness 2000;40:41-50.
8. Burke LM. Nutrition for post-exercise recovery. Aust J Sci Med Sport 1997;29:3-10.
Sunday, June 14, 2009
Blood disorders
What is hemosiderosis?
Most iron is stored in the liver, lymph and skeletal muscles by use of a protein, ferritin (1). Ferritin consists of an apoprotein called apoferritin that is made up of H and L subunits (amino acids) synthesized dependent on concentration of free intracellular iron (1). Each protein can hold up from 3000 to 4500 iron atoms (1). When overload exceeds storage capacity, however, a partially degraded form of ferritin in spheres occurs called hemosiderin (1p252, 2p825). An accumulation of iron deposits via hemosiderin results in hemosiderosis (3).
What causes hemosiderosis?
Hemosiderosis can be inherited by way of a genetic mutation such as Bantu siderosis or Ferroportin disease. Previously thought to occur due to drinking too much beer, Bantu siderosis affects up to 10 percent of rural Africans and is associated with cirrhosis, heart disease and diabetes (4). Ferroportin disease is the most common genetic hemosiderosis and caused by gene mutation that disrupts ferroportin production (4).
Pulmonary hemosiderosis occurs due to over-accumulation of iron in the lung tissue (4). It can be a result of cardiovascular disease or a systemic disorder that mostly affects children (5). Anemia, lung scarring and coughing up blood are all symptoms (4). Corticosteroid therapy has been successful as a treatment and iron therapy or transfusion is important (5;6).
Renal hemosiderosis, hepatic hemosiderosis or other organ-specific hemosiderosis may occur due to hemolysis, leaving iron from hemoglobin to collect in the organs (4). Its cause can genetic or by an agent of some kind, which can lead to hepatocyte distruction and liver disease (5-8).
Transfusional hemosiderosis happens when a blood transfusion meant to treat anemia causes iron overload (4). Chelation therapy to extract iron is used to correct the problem (5;9).
What is Hb-C disorder?
Hemoglobin C disorder is a genetic missense mutation of hemoglobin resulting in a GAA or GAG codon for glutamate replaced with an AAA or AAG codon for lysine in the sixth position of a beta-globin (1p206). It is the most common hemoglobinopathy after sickle cell disorder (1p206).
What is pernicious anemia?
Pernicious anemia is not specifically an anemia, but a gastric disorder that can lead to megaloblastic anemia as well as neurological deterioration via demyelination of nervous tissue (1p1109, 2p483). The disorder was fatal until liver extracts were found in 1926 to be a cure (1p1109).
What is the cause of pernicious anemia?
The cause of pernicious anemia is lack of gastric intrinsic factor, which is required to absorb extrinsic factor cobalamin (vitamin B12), or a dietary deficiency of extrinsic factor cobalamin (1p1109, 2p483). Cobalamin is required for two enzymes in the body: methionine synthase, which drives homocysteine methylation to methionine, and methylmalmalonyl-CoA mutase, which drives conversion of methylmalonyl CoA to succinyl CoA (1p1109). Without cobalamin homocysteine and methylmalonic acid both accumulate causing the megaloblastic anemia (1p1109). The demyelination may be caused because methylmalonic acid inhibits and acts as a substitute for malonyl CoA in fatty acid biosynthesis (1p1110).
Reference List
1. Devlin TM. Textbook of Biochemistry with Clinical Correlations. Philadelphia: Wiley-Liss, 2002.
2. Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ. Modern Nutrition in Health and Disease. Baltimore, MD: Lippincott Williams & Wilkins, 2009.
3. Andrews GA, Chavey PS, Crawford G. Enzyme-linked immunosorbent assay to quantitate serum ferritin in black and white ruffed lemurs (Varecia variegata variegata). J Zoo Wildl Med 2005;36:648-52.
4. Aboutblooddisorders.com. Hemosiderosis and iron overload. Available at: http://www.about-blood-disorders.com/articles/iron-disorders/hemosiderosis.php. Accessed on 14 June 2009.
5. Deniz O, Onguru O, Ors F et al. Idiopathic pulmonary hemosiderosis in an adult patient responded well to corticosteroid therapy. Tuberk Toraks 2007;55:77-82.
6. YETTRA M, GOLDENBERG E, WEINER H. Idiopathic pulmonary hemosiderosis. Calif Med 1960;93:330-6.
7. Bale PM, Kan AE, Dorney SF. Renal proximal tubular dysgenesis associated with severe neonatal hemosiderotic liver disease. Pediatr Pathol 1994;14:479-89.
8. Carthew P, Dorman BM, Edwards RE, Francis JE, Smith AG. A unique rodent model for both the cardiotoxic and hepatotoxic effects of prolonged iron overload. Lab Invest 1993;69:217-22.
9. Giardina PJ, Grady RW. Chelation therapy in beta-thalassemia: the benefits and limitations of desferrioxamine. Semin Hematol 1995;32:304-12.
Most iron is stored in the liver, lymph and skeletal muscles by use of a protein, ferritin (1). Ferritin consists of an apoprotein called apoferritin that is made up of H and L subunits (amino acids) synthesized dependent on concentration of free intracellular iron (1). Each protein can hold up from 3000 to 4500 iron atoms (1). When overload exceeds storage capacity, however, a partially degraded form of ferritin in spheres occurs called hemosiderin (1p252, 2p825). An accumulation of iron deposits via hemosiderin results in hemosiderosis (3).
What causes hemosiderosis?
Hemosiderosis can be inherited by way of a genetic mutation such as Bantu siderosis or Ferroportin disease. Previously thought to occur due to drinking too much beer, Bantu siderosis affects up to 10 percent of rural Africans and is associated with cirrhosis, heart disease and diabetes (4). Ferroportin disease is the most common genetic hemosiderosis and caused by gene mutation that disrupts ferroportin production (4).
Pulmonary hemosiderosis occurs due to over-accumulation of iron in the lung tissue (4). It can be a result of cardiovascular disease or a systemic disorder that mostly affects children (5). Anemia, lung scarring and coughing up blood are all symptoms (4). Corticosteroid therapy has been successful as a treatment and iron therapy or transfusion is important (5;6).
Renal hemosiderosis, hepatic hemosiderosis or other organ-specific hemosiderosis may occur due to hemolysis, leaving iron from hemoglobin to collect in the organs (4). Its cause can genetic or by an agent of some kind, which can lead to hepatocyte distruction and liver disease (5-8).
Transfusional hemosiderosis happens when a blood transfusion meant to treat anemia causes iron overload (4). Chelation therapy to extract iron is used to correct the problem (5;9).
What is Hb-C disorder?
Hemoglobin C disorder is a genetic missense mutation of hemoglobin resulting in a GAA or GAG codon for glutamate replaced with an AAA or AAG codon for lysine in the sixth position of a beta-globin (1p206). It is the most common hemoglobinopathy after sickle cell disorder (1p206).
What is pernicious anemia?
Pernicious anemia is not specifically an anemia, but a gastric disorder that can lead to megaloblastic anemia as well as neurological deterioration via demyelination of nervous tissue (1p1109, 2p483). The disorder was fatal until liver extracts were found in 1926 to be a cure (1p1109).
What is the cause of pernicious anemia?
The cause of pernicious anemia is lack of gastric intrinsic factor, which is required to absorb extrinsic factor cobalamin (vitamin B12), or a dietary deficiency of extrinsic factor cobalamin (1p1109, 2p483). Cobalamin is required for two enzymes in the body: methionine synthase, which drives homocysteine methylation to methionine, and methylmalmalonyl-CoA mutase, which drives conversion of methylmalonyl CoA to succinyl CoA (1p1109). Without cobalamin homocysteine and methylmalonic acid both accumulate causing the megaloblastic anemia (1p1109). The demyelination may be caused because methylmalonic acid inhibits and acts as a substitute for malonyl CoA in fatty acid biosynthesis (1p1110).
Reference List
1. Devlin TM. Textbook of Biochemistry with Clinical Correlations. Philadelphia: Wiley-Liss, 2002.
2. Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ. Modern Nutrition in Health and Disease. Baltimore, MD: Lippincott Williams & Wilkins, 2009.
3. Andrews GA, Chavey PS, Crawford G. Enzyme-linked immunosorbent assay to quantitate serum ferritin in black and white ruffed lemurs (Varecia variegata variegata). J Zoo Wildl Med 2005;36:648-52.
4. Aboutblooddisorders.com. Hemosiderosis and iron overload. Available at: http://www.about-blood-disorders.com/articles/iron-disorders/hemosiderosis.php. Accessed on 14 June 2009.
5. Deniz O, Onguru O, Ors F et al. Idiopathic pulmonary hemosiderosis in an adult patient responded well to corticosteroid therapy. Tuberk Toraks 2007;55:77-82.
6. YETTRA M, GOLDENBERG E, WEINER H. Idiopathic pulmonary hemosiderosis. Calif Med 1960;93:330-6.
7. Bale PM, Kan AE, Dorney SF. Renal proximal tubular dysgenesis associated with severe neonatal hemosiderotic liver disease. Pediatr Pathol 1994;14:479-89.
8. Carthew P, Dorman BM, Edwards RE, Francis JE, Smith AG. A unique rodent model for both the cardiotoxic and hepatotoxic effects of prolonged iron overload. Lab Invest 1993;69:217-22.
9. Giardina PJ, Grady RW. Chelation therapy in beta-thalassemia: the benefits and limitations of desferrioxamine. Semin Hematol 1995;32:304-12.
Dyshemoglobinemia Dealings
Overview
Dyshemoglobinemias are mainly caused by exposure to exogenous xenobiotics although it can be hereditary (1). The occurrence is result of altered hemoglobin (Hb) preventing its normal function of carrying oxygen (1). The anemia, hypoxia, cyanosis and associated problems can be life-threatening (2).
Causes
Acquired methemoglobinimeas occur when dysfunctional hemoglobin form methemoglobin, whereas mutated amino acids make up a wall against heme or form the site involved in binding oxygen (3).
Carboxyhemoglobinemia is a form that results of exposure to carbon monoxide or nitrous oxide poisoning (4-6). It can occur as a result of overexposure to automobile exhaust, smoke from a fire or tobacco or nitrous oxide (4-6).
Sulfhemoglobinemia is a serious form that can occur when overexposed to sulfonamides or sulfur compounds such as when taking certain drugs (2;7;8).
Detection
Pulse oximetry is a non-invasive way to detect dyshemoglobinemia through monitoring the oxygenation of the blood (9;10). Invasive approaches of carbon monoxide oximetry or blood gas analysis also exist (10;11). Symptoms include cognitive changes, headache, fatigue, dizziness and syncope (12). If methemoglobinemia is greater, then dysrhythmias, seizures or coma can occur (12).
Treatment
An obvious measure is to eliminate exposure to the causal agent. Oxygen therapy can be used to increase oxygen carried by normal hemoglobin and, in extreme cases, blood transfusions may be necessary (12).
Reference List
1. Tintinalli JE, Kelen GD, Stapcynski JS. Emergency Medicine: A Comprehensive Study Guide. Columbus, OH: McGraw-Hill Professional, 2003.
2. Lambert M, Sonnet J, Mahieu P, Hassoun A. Delayed sulfhemoglobinemia after acute dapsone intoxication. J Toxicol Clin Toxicol 1982;19:45-50.
3. Devlin TM. Textbook of Biochemistry with Clinical Correlations. Philadelphia: Wiley-Liss, 2002.
4.Shperling IA, Novitskii VV, Riazantseva NV et al. [Mechanisms underlying changes in functional properties of red cells in acute action of carbon monoxide]. Patol Fiziol Eksp Ter 2008;18-20.
5. Rusca M, Oddo M, Schaller MD, Liaudet L. Carboxyhemoglobin formation as an unexpected side effect of inhaled nitric oxide therapy in severe acute respiratory distress syndrome. Crit Care Med 2004;32:2537-9.
6. Ren X, Dorrington KL, Robbins PA. Respiratory control in humans after 8 h of lowered arterial PO2, hemodilution, or carboxyhemoglobinemia. J Appl Physiol 2001;90:1189-95.
7. Flexman AM, Del VG, Schwarz SK. Dark green blood in the operating theatre. Lancet 2007;369:1972.
8. Martin DG, Watson CE, Gold MB, Woodard CL, Jr., Baskin SI. Topical anesthetic-induced methemoglobinemia and sulfhemoglobinemia in macaques: a comparison of benzocaine and lidocaine. J Appl Toxicol 1995;15:153-8.
9. Sinex JE. Pulse oximetry: principles and limitations. Am J Emerg Med 1999;17:59-67.
10. Michaelis G, Biscoping J, Salzer A, Hempelmann G. [Effect of dyshemoglobinemia (methemoglobinemia and carboxyhemoglobinemia) on accuracy of measurement in pulse oximetry in operations of long duration]. Anasth Intensivther Notfallmed 1988;23:102-8.
11. Akhtar J, Johnston BD, Krenzelok EP. Mind the gap. J Emerg Med 2007;33:131-2.
12. Masimo corporation. Demystifying Methemoglobinemia. Available at: http://www.masimo.com/pdf/whitepaper/LAB4280A.PDF
Dyshemoglobinemias are mainly caused by exposure to exogenous xenobiotics although it can be hereditary (1). The occurrence is result of altered hemoglobin (Hb) preventing its normal function of carrying oxygen (1). The anemia, hypoxia, cyanosis and associated problems can be life-threatening (2).
Causes
Acquired methemoglobinimeas occur when dysfunctional hemoglobin form methemoglobin, whereas mutated amino acids make up a wall against heme or form the site involved in binding oxygen (3).
Carboxyhemoglobinemia is a form that results of exposure to carbon monoxide or nitrous oxide poisoning (4-6). It can occur as a result of overexposure to automobile exhaust, smoke from a fire or tobacco or nitrous oxide (4-6).
Sulfhemoglobinemia is a serious form that can occur when overexposed to sulfonamides or sulfur compounds such as when taking certain drugs (2;7;8).
Detection
Pulse oximetry is a non-invasive way to detect dyshemoglobinemia through monitoring the oxygenation of the blood (9;10). Invasive approaches of carbon monoxide oximetry or blood gas analysis also exist (10;11). Symptoms include cognitive changes, headache, fatigue, dizziness and syncope (12). If methemoglobinemia is greater, then dysrhythmias, seizures or coma can occur (12).
Treatment
An obvious measure is to eliminate exposure to the causal agent. Oxygen therapy can be used to increase oxygen carried by normal hemoglobin and, in extreme cases, blood transfusions may be necessary (12).
Reference List
1. Tintinalli JE, Kelen GD, Stapcynski JS. Emergency Medicine: A Comprehensive Study Guide. Columbus, OH: McGraw-Hill Professional, 2003.
2. Lambert M, Sonnet J, Mahieu P, Hassoun A. Delayed sulfhemoglobinemia after acute dapsone intoxication. J Toxicol Clin Toxicol 1982;19:45-50.
3. Devlin TM. Textbook of Biochemistry with Clinical Correlations. Philadelphia: Wiley-Liss, 2002.
4.Shperling IA, Novitskii VV, Riazantseva NV et al. [Mechanisms underlying changes in functional properties of red cells in acute action of carbon monoxide]. Patol Fiziol Eksp Ter 2008;18-20.
5. Rusca M, Oddo M, Schaller MD, Liaudet L. Carboxyhemoglobin formation as an unexpected side effect of inhaled nitric oxide therapy in severe acute respiratory distress syndrome. Crit Care Med 2004;32:2537-9.
6. Ren X, Dorrington KL, Robbins PA. Respiratory control in humans after 8 h of lowered arterial PO2, hemodilution, or carboxyhemoglobinemia. J Appl Physiol 2001;90:1189-95.
7. Flexman AM, Del VG, Schwarz SK. Dark green blood in the operating theatre. Lancet 2007;369:1972.
8. Martin DG, Watson CE, Gold MB, Woodard CL, Jr., Baskin SI. Topical anesthetic-induced methemoglobinemia and sulfhemoglobinemia in macaques: a comparison of benzocaine and lidocaine. J Appl Toxicol 1995;15:153-8.
9. Sinex JE. Pulse oximetry: principles and limitations. Am J Emerg Med 1999;17:59-67.
10. Michaelis G, Biscoping J, Salzer A, Hempelmann G. [Effect of dyshemoglobinemia (methemoglobinemia and carboxyhemoglobinemia) on accuracy of measurement in pulse oximetry in operations of long duration]. Anasth Intensivther Notfallmed 1988;23:102-8.
11. Akhtar J, Johnston BD, Krenzelok EP. Mind the gap. J Emerg Med 2007;33:131-2.
12. Masimo corporation. Demystifying Methemoglobinemia. Available at: http://www.masimo.com/pdf/whitepaper/LAB4280A.PDF
Saturday, June 13, 2009
Isa News Sept Oct2007
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Isa News Sept Oct2007
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Friday, June 12, 2009
Iron Man
Iron is abundant in the world and needed by every living organism. For this reason early in evolution multi-cellular organisms evolved antimicrobial peptides(1). Without them we just wouldn't be able to survive the onslaught of microbial growth (1).
In addition, free iron in plasma has redox capabilities that can also be toxic. The toxicity is due to the Haber-Weiss-Fenton sequence, which forms hydroxyl radicals due to superoxide after reduction of dioxygen (1). The hydroxyl radicals can then act detrimentally on proteins, nucleic acids, carbohydrates and also cause lipid peroxidation (1).
In animals, heme is the moiety that holds a central iron atom within a porphyrin ring structure (1). Most of the body’s iron is contained as heme acting in various functions, but mainly necessary as an oxygen carrier within hemoglobin of blood cells and myoglobin in muscles (1). Heme synthesis requires iron to be in a reduced ferrous state, which is why ferriductases are important for iron metabolism (1).
Of the total amount of iron received from the diet, only 10 percent is generally absorbed. Of clinical importance, dietary iron is best if derived from animal products, which contains heme iron (1). Nonheme iron, found in both animal and plant-based foods, is not absorbed as well, although absorption of nonheme iron is increased at times of iron deficiency (1).
Reference List
1. McCord JM. Iron, free radicals, and oxidative injury. J Nutr 2004;134:3171S-2S. Available at: http://jn.nutrition.org/cgi/content/full/134/11/3171S.
2. Modern Nutrition in Health and Disease. Baltimore, MD: Lippincott Williams & Wilkins, 2009.
In addition, free iron in plasma has redox capabilities that can also be toxic. The toxicity is due to the Haber-Weiss-Fenton sequence, which forms hydroxyl radicals due to superoxide after reduction of dioxygen (1). The hydroxyl radicals can then act detrimentally on proteins, nucleic acids, carbohydrates and also cause lipid peroxidation (1).
In animals, heme is the moiety that holds a central iron atom within a porphyrin ring structure (1). Most of the body’s iron is contained as heme acting in various functions, but mainly necessary as an oxygen carrier within hemoglobin of blood cells and myoglobin in muscles (1). Heme synthesis requires iron to be in a reduced ferrous state, which is why ferriductases are important for iron metabolism (1).
Of the total amount of iron received from the diet, only 10 percent is generally absorbed. Of clinical importance, dietary iron is best if derived from animal products, which contains heme iron (1). Nonheme iron, found in both animal and plant-based foods, is not absorbed as well, although absorption of nonheme iron is increased at times of iron deficiency (1).
Reference List
1. McCord JM. Iron, free radicals, and oxidative injury. J Nutr 2004;134:3171S-2S. Available at: http://jn.nutrition.org/cgi/content/full/134/11/3171S.
2. Modern Nutrition in Health and Disease. Baltimore, MD: Lippincott Williams & Wilkins, 2009.
Sunday, June 7, 2009
Hominin diets could reveal a lot about our own
Just in case anyone's interested, I had the great opportunity to discuss nutrition science today with none other than Lucy discoverer Donald Johanson. What luck!
After explaining to Johanson of studying "evolutionary discordance" of diet post-agricultural revolution, he pointed me in the direction of a book related to hominin diets based on studies of hominin teeth.
This revelation led me to have a great interest in what further studies could be put together. I imagine randomized, controlled trials involving diets of humans on pre-human diets. Not only could the data help us better understand certain adaptions in our own digestive systems, but also what possible other "evolutionary discordances" that may have occured during a time when humans actually became human.
At the same event I spoke to another evolutionary biologist who suggested that fire had a key role in allowing our digestive system to adapt to a higher-energy diet.
The book recommended by Don Johanson was by Peter Ungar. A link to an article on the subject of diet and hominin teeth is found here.
After explaining to Johanson of studying "evolutionary discordance" of diet post-agricultural revolution, he pointed me in the direction of a book related to hominin diets based on studies of hominin teeth.
This revelation led me to have a great interest in what further studies could be put together. I imagine randomized, controlled trials involving diets of humans on pre-human diets. Not only could the data help us better understand certain adaptions in our own digestive systems, but also what possible other "evolutionary discordances" that may have occured during a time when humans actually became human.
At the same event I spoke to another evolutionary biologist who suggested that fire had a key role in allowing our digestive system to adapt to a higher-energy diet.
The book recommended by Don Johanson was by Peter Ungar. A link to an article on the subject of diet and hominin teeth is found here.
Saturday, June 6, 2009
Assessment: First-ever quality clinical on n-3 fatty acids for treatment of AD
Purpose of study: To evaluate potential treatment with use of n-3 fatty acids for those with mild to moderate Alzheimer’s disease (AD).
Research methodology: Randomized, double-blind, placebo-controlled clinical trial
Description: Researchers treated 204 patients with mild to moderate AD (ages 74 +- 9) with n-3 fatty acids or placebo for 6 months. All patients then received n-3 fatty acid treatment for the following 6 months. No cross-over trial was performed.
Patients were chosen for stability while on normal acetylcholine esterase inhibitor treatment and who had score of 15 points or more on a Mini-Mental State Examination (MMSE). During the study, the patients continued their regular treatment. Exclusions of the study included patients undergoing treatment with NSAIDs, other n-3 preparations or anticoagulants as also were those who had history of alcohol abuse or serious disease, or if did not have a caregiver.
The n-3 fatty acid treatment included 1.7g of docosahexaenoic acid (DHA) and 0.6 eicosapentaenoic acid (EPA) daily and the placebo group was treated with an isocaloric placebo of corn oil that included 0.6 g of linoleic acid daily.
Outcome Measurements: Cognitive measurement upon outcome included MMSE and cognitive portion of Alzheimer Disease Assessment Scale (ADAS).
Results: No statistical significant difference during 6 and 12 months for those with more advanced AD as revealed by MMSE and ADAS; however, a subgroup of mild dementia did show statistically significant treatment from MMSE scores over the duration of the study. The results found with the subgroup with mild dementia strongly suggest possibility of better cognitive performance and, perhaps, a role in “primary prevention of AD but not in treatment of manifest disease”.
Assessment: Despite lack of a cross-over trial included, this first-ever published randomized, double-bind, placebo-controlled study on treating AD with n-3 fatty acids presents valid data of excellent quality. The study, however, is limited in data on how differing amounts of n-3 fatty acids as well as differing ratios of EPA and DHA might have affected results. The researchers rightly suggest that more controlled intervention studies are needed to explore this area.
Reference: Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T et al. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Arch Neurol 2006;63:1402-8.
Research methodology: Randomized, double-blind, placebo-controlled clinical trial
Description: Researchers treated 204 patients with mild to moderate AD (ages 74 +- 9) with n-3 fatty acids or placebo for 6 months. All patients then received n-3 fatty acid treatment for the following 6 months. No cross-over trial was performed.
Patients were chosen for stability while on normal acetylcholine esterase inhibitor treatment and who had score of 15 points or more on a Mini-Mental State Examination (MMSE). During the study, the patients continued their regular treatment. Exclusions of the study included patients undergoing treatment with NSAIDs, other n-3 preparations or anticoagulants as also were those who had history of alcohol abuse or serious disease, or if did not have a caregiver.
The n-3 fatty acid treatment included 1.7g of docosahexaenoic acid (DHA) and 0.6 eicosapentaenoic acid (EPA) daily and the placebo group was treated with an isocaloric placebo of corn oil that included 0.6 g of linoleic acid daily.
Outcome Measurements: Cognitive measurement upon outcome included MMSE and cognitive portion of Alzheimer Disease Assessment Scale (ADAS).
Results: No statistical significant difference during 6 and 12 months for those with more advanced AD as revealed by MMSE and ADAS; however, a subgroup of mild dementia did show statistically significant treatment from MMSE scores over the duration of the study. The results found with the subgroup with mild dementia strongly suggest possibility of better cognitive performance and, perhaps, a role in “primary prevention of AD but not in treatment of manifest disease”.
Assessment: Despite lack of a cross-over trial included, this first-ever published randomized, double-bind, placebo-controlled study on treating AD with n-3 fatty acids presents valid data of excellent quality. The study, however, is limited in data on how differing amounts of n-3 fatty acids as well as differing ratios of EPA and DHA might have affected results. The researchers rightly suggest that more controlled intervention studies are needed to explore this area.
Reference: Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T et al. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Arch Neurol 2006;63:1402-8.
Assessment: Fish Consumption and Incidence of Stroke Meta-Analysis
Purpose of review: Further research was necessary into relationship between fish consumption and risk of stroke because observational studies were inadequate for determining relationship.
Review strategy: Meta-analysis on cohort studies relating to fish consumption and risk of stroke.
Description: Researchers searched Medline and Embase databases with relative keywords (e.g. “fish) to identify 9 total relevant cohorts (note: one study counted as two) published in English language journals from 1966 to 2003.
The cohort studies chosen each provided “relative risk” and “corresponding 95%” confidence interval factors for relationship of stroke with fish consumption. Duration average of each was 12.8 years with a range of 4 to 30 years. Each study had been properly adjusted for multiple covariates. Regional variance existed: of the 9 studies, 6 were from the U.S., 1 from Europe, 1 from China, and 1 from Japan creating a regional variance. Five of the studies attained data through personal interviews presenting variance with stratified analyses.
Disadvantages: The researchers note limitations in that most studies chosen “did not separate ischemic from hemorrhagic stroke”, which are different in etiology. It was noted that Japan and China studies presented a population of which may have higher risk of hemorrhagic stroke versus most studies from the U.S., where ischemic stroke is higher risk. Confounding variables from each cohort also must be taken into consideration.
Results: Review suggests “an inverse association between fish consumption and risk of stroke, particularly ischemic stroke, although there was not a strong dose-response relationship.”
Assessment: Large populations and different ethnic groups among the 9 cohorts introduce multiple variables that challenge this meta-analysis considerably. These would include, as noted in the study, even how and what kind of fish was cooked. The review also is limited in determining what amounts of fish should be eaten for most benefit or whether or not there was a relationship of stroke risk with amount of n-3 fatty acids.
Reference: He K, Song Y, Daviglus ML et al. Fish consumption and incidence of stroke: a meta-analysis of cohort studies. Stroke 2004;35:1538-42. Available at: http://stroke.ahajournals.org/cgi/reprint/35/7/1538?ijkey=50a74da6182d65ded6f8ab521844953e5469f6a6.
Review strategy: Meta-analysis on cohort studies relating to fish consumption and risk of stroke.
Description: Researchers searched Medline and Embase databases with relative keywords (e.g. “fish) to identify 9 total relevant cohorts (note: one study counted as two) published in English language journals from 1966 to 2003.
The cohort studies chosen each provided “relative risk” and “corresponding 95%” confidence interval factors for relationship of stroke with fish consumption. Duration average of each was 12.8 years with a range of 4 to 30 years. Each study had been properly adjusted for multiple covariates. Regional variance existed: of the 9 studies, 6 were from the U.S., 1 from Europe, 1 from China, and 1 from Japan creating a regional variance. Five of the studies attained data through personal interviews presenting variance with stratified analyses.
Disadvantages: The researchers note limitations in that most studies chosen “did not separate ischemic from hemorrhagic stroke”, which are different in etiology. It was noted that Japan and China studies presented a population of which may have higher risk of hemorrhagic stroke versus most studies from the U.S., where ischemic stroke is higher risk. Confounding variables from each cohort also must be taken into consideration.
Results: Review suggests “an inverse association between fish consumption and risk of stroke, particularly ischemic stroke, although there was not a strong dose-response relationship.”
Assessment: Large populations and different ethnic groups among the 9 cohorts introduce multiple variables that challenge this meta-analysis considerably. These would include, as noted in the study, even how and what kind of fish was cooked. The review also is limited in determining what amounts of fish should be eaten for most benefit or whether or not there was a relationship of stroke risk with amount of n-3 fatty acids.
Reference: He K, Song Y, Daviglus ML et al. Fish consumption and incidence of stroke: a meta-analysis of cohort studies. Stroke 2004;35:1538-42. Available at: http://stroke.ahajournals.org/cgi/reprint/35/7/1538?ijkey=50a74da6182d65ded6f8ab521844953e5469f6a6.
Assessment: n-3 fatty acids and cognitive decline study
Purpose of study: Observe how plasma n-3 fatty acids affect risk of cognitive decline in older adults.
Research methodology: Prospective human observational cohort study
Description: Beydoun et al (1) analyzed plasma fatty acids in cholesteryl esters and phospholipids in 2,251 white women and men ages 50-65 from 1987 to 1989 in a community in Minneapolis, MN. In subsequent years 1990 to 1992 and 1996 to 1998, researchers administered cognitive tests on the subjects.
Measurements: Blood analysis was performed through collection of 12-hour fasting blood followed by identity of peaks through gas chromatography. Reliability coefficient for the testing ranged from 0.50 to 0.93 for cholesteryl esters and from 0.50 to 0.89 for phospholipids.
Cognitive assessments included tests for delayed word recall, psychomotor speed and verbal fluency. The researchers properly noted that almost all subjects had education of high school or above, which was important to assure group comparability. Ages 65 and older were excluded to as not skew measurements as were those showing signs of early mental decline.
Problems: Disadvantages of this study were chiefly the amount of confounding variables, which required control through backward elimination. Despite the control and reducing subjects from initial 4,000 to the 2,251, the large amount of subjects introduced many covariates. As appropriate Beydoun et al reported a type 1 error level of 0.10 that was validated through statistical analysis.
Results: Study’s findings suggested n-3 fatty acids “may have substantial benefits in reducing risk of cognitive decline in the area of verbal fluency,” but did not suggest any benefit for psychomotor speed or delayed word recall. Further, findings revealed warranted enrichment of n-3 fatty acids in the diet of those with increased oxidative stress from hypertensive and dyslipidemia.
Assessment: Despite noteworthy effort on behalf of Beydoun et al to control variables by reducing the study to a homogenous population and by eliminating many covariates, the other multivariates acting as potential confounders leads me to agree with the researchers themselves that randomized, controlled, cross-over trials are necessary to determine more meaningful data.
Reference: Beydoun MA, Kaufman JS, Satia JA, Rosamond W, Folsom AR. Plasma n-3 fatty acids and the risk of cognitive decline in older adults: the Atherosclerosis Risk in Communities Study. Am J Clin Nutr 2007;85:1103-11. Available at: http://www.ajcn.org/cgi/content/full/85/4/1103.
Research methodology: Prospective human observational cohort study
Description: Beydoun et al (1) analyzed plasma fatty acids in cholesteryl esters and phospholipids in 2,251 white women and men ages 50-65 from 1987 to 1989 in a community in Minneapolis, MN. In subsequent years 1990 to 1992 and 1996 to 1998, researchers administered cognitive tests on the subjects.
Measurements: Blood analysis was performed through collection of 12-hour fasting blood followed by identity of peaks through gas chromatography. Reliability coefficient for the testing ranged from 0.50 to 0.93 for cholesteryl esters and from 0.50 to 0.89 for phospholipids.
Cognitive assessments included tests for delayed word recall, psychomotor speed and verbal fluency. The researchers properly noted that almost all subjects had education of high school or above, which was important to assure group comparability. Ages 65 and older were excluded to as not skew measurements as were those showing signs of early mental decline.
Problems: Disadvantages of this study were chiefly the amount of confounding variables, which required control through backward elimination. Despite the control and reducing subjects from initial 4,000 to the 2,251, the large amount of subjects introduced many covariates. As appropriate Beydoun et al reported a type 1 error level of 0.10 that was validated through statistical analysis.
Results: Study’s findings suggested n-3 fatty acids “may have substantial benefits in reducing risk of cognitive decline in the area of verbal fluency,” but did not suggest any benefit for psychomotor speed or delayed word recall. Further, findings revealed warranted enrichment of n-3 fatty acids in the diet of those with increased oxidative stress from hypertensive and dyslipidemia.
Assessment: Despite noteworthy effort on behalf of Beydoun et al to control variables by reducing the study to a homogenous population and by eliminating many covariates, the other multivariates acting as potential confounders leads me to agree with the researchers themselves that randomized, controlled, cross-over trials are necessary to determine more meaningful data.
Reference: Beydoun MA, Kaufman JS, Satia JA, Rosamond W, Folsom AR. Plasma n-3 fatty acids and the risk of cognitive decline in older adults: the Atherosclerosis Risk in Communities Study. Am J Clin Nutr 2007;85:1103-11. Available at: http://www.ajcn.org/cgi/content/full/85/4/1103.
Understanding Pernicious Anemia
Intrinsic factor, a glycoprotein secreted from paretal cells in the stomach, is responsible for forming a complex with cobalamin (B12) to then bind to an ileal receptor for absorption (1p1184). Lack of ability to secrete intrinsic factor results in pernicious anemia, a megaloblastic anemia from cobalamin deficiency(1;2). Pernicious anemia therapy often requires parenteral cobalamin or oral cobalamin in high enough doses (1).
Identifying megaloblastic anemia in a Complete Blood Count:
RBC - Decreases
Hb - Decreases
MCV - Increases
MCH - Stays the Same
MCHC - Stays the Same
(3)
Reference List
1. Modern Nutrition in Health and Disease. Baltimore, MD: Lippincott Williams & Wilkins, 2009.
2. Saladino, C. "Week 1 Lecture, Part 1." Clinical Biochemistry [Lecture Series], 2009.
3. Medicine.net. "Complete Blood Count". Available at http://www.medicinenet.com/complete_blood_count/article.htm. Accessed on June 06, 2009.
Identifying megaloblastic anemia in a Complete Blood Count:
RBC - Decreases
Hb - Decreases
MCV - Increases
MCH - Stays the Same
MCHC - Stays the Same
(3)
Reference List
1. Modern Nutrition in Health and Disease. Baltimore, MD: Lippincott Williams & Wilkins, 2009.
2. Saladino, C. "Week 1 Lecture, Part 1." Clinical Biochemistry [Lecture Series], 2009.
3. Medicine.net. "Complete Blood Count". Available at http://www.medicinenet.com/complete_blood_count/article.htm. Accessed on June 06, 2009.
Friday, June 5, 2009
Life adapted to the beach or the cooking pot?
Last night I met up with perhaps the most famous biologist on the planet, PZ Myers. How? He was just hanging out at a bar in town. Couldn't believe my luck! I brought up all my evolutionary nutrition ideas to him.
In case anyone's interested (does anyone read this blog?), PZ was fond of this recent article of Wrangham who wrote Catching Fire: How Cooking Made Us Human.
The book, by the way, pretty much shuts down the raw-foodist movement suggesting that cooking was absolutely essential for our species to get along in the world.
Also, I brought up archaeologist Curtis Marean's suggestion that "humans adapted to a life on the beach" eating shellfish and gaining omega-3 oils to form bigger brains.
PZ raised his eyebrows and said something like, "Humans are just too opportunistic to have been that limited in diet."
He went on to discuss amylase gene copy number variations of which I found fascinating. Nature article about it here.
In case anyone's interested (does anyone read this blog?), PZ was fond of this recent article of Wrangham who wrote Catching Fire: How Cooking Made Us Human.
The book, by the way, pretty much shuts down the raw-foodist movement suggesting that cooking was absolutely essential for our species to get along in the world.
Also, I brought up archaeologist Curtis Marean's suggestion that "humans adapted to a life on the beach" eating shellfish and gaining omega-3 oils to form bigger brains.
PZ raised his eyebrows and said something like, "Humans are just too opportunistic to have been that limited in diet."
He went on to discuss amylase gene copy number variations of which I found fascinating. Nature article about it here.
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