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Application of Nutrition knowledge in Clinical practice

Application of Nutrition knowledge in Clinical practice. 中研院生醫所 潘文涵 Wen-Harn Pan Institute of Biomedical Sciences Academia Sinica. Application of nutrition knowledge. Primary care Secondary care Tertiary care Future prospective Nutrigenomics Individualized medicine

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Application of Nutrition knowledge in Clinical practice

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  1. Application of Nutrition knowledge in Clinical practice 中研院生醫所 潘文涵 Wen-Harn Pan Institute of Biomedical Sciences Academia Sinica

  2. Application of nutrition knowledge • Primary care • Secondary care • Tertiary care • Future prospective • Nutrigenomics • Individualized medicine • Screening for high risk group

  3. Primary care • Balanced diet • Six food groups 1. Cereal (3-7) 2. Protein rich foods (4) 3. Limited amount of fat 4. Fruits (2) 5. Vegetables (3) 6. Dairy products (1-2)

  4. Adequate distribution and kinds of fat, protein, and carbohydrate-rich foods • Low fat / whole grain diet • Reduced calorie  obesity • Reduced colon cancer risk • Beriberi • Proper fatty acid composition  • Lower blood cholesterol • Anti-inflammation • Anti-coagulation • Red meat (rich in heme-iron, SAFA, and vit B1) • Prevent iron-deficiency anemia/beriberi • Increase serum cholesterol

  5. Enough fruits and vegetables • Rich in antioxidants and phytochemicals • Prevent scurvy, night blindness • Lower risk of CAD and cancer • Rich in folate • Prevent hyper-homocysteinemia • SAMe production • Rich in fiber • Improve bowel movement • Lower risk of colon cancer • Rich in minerals (Ca, Mg, K) • Lower risk of • Osteoporosis • Diabetes • Cerebral hemorrhage

  6. Seconary care • Taiwanese Examples • Folate and stroke and cataract • Folate, B6, anemia, and depression

  7. The relationship between folate status and chronic disease in Taiwanese elderly people 1. Folic acid is an important cofactors in the transfer and utilization of one carbon moieties and play a key role in the synthesis of nucleic acids and homocysteine metabolism. 2. Several studies indicated that folate deficiency may associated with risk of vascular disease.

  8. (vitB2)

  9. Atherosclerosis Atherosclerosis ? Nephrosclerosis Primary arterial thrombosis Myocardial infarction Stroke Elevated Homocysteine Low folate Low vitamin B2 Low vitamin B12 Low vitamin B6 MTHFR mutant Other Venous thrombosis Venous thromboembolism Hyperhomocysteine與Atherosclerosis

  10. Dietary Intake of Folate and Risk of Stroke in US Men and Women-NHANESΙFollow-Up Study (Stroke,33:1183-1189,2002)

  11. Adjusted Odds ratio of Transient ischemic attack in Taiwanese elderly population 1 Model A: put the related risk factor of stroke enter the model. 2 Model B: put the related risk factor of stroke and nutritional factor enter the model. 3 Model C: put the related risk factor of stroke, homocysteine and C-reactive protein enter the model. 4 Model D: Full model.

  12. Adjusted Odds ratio of marginal folate deficiency for stroke and cataract by 林璧鳳、陳冠如(台大生化與微生物研究所） Self-reported Physician-diagnosed stroke and cataract Odds ratio adjusted for age, sex, waist-hip ratio, systolic blood pressure, diastolic blood pressure, blood sugar, plasma creatinine, serum cholesterol, HDL-cholesterol, plasma vitaminB2, B6 and B12.

  13. Adjusted Odds ratio of marginal folate deficiency for stroke and cataract in normal nutritional status of vitaminB2, vitaminB6 and vitamin B12 subjects1 1.Criteria of the vitamin status: normal folate status : plasma folate > 6ng/ml. Marginal folate deficiency : 3~6ng/ml normal vit B2 status: plasma EgRAC < 1.2 normal vit B6 status : plasma PLP > 20 nmole/L. normal vit B12 status: plasma B12 >258 pmol/L. 2.Stroke and cataract: adjusted for age, sex, waist-hip ratio, systolic blood pressure, diastolic blood pressure, blood sugar, plasma creatinine, serum cholesterol and HDL-cholesterol.

  14. In the Taiwanese elderly population who have sufficient vitaminB2, B6 and B12 status, low folate status may contribute to the increased risk in stroke, renal disease and cataract.

  15. 文獻回顧：(葉酸與動脈硬化、中風之關係)

  16. However, few studies have prospectively examined the relationship between dietary intake of folate and the risk of cardiovascular diseases.

  17. 葉酸與白內障

  18. 維生素營養狀況與白內障之相關性 1.白內障：眼睛水晶體呈現渾濁的一種症狀。 白內障是影響老年人視力功能最常見的疾病，亦是導致失明的主要原因。 2.白內障的重要危險因子有年齡、抽煙、喝酒、低身體質量指數 (Body mass index;BMI)(Ritter et al, 1993; Leske et al, 1991; West et al, 1989)。 3.有研究顯示抗氧化維生素在延緩白內障的發生上，扮演重要角色(Jacques & Chylack, 1991)。 4.類胡蘿蔔素、VitA、菸鹼酸、vitB1與 vitB2，具有降低白內障的 危險性(Mares-Perlman et al, 1994；Hankinson et al, 1992; Bunce et al, 1990)。

  19. 5.調整年齡、抽煙、喝酒等危險因子後，補充VitA、VitC、VitE、vitB1和菸鹼酸，可以降低男性罹患白內障的危險性；補充葉酸可以降低女性罹患白內障的危險性(Mares-Perlman et al, 1995)。 6.調整年齡、抽煙、高血壓、身體質量指數、夏日陽光暴露時間及酒精攝取量後，增加VitC、vitB2、葉酸的攝取量，可以降低白內障的危險性(Jacques et al, 2001)。 7.長時期補充VitA、葉酸、vitB12等維生素，可以增加白內障的保護效果；但補充vitB2，則不具有保護白內障的效果。作者推測葉酸、vitB12等維生素攝取量降低，除了與同半胱胺酸濃度上升有關外，尚會影響DNA的合成，可能與白內障的形成有關(Kuzniarz et al, 2001)。

  20. 台灣老年人白內障危險性之多因子探討 1 Model A: 放入白內障的危險因子(例如：性別,年齡,身體質量指數，血糖和肌酸酐)。 2 Model B: 放入白內障的危險因子與營養因子(例如：葉酸、紅血球麩胱甘肽還原酶活性係數、磷酸砒哆醇和vitaminB12)。 3 Model C: 放入白內障的危險因子及同半胱胺酸。 4 Model D: 放入白內障的危險因子、營養因子、同半胱胺酸。

  21. 任一維生素B缺乏狀況下之白內障的調整危險對比值任一維生素B缺乏狀況下之白內障的調整危險對比值 1調整性別，年齡，身體質量指數，血糖，肌酸酐及同半胱胺酸等危險因子。 2 folate(＋), VitB2 (＋), VitB6 (＋), VitB12 (＋) 表示維生素B營養狀況正常Folate (－), VitB2 (－),VitB6 (－), VitB12 (－)代表維生素B瀕臨缺乏。

  22. 營養狀況與老人沮喪之關係 • 研究目的: 使用「 1999-2000國民營養健康狀況變遷老人 調查」的資料，探討營養素不足及相關症狀 「貧血」是否和老年沮喪有關係 • 分析: 將SF-36的沮喪相關問題的資訊和血液中維生素B6、 B12及葉酸和血紅素、攜鐵蛋白的濃度以對數回歸 分析法相互關連 • 結果: 當單一的血紅素過低，血紅素、維生素B6、葉酸三 者中均偏低或其中兩項數值偏低時老人沮喪的危險 性均較高（OR＝2─6倍） • 此現象似乎無法由疾病狀態、或用藥情況來解釋

  23. Table 1. 角色情緒與血紅素、維生素B6與葉酸 正常/缺乏組合之邏輯斯迴歸分析

  24. Table 2. 心理健康與血紅素、維生素B6與葉酸 正常/缺乏組合之邏輯斯迴歸分析

  25. DASH • "DASH" stands for "Dietary Approaches to Stop Hypertension," a clinical study that tested the effects of nutrients in food on blood pressure. Study results indicated that elevated blood pressures were reduced by an eating plan that emphasizes fruits, vegetables, and low-fat dairy foods and with reduced saturated and total fat. (N Engl J Med 1997;336:1117-24.)

  26. Influence of weight reduction on blood pressure: a meta-analysis of randomized controlled trials.Hypertension. 2003 Nov;42(5):878-84. • A meta-analysis of randomized controlled trials was performed to estimate the effect of weight reduction on blood pressure overall and in population subgroups. Twenty-five randomized, controlled trials (comprising 34 strata) published between 1966 and 2002 with a total of 4874 participants were included. • This meta-analysis of 25 RCTs comprising 4874 participants from different ethnic populations showed a BP reduction of -4.4/-3.6 mm Hg for an 5-kg weight loss by means of energy restriction, physical activity, or both.It clearly shows that weight loss is important for the prevention and treatment of hypertension.

  27. Potassium and CVD risk • Using Time Dependent Hazard Model to Compare the Cardiovascular Mortality of Elderly Males in a Potassium-Containing Salt Trial Hsing-Yi Chang1, Wen-Harn Pan1 • This research examines the cardiovascular mortality of a group of elderly males in a low sodium (potassium substitute) salt trial. The trial was a pseudo randomization trial. The randomization was done in the kitchens of a veteran’s retired home in the north of Taiwan. The trial started in October 17, 1995 and lasted till June 30, 1999. Altogether 2197 subjects participated the trial, 769 were in the low sodium diet group and 1428 were in the regular salt diet group. Their average age when entering the veterans’ home was around 74 years. There were 581 deaths in the study period, 93 of them died of cardiovascular diseases.

  28. What’s needed to be done?To promote application of nutrition knowledge in clinical practice

  29. Establish protocol for clinical identification of malnutrition • Set up lifestyle assessment modules • Simple dietary, anthropometric, and PA assessment • Nutritional biochemistry lab • Life style and dietary supplement intervention • Pre-testing  supplement/dietary counseling  post-testing • Novel way to collaborate with nutritionists/dietetics

  30. Core facilities for Nutritional Biochemical LABBiochemical indicators of nutrient intake

  31. Primary care • Balanced diet • Six food groups 1. Cereal (3-7) 2. Protein rich foods (4) 3. Limited amount of fat 4. Fruits (2) 5. Vegetables (3) 6. Dairy products (1-2)

  32. Trends and technologies in nutrition science Personalized diets THE AMERICAN DIETETIC ASSOCIATION (2003) , S50-55

  33. Food-Gene interaction

  34. Nutrigenomics:Goals • The identification of transcription factors that function as nutrient • sensors and the genes they target. • (2) The elucidation of the signaling pathways involved, and • characterization of the main dietary signals. • (3) The measurement and validation of cell- and organ-specific • gene expression signatures of the metabolic consequences of • specific micronutrients and macronutrients. • (4) The elucidation of the interactions between nutrient-related • regulatory pathways and proinflammatory stress pathways, • to understand the process of metabolic dysregulation that leads • to diet-related diseases.

  35. Nutrigenomics:Goals (5) The identification of genotypes that are risk-factors for the development of diet related human diseases (such as diabetes,hypertension or atherosclerosis) and quantification of their impact . (6) The use of nutritional systems biology to develop biomarkers of early metabolic dysregulation and susceptibility (stress signatures) that are influenced by diet.

  36. 48 members in the human genome is the important group of nutrient sensors Nature reviews/genetics (2003) , 4:315-322

  37. Lipids or specific FAs Atherosclerosis Insulin resistance cirrhosis Detecting the two hits: pro-inflammatory andmetabolic stress • The interaction between pro-inflammatory stress and metabolic stress • is the key to understanding diet-related diseases. • 2. Be able to identify early molecular biomarkers. Nature reviews/genetics (2003) , 4:315-322

  38. Ⅲ、Nutrigenomics:Strategies

  39. Two Strategies • The traditional hypothesis-driven approach: specific genes and proteins, the expression of which is influenced by nutrients, are identified using genomics tools — such as transcriptomics, proteomics and metabolomics — which subsequently allows the regulatory pathways through which diet influences homeostasis to be identified . Transgenic mouse models and cellular models are essential tools . • provide us with detailed molecular data on the interaction • between nutrition and the genome . • (2)The SYSTEMS BIOLOGY approach: gene, protein and metabolite signatures that are associated with specific nutrients, or nutritional regimes, are catalogued, and might provide ‘early warning’molecular • biomarkers for nutrient-induced changes to homeostasis. • Be more important for human nutrition, given the difficulty of • collecting tissue samples from ‘healthy’ individuals.

  40. Use model organisms in nutrition research Caenorhaboditis elegans (completed genome segence) Role of nutrients in Alzhelmer and Parkinson diseases. Zebrafish (Danio rerino) Role of nutrients in development and organ functions. Role of nutrition in development and organ functions. Mouse

  41. Use model organisms in nutrition research Knockout mice is useful ！ HNF, hepatocyte nuclear factor; LXR, liver X receptor; MTF1, metal-responsive transcription factor; PPAR,peroxisome proliferator-activated receptor; TGF, transforming growth factor. Nature reviews/genetics (2003) , 4:315-322

  42. Nutrigenomics and nutritional systems biology apply the same set of technologies Nutrition (2004) , 20: 4-8

  43. The ‘smart’ combination of molecular nutrition and nutrigenomics. Nature reviews/genetics (2003) , 4:315-322

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