Key Nutritional Considerations & Lab Markers as Adjuncts in Effective Lipid Management. Carmen Ritz, MS Clinical Physiologist

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1 Key Nutritional Considerations & Lab Markers as Adjuncts in Effective Lipid Management Carmen Ritz, MS Clinical Physiologist

2 The Ideal Biomarker to identify risk for CVD Specific accurately identifies those at risk Sensitive correctly identifies those not at risk Total Cholesterol doesn t quite meet either criteria, even from the beginning with the Framingham study. As better assays were developed HDL & LDL became the focus

3 HDL & Triglycerides are both Specific & Sensitive in Assessing & Managing Risk for CVD Cardiometabolic Disorders And then consider measuring the Insulin

lipoprotein cholesterol (HDL-C) and total cholesterol.

4 Twelve-year risk of myocardial infarc4on shown for Framingham cohort according to quar4les of high-density lipoprotein cholesterol (HDL-C) and total cholesterol. Women Men Lipids and Vascular Disease: A Framingham Perspective

5 HDL even more Specific than LDL Beyond LDL Cholesterol: The Role of Elevated Triglycerides and Low HDL Cholesterol in Residual CVD Risk Remaining After Statin Therapy, March 27, 2009; Review. for every 1-mg/dL (0.026 mmol/l) increase in plasma HDL cholesterol in the populations studied, there was a decrease in CHD risk of approximately 2% in men and 3% in women independent of other risk factors, including plasma LDL cholesterol. more than one third of the overall US adult population has low HDL cholesterol. Thirty-five percent of adult men and 39% of adult women were reported to have HDL cholesterol below 40 mg/dl and 50 mg/dl, respectively. Low HDL cholesterol is a significant, independent risk factor for CHD. Often, low HDL cholesterol is correlated with elevations of serum TG and remnant lipoproteins, and is strongly and inversely associated with CHD risk.

6 Does Lowering Chol or LDL lower risk or mortality? Effect of Statin Treatment vs Usual Care on Primary Cardiovascular Prevention Among Older Adults: The ALLHAT-LLT Randomized Clinical Trial. JAMA Intern Med Jul 1;177(7): doi: /jamainternmed CONCLUSIONS AND RELEVANCE: No benefit was found when pravastatin was given for primary prevention to older adults with moderate hyperlipidemia and hypertension, and a nonsignificant direction toward increased all-cause mortality with pravastatin was observed among adults 75 years and older.

7 Combining LDL-C and HDL-C to predict survival in late life: The InChianti study. PLoS One Sep 28;12(9):e doi: /journal.pone ecollection individuals over 64 years were included. CVD and cancer mortality were defined by ICD-9 codes and , respectively. LDL-C <130 mg/ dl (3.36 mmol/l) was defined as "optimal/near optimal". Low HDL-C was defined as <40/50 mg/dl (1.03/1.29 mmol/l) in males/females, respectively. Nine-years mortality risk was calculated by multivariate Cox proportional hazards model. We found that, compared to subjects with high LDL-C and normal HDL-C (reference group), total mortality was significantly increased in subjects with optimal/near optimal LDL-C and low HDL-C. CONCLUSIONS: Our findings suggest that, in community dwelling older individuals, the combined presence of optimal/near optimal LDL-C and low HDL-C represents a marker of increased future mortality.

8 Lipid levels in patients hospitalized with coronary artery disease: An analysis of 136,905 hospitalizations in Get With The Guidelines

9 What Biomarkers are consistent in identifying risk and when improved consistently associated w lower mortality or improved outcomes? Triglyceride / HDL / Insulin Association of high-density lipoprotein cholesterol with incident cardiovascular events in women, by low-density lipoprotein cholesterol and apolipoprotein B100 levels: a cohort study. Ann Intern Med Dec 6;155(11): doi: / CONCLUSION: Consistent inverse associations were found for HDL-C with incident coronary events among women with a range of LDL-C values. Among women with low total atherogenic particle burden (apolipoprotein B100 level <0.90 g/l), few events occurred and no associations were seen. High TG/Low HDL, indicative of risk for CARDIOMETABOLIC DISEASE : a constellation of metabolic dysfunction characterized by insulin resistance and impaired glucose tolerance, atherogenic dyslipidemia, hypertension and intra-abdominal adiposity (IAA).

10 Cardiovascular Disease Cardiometabolic Disorder Metabolic Syndrome Insulin Resistance The metabolic syndrome was identified as a practical way to identify persons at high risk to develop vascular disease in the National Cholesterol Education Program's adult treatment guidelines that were published in Lipids and Vascular Disease: A Framingham Perspective Controversies in dyslipidaemia management While coronary mortality rates have declined over the last few decades, this is challenged by the epidemic of cardiometabolic disease, the major challenge for healthcare providers in the 21st century. This epidemic is not restricted to industrialised countries. China in particular has been in the spotlight. Despite improved access to better treatment, an increasingly Westernised diet has escalated rates of dyslipidaemia and cardiovascular disease. It is estimated that cardiovascular disease rates in China will increase by more than 50% over the next 20 years.

11 FASTING INSULIN Cardiometabolic Disorder / Metabolic Syndrome Insulin Resistance Identifying prediabetes using fasting insulin levels. Endocr Pract Jan-Feb;16(1): doi: /EP09031.OR. CONCLUSIONS: women with a fasting insulin level around 8.0 had twice the risk of prediabetes as did women with a level around 5.0. Women with a fasting insulin of 25 or so had five times the risk of prediabetes. Elevated fasting insulin predicts the future incidence of metabolic syndrome: a 5-year follow-up study Cardiovascular Diabetology201110:108 Results/Conclusions: In a model that included gender, age, the smoking status, the exercise level, alcohol consumption and the systolic blood pressure, the subjects in the highest quartile of the insulin levels had more than a 5 times greater risk of developing MS compared that of the subjects in the lowest quartile. This predictive importance remained significant even after correcting for all the individual features of MS. These data suggest that high baseline fasting insulin levels are independent determinants for the future development of MS.

12 What s a Healthy Fasting Insulin Level? NHANES III Elevated fasting insulin is a hallmark of the metabolic syndrome, the modern metabolic disorder that affects 24% of Americans. The average insulin level in the U.S., is 8.8 uiu/ml for men and 8.4 for women. Given the incidence of metabolic syndrome in Americans, the ideal level of fasting insulin is probably below 8.4 uiu/ml. Functional Medicine Recommendations: Optimal range: 1-9 µu/ml Intermediate risk range: µu/ml High risk range: 12 µu/ml Medscape: Fasting <25mlU/L

13 So What Works to Lower Insulin Resistance & Insulin Levels What can : ü stimulate body fat loss ü reduce insulin & insulin resistance ü reduce Triglycerides ü AND increase HDL Following Key Nutritional Concepts

14 ? Low Carb? Mediterranean? Paleo? Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study High carbohydrate intake was associated with higher risk of total mortality, whereas total fat and individual types of fat were related to lower total mortality. Total fat and types of fat were not associated with cardiovascular disease, myocardial infarction, or cardiovascular disease mortality, whereas saturated fat had an inverse association with stroke. Global dietary guidelines should be reconsidered in light of these findings. The Lancet Volume 390, No , p , 4 November 2017http:// article/piis (17) /fulltext Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet Results: Low-carb and Mediterranean diets showed greater improvements over low-fat for weight-loss, lipid changes at two years. Mediterranean and low-carbohydrate diets may be effective alternatives to low-fat diets. The more favorable effects on lipids (with the low-carbohydrate diet) and on glycemic control (with the Mediterranean diet) suggest that personal preferences and metabolic considerations might inform individualized tailoring of dietary interventions N Engl j med 359;3 july 17, 2008 Beneficial effects on fatty acid composition and indices of fatty acid desaturase activity with a Paleolithic-type diet during a two-year intervention in obese postmenopausal women Postmenopausal women assigned to a high-protein Paleolithic-type diet saw greater reductions in fatty acids associated with insulin resistance than women assigned to a low-fat diet. The diet, which was 30% protein, 30% carbohydrates, and 40% fats, reduced intake of saturated fatty acids by 19% and increased intake of polyunsaturated fatty acids by 47%. ENDO 2016; April 1-4, 2016; Boston, MA.

15 The Basic Metabolic Principles A Complex Carb A Carb Sugar / GLUCOSE ** This requires INSULIN ** ANY excess Glucose in the presence of INSULIN Fat Anabolism The Body regulates Blood Glucose levels in a strict range. High levels of Glucose are toxic: requiring INSULIN, accelerating oxidation, inflammation. Low Carb = Glucose = Insulin = KETOSIS using Fat for energy source ** FAT Catabolism Ketosis Gluconeogenesis the liver produces the glucose, regulated by the body s requirements. No highs or lows. Gluconeogenesis = Stable Blood Glucose levels between ** This allows minimal INSULIN, Fat Anabolism ** NO Hypoglycemia = NO Blood Glucose swings = No excessive hunger ** Increased Satiety w eating = easier to eat less / to get Hypocaloric

Low Carb Infers higher Protein & Fat, low sugar, higher soluble fiber & vegetables Higher healthy mono unsaturated & saturated fats Limits most high carb sources: grains, cereals, potatoes, rice To

16 Low Carb Infers higher Protein & Fat, low sugar, higher soluble fiber & vegetables Higher healthy mono unsaturated & saturated fats Limits most high carb sources: grains, cereals, potatoes, rice To induce Ketosis: 30% or less of total calories. Mediterranean Infers high monounsaturated fats Seafood Higher soluble fiber & vegetables Paleo Infers NO GRAINS, Higher protein & fat, higher soluble fiber & vegetables Omits certain Neolithic foods : Dairy, potatoes, corn syrup, high Omega 6 vegetable oils

17 These Key Nutritional Concepts ü stimulate body fat loss ü reduce insulin & insulin resistance; from 5-25 µu/ml** ü reduce Triglycerides; from mg/dL** ü AND increase HDL from 5-25 mg/dl** ** anecdotal per personal case studies

18 LOW CARB RESOURCES: Background & How To 1. Good Calories Bad Calories ; Gary Taubes 2. The Art & Science of Low Carb Living ; Stephen Phinney, MD PhD; Jeff S. Volek, PhD 3. The Obesity Code: Unlocking the Secrets of Weight Loss ; Jason Fung, MD 4. DietDoctor.com PALEO 1. Balance Bites.com ; great 21 Day Sugar Detox program 2. Practical Paleo, 2 nd edition; Diane Sanfilippo 3. The Paleo Diet: Lose Weight and Get Healthy by Eating the Foods You Were Designed to Eat ; Loren Cordain, PhD MEDITERRANEAN 1. Mediterranean Paleo Cooking ; Caitlin Weeks, Chef Nail Boumrar, Diane Sanfilippo 2. The Ketogenic Mediterranean Diet: A Low-Carb Approach to the Freshand-Delicious, Heart-Smart Lifestyle ; Robert Santos-Prowse

13/09/2012. Dietary fatty acids. Triglyceride. Phospholipids:

13/09/2012. Dietary fatty acids. Triglyceride. Phospholipids: CARDIOVASCULAR DISEASES (CVD) and NUTRITION Major cause of morbidity & mortality in Canada & other developed countries e.g., majority of approved health claims on food labels relate to lowering CVD Relation