Biomarkers of Wellness

1. Biomarkers of Wellness

2. “What Gets Measured- Gets Managed” Peter Drucker

3. What language do you speak?

4. Body Mass Index (BMI) • BMI = Weight(in kg) Height2(in meters) • Lbs/ inches2 x 703 • A BMI of <25 = desirable 25 – 29.9 = overweight >30 = obese

6. Bray GA. Overweight is risking fate. Definition, classification, prevalence and risks. Ann NY Acad Sci 1987;499:14-28. Relationship of BMI to Excess Mortality 20-40yoa 300 Age at Issue 20-29 250 30-39 200 150 Mortality Ratio 100 High Moderate Low Risk Risk Risk 50 0 15 20 25 30 35 40 Body Mass Index (kg/[m2])

7. BMI & Obesity The 773 morbidly obese female members had used a mean of $11,145 in medical insurance expenses in the year 2003 versus a mean of $8,096 for the other 106,908 adult women (27% higher). Similar values for the men were $16,720 for the 138 morbidly obese men versus $5,943 for the other 82,490 men. (64% higher)

8. BMI ≠ Body Fat While BMI certainly tells us how unhealthy a person is, it doesn’t tell us how healthy a person is. Example, a skinny fat person aka sarcopenic obesity

9. #1 Biomarker of Aging “. . . no decline with age is as dramatic or potentially more significant than the decline in lean body mass.” J Nutr 127:990S-991S (1997)

10. Body Fat Over a lifetime 30% of muscle mass is lost From age 20, women lost 5 – 7 lbs of muscle @ decade 25% weight loss on a typical diet is muscle One lb of muscle burns at least 3Xs the calories as one lb of fat

11. Biochemistry of Vitamin D

12. What is a vitamin? • Organic compound • Required to support life • Generally a co-factor for enzyme activation (most B vitamins) or antioxidant (E and C) • Must be obtained from the diet • Cannot be synthesized in adequate quantities

13. Vitamin D, on the other hand… • Can be synthesized in the body • Has receptors and target tissues …More accurately characterized as a pro-hormone • Since it is synthesized by the body from cholesterol, it is not necessarily “essential” that it be supplied by diet.

14. Historical understanding of vitamin D • Fundamental to calcium and phosphorus metabolism • Deficiencies/insufficiencies related to: • Rickets • Osteomalacia • Osteoporosis • 400 IU/day is currently the RDI • The amount shown to prevent rickets

15. Vitamin D is called the “sunshine” vitamin • It is manufactured in the skin from cholesterol upon exposure to UV radiation. • Healthy (RDI) levels of vitamin D production can be achieved by: • 10-15 minutes of sun exposure • Hands, forearms and face • 3-5 times per week • Spring, summer fall months only

16. Dietary vitamin D is found in two forms: • Vegetable • Ergocalciferol/D2 • Manufactured from the plant sterol ergosterol • Synthetic form of the vitamin • Animal • Cholecalciferol/D3 • Manufactured from cholesterol • Both can be converted to active hormone 1,25-(OH)2 D3,(also called calcitriol) via a two-step hydroxylation first in the liver, then in the kidneys. • May also be hydroxylated in the colon, breast, lungs and prostate.

17. Look a bit closer and vitamin D gets more interesting… • Vitamin D regulates uptake of calcium from the gut through stimulation ofgene expression • Activating the production of calcium-binding proteins such as calbindin that increase calcium absorption. • Upwards of 200 genes are believed to be regulated by Vitamin D, most of which are not involved in mineral metabolism. • Essentially every tissue and cell in the body has a vitamin D receptor.

18. Blood levels of vitamin D below 20 ng/mL led to 30-50% increased risk of developing and dying from various cancers (colorectal, breast, prostate etc.) • Low 25(OH)D levels are associated with all-cause mortality and even more pronounced with cardiovascular mortality • Women with blood vitamin D level <12 ng/mL had a 253% increased risk of colerectal cancer • Highest levels of vitamin D consumption correlated with a 50% lower risk of breast cancer. • Teenagers with frequent sun exposure had a 35-40% reduced risk of breast cancer as adults.

19. There’s more… • Low sun exposure for the first 10 years of life doubles the risk to multiple sclerosis development. • Children receiving ~2000 IU of vitamin D daily had 78% reduced risk to development of type I diabetes. • Vitamin D lowered BP to normal levels • Low blood vitamin D level is associated with depression, autoimmune disease, osteoarthritis, increased susceptibility to infection, even postulated as a cause of seasonal cold and flu.

20. Today, a number of factors have contributed to what one researcher calls a “deficiency pandemic” of vitamin D • Aggressive campaign to use sunscreen has led to a significant segment of the population with vitamin D deficiency • Use of sunscreen results in a 99% reduction of vitamin D production • Fewer people get out in the sun regularly • Fear of skin cancer • Work location/habits (garage to car to office to car to garage) • Changing perceptions of beauty • Aging and skin tone reduce the efficiency of vitamin D synthesis • People of color require 5-10 times longer sun exposure compared to Caucasians to make the same amount of vitamin D

21. Vitamin D levels in our society • An estimated 1 billion people worldwide are thus considered deficient • Adults >65 • 52% of postmenopausal women • 36% of young adults 18-29 had vit D levels <20 ng/mL at the end of winter, in spite of consuming fortified milk or multivitamin daily. • In a group of 40 mother-infant pairs tested at birth, 76% of the mothers and 81% of the infants had vit D <20 ng/mL

22. Current requirements: • <20 ng/mL: deficient • 21-29 ng/mL: insufficient • >30 ng/mL: adequate • If insufficient or deficient, it may take >10,000 IU/day to attain adequate levels.

23. To sum up… “Vitamin D has evolved into a hormone that is active throughout the body, not only to regulate calcium and bone metabolism, but to control cellular growth, regulate immune function, and control production of insulin and renin among other hormones. All healthcare professionals should be alert to the vitamin D deficiency pandemic.” Michael Holick, University of Boston

24. Waist/Hip Ratio • Waist/Hip Ratio Ideal: .70<.80 Woman and <.95 Man • 50 years ago the average women’s was 27” and today it’s 34” • A size 8 in 1950 is a size 4 today • Adipose Tissue is the largest endocrine gland in the body and produce: • Inflammatory chemicals • Estrogen • Cortisol

25. What Does the Adipocyte Secrete?Heber D: PCRI Insights, May 2004 Vol 7, No.4

26. Blood Pressure • Blood Pressure Systolic less than or equal to 110mm-Good Diastolic equal to or less than 70mm-Good Greater than 130/85mm is Mildly Hypertensive

27. Any why you should care • ALLHAT compared 4 BP drug classes • study proved diuretics is just as good as the other 3 more expensive class of drugs • Top 50 drugs for seniors in 2001, Norvasc is #2. • Diuretics were # …… >50 • 37/hr for diuretics; $715/yr Norvasc (2002)

28. 2006 Top 10 Drugs $9,000,000,000

29. In case you were wondering • 9 billion dollars will buy • 3,409,090 8 Weeks to Wellness Programs in our office • 2,141,051 8 Weeks to Wellness Programs in Dr. Prakash’s office

30. Sugar Biomarkers • Diabetes is the seventh leading cause of death listed on U.S. death certificates. • Cardiovascular disease is the leading cause of death among people with diabetes — about 68 percent die of heart disease or stroke. • Total health care and related costs for the treatment of diabetes run about $174 billion annually. • Actos world wide drug sales are $2.5 Billion, the 9th best selling drug in America. • In 1967, 3000 tons of HCFS were produced and 2007 over 9,000,000 tons of HCFS were produced

31. How much sugar is in your body 100mg x 10 dl X 5 liters X 1 grams = 5 grams = 1 teaspoon dl liter 1000 mg Normal Fasting Glucose: 80-100 mg/dl

32. A BMJ investigation into the top-selling diabetes drug rosiglitazone (Avandia) raises concerns about its safety and the whole system by which drugs are evaluated, regulated, and promoted around the world. Sept. 7, 2010

33. HbA1C • Equal to % of RBCs that are glycated • You can run but you can’t hide from HbA1C because once a RBC is glycated, it stays that way. • “The predictive value of HbA1C for total mortality was stronger than that documented for cholesterol concentration, body mass index and blood pressure.” BMJ 2001

35. Insulin • Fasting Insulin Increased insulin production causes insulin resistance • Hyperinsulinemia is associatd with inflammastion in the brain and triggers increase in plaques that are hallmark of Alzheimer’s (JAMA 2006) • The neurodengeration that occurs in AD is linked with abnormal insulin signaling (J Alzheimers Disease 2005) • Insulin resistance also linked to depression, bipolar disease, autism, and schizophrenia.

36. Lipid Biomarkers • Total Cholesterol = HDL + LDL + VLDL • HDL = 33% protein, 30% cholesterol, carries cholesterol from the body to the liver • LDL = 25% protein, 50% cholesterol, carries cholesterol to the body from the liver

37. Tidbits • Cholesterol Endogenous > Exogenous • South African egg farmers consume 1,240 mg per day, their average cholesterol is 181.4 (RDA is 300 mg) • NEJM reported on a 88 year old man who ate 25 eggs per day for 30 years, weighed 185 at 6’2” and had a normal cholesterol level. • On the island of Crete, the incidence of CVD is lowest in the world and the average serum cholesterol is over 200. • Cholesterol is a necessary molecule in the body and accounts for over half the weight of the brain’s cortex. • At least 5% - 7% of statin users experience significant muscle problems.

38. More Tidbits • Cardiomyopathy (serious weakening of the heart muscle) is a known adverse and often not reported side effect of statin therapy. • Cholesterol is the precursor to all hormones and, therefore, is vital to the many functions of the endocrine system including sexual function. • Cholesterol is found in the cell wall of each one of the 70 trillion cells in your body. • When cholesterol gets too low, you could suffer from memory loss, sexual dysfunction, low blood pressure leading to dizziness, and loss of libido. • Reducing the manufacture of cholesterol in the liver simultaneously reduces the production of Co-Enzyme Q10 - a vital anti-oxidant essential for healthy heart function. (Rather counter productive, don’t you think?) • Cholesterol is a precursor to serotonin -- a key hormone to feeling good and sleeping well. • And last but certainly not least…these cholesterol-lowering drugs DO NOT reduce the deaths due to heart disease. If you don’t believe this, just look for this disclaimer on the ads and website of the leading cholesterol-lowering drugs.

39. Lipid Biomarkers • Lipids, fractionated lipids • Total Cholesterol-under 200 • Triglycerides-under 150, preferably under 100 • HDL-over 50 (male) and over 60 (female) • LDL-under 130 • Trig/HDL ratio- under 2.0 • Chol/HDL ratio- under 3.0 • High Tri/HDL – predicts heart attack 17X often (AHA 1995)

40. C – reactive protein • CRP is a protein found in the blood, the levels of which rise in response to inflammation. • CRP rises up to 50,000-fold in acute inflammation, such as infection. It rises above normal limits within 6 hours, and peaks at 48 hours. Its level is mainly determined by the rate of production (and hence the severity of the precipitating cause). • Levels above 2.4 mg/l has been associated with a doubled risk of a coronary event compared to levels below 1 mg/l. • CRP & Statins: "the number of patients who would need to be treated with Crestor for 2 years to prevent the occurrence of one primary end point is 95, and the number needed to treat for 4 years is 31." In other words, after four years of treatment, out of every 31 patients, one cardiovascular event would be prevented. • Physical fitness is inversely related to CRP level in children and that this relationship is more pronounced in boys than in girls. (Pediatrics 2003) • Insulin resistance and C-reactive protein (CRP) levels are strongly correlated in adults

41. $35,000,000,000 = 11,670,556 8ww programs in Dr. Tremblay's office

42. Liberty + Responsibility = Freedom