Alternative Medicine/Diet/Supplements Update from A-Z ... · Urol Clin N Am 2004;31:289-300....

Alternative Medicine/Diet/Supplements Update from A-Z: What Works & What is Worthless

Dr. Moyad Disclosures• Consultant/Speaker Abbott Labs

• Consultant Embria Health Sciences

• Consultant Farr Labs

• Consultant Guthy-Renker

• Royalty from 1 formulated product Guthy-Renker

• Author of Books-Spry Publishing

Evidence-Based Medicine & ADT Lifestyle/Suppl/Rx…: Forest over

the Tree & Less is More?! Mark A. Moyad, MD, MPH

Jenkins/Pokempner Director of Preventive/Alternative Medicine

University of Michigan Medical CenterAnn Arbor, MI

[email protected]:Talking about Michigan

¸


MEN

1. Cardiovascular Disease 426,772

2. Cancer 286,741

3. Accidents 67,923

4. Respiratory Diseases 60,456

5. Diabetes 35,217

www.cdc.gov, 2010.

Probability Based Medicine• #1 for only 110 out of 111 years?

• #1 in cancer prevention trials?

• #1 after localized pca cancer treatment?

• #1 or #2 cause of death on ADT? (Always High-Risk)

BOTTOM LINE=HEART Healthy=ALL HEALTHY!!!

Moyad MA. & Roach. Urol Clin N Am 2011; August.Moyad MA, Carroll PR. Urol Clin N Am 2004;31:289-300.

“Phase 3” Trials=Nothing(does it matter anyway?)

Bolla (2002)-EORTC 22863-EBRT vs. EBRT + 3 years ADT

No significant risk in CVD mortality

Roach (2008)-RTOG 8610 EBRT +/- 4 months ADT

No significant risk in fatal cardiac events

Efstahiou (2008)-RTOG 9202 EBRT 4 vs 28 months ADT

Longer ADT=No increase in cardiac mortality

Efstahiou (2009)-RTOG 8531 EBRT +/-lifelong ADT

No significant increase in CVD mortality

Bolla (2009)-EORTC 22961 EBRT 6 months vs 3yr ADT


Jones (2009)-RTOG 9408 EBRT +/- 4 months ADT


Moyad MA, Roach M, et al. Submitted…Other Meds/Supple with ADT?Other Phase 3? Alzheimer’s?


“Over-Anti-Oxidation Of Our Population!”

Moyad MA, Carroll PR. Urol Clin N Am 2004;31:289-300. & Moyad MA. AUA Update 37 & 38, 2008.

SELECT

-35,000 men

-300 sites

-150 milliondollars

1 Death From Prostate Cancer…& _____ deaths from heart disease.

-400 IUVitamin E Increased risk of Prostate Cancer (bleeding)

-200 mcgSelenium increasedRisk of type II diabetes


SELECT TRIAL-More is Not Better!

• In 1996 the average Selenium Level=114 ng/ml (Clark LC, et al. Br J Urol 1998;81:730-734.)

• In 2003 the average selenium level =135 ng/ml

Lippman SM, et al. SELECT. JAMA 2009;301:39-51

F=Folic Acid-Polyp Prevention Study Group (1mg/d)

SIDE EFFECT

FOLIC ACID(n=516)

PLACEBO(n=505)

RESULT

Colon Cancer 3 (0.5%) 4 (1%) No impact

Other Cancers

54 (10.5%)(24=p ca)

32 (6.3%)(9=p ca)

P=0.02!!!

Cole BF, et al: JAMA 297:2351-2359, 2007. Folate Receptor? UMFA?


MULTIVITAMINS• NIH-AARP study & Other Supplementation(N=10,000 cases, -1500 Advanced)

• Double the risk of advanced/fatal p. cancer

Bottom Line =??????????? Kids…Lawson KA, et al. J Natl Cancer Inst 99:754-764, 2007.

A =Anemia and ADT

A = Anemia? (Check the MCV)

• Median reduction Hb=1.2 g/dL

• 10% reduction in 90% men

Bottom Line = Normochromic Normocytic – expect it acutely, but usually never needs ANY intervention

Fonseca R et al. Am J Hematol. 1998;59:230–233. Strum SB et al. Br J Urol. 1997;79:933-941.


E=Exercise/Wt Lifting• Australia Study (10 men, age=70)• 20 wk high-intensity resistance exercise (5 months)• 5 men on acute & 5 on chronic ADT

• Increased Muscle Strength, No change in Fat Mass• No bone loss at any site + No Hgb change!

Bottom Line=Exaggerated?

Galvao DA, et al. (Spry N, Newton R…). Pros Cancer Prostat Dis, 2006.

B = Belly Fat/Weight Gain and ADT


3,500 calories=

1 POUND

100-200 cal/day=

10-20 lb pounds

Subcutaneous(Liposuction)

Vs.

Visceral Fat(Gastric Bypass)

Vs.

Animal Data

B=Belly Fat

B=BELLY FAT(Saturated Fat=Higher Calories!)

TYPE OF MILK SATURATED FAT (8 oz)

TOTAL CALORIES

Skim Milk 0 grams 80 Calories

1% Milk 1.5 grams 100 Calories

2% Milk 3 grams 120 Calories

Whole Milk 5 grams 150 Calories

Strom SS, et al. Int J Cancer 2008;122:2581-2585.


B = Belly FatBaltimore Longitudinal Study

• n=444• Q1=No risk (1063 cal)• Q2=OR=1.22 (1394 cal)• Q3=2.91 (1667 cal)• Q4=2.12 (2033 cal)• Q5=3.79 (2624 cal)

Fewer Calories = Lower PSA Velocity* (PCPT)Reduce Calories Everywhere…Hsieh LJ et al. Urology. 2003;61:297-301Kristal AR et al. Cancer. 2006;106:320–328.

Metformin + Lifestyle/Diet (new drug to fight side effects?)

• Generic Drug

• BREAST CANCER (Phase 3 trial)

• (3 FDA Weight loss drugs rejected)

• Bottom Line=Why not combine with hormone therapy?

Jalving M, et al. Metformin: Taking away the candy for cancer? Eur J Cancer 2010;46:2369-2380.


JUST IN!...Metformin + Low-Glycemic/Cal Diet + Exercise

PARAMETER (N=40, 6 months) METFORMIN VS CONTROL RESULT(% Change from mean)

Waist Circumference (cm) -0.58 vs. +2.15 (p=0.05)

BMI -3.19 vs. +2.10 (p<0.001)

Weight (kg) -3.19 vs. +2.18 (p<0.001)

Body fat (%) -5.48 vs. +6.47 (p=0.08)

Systolic BP -5.96% vs. +1.77 (p=0.01)

NO CHANGE IN LIPIDS NO CHANGE IN LIPIDS(Hgb A1C reduced, p=0.07)

Repeat of Diabetes Prevention Program Study! Survival?

Nobes JP, et al. A prospective, randomized pilot study evaluating the effects of metformin and lifestyle intervention on patients with pca receiving ADT….BJU Int…on-line early

B = Bone Loss

C=Calcium (Heart Attacks?!!!!)1000-1200 mg/d (Food?)

CALCIUMCARBONATE

CALCIUMCITRATE

CALCIUMPHOSPHATE

Panju AH, et al BJU Int 2009;103:753-7. & Bolland MJ, et al. BMJ 2010;341:C3691.


Study Profile:n = 176 menAge = 71Calcium = 1200 mg/dVit D = 700 IU/D3

Dawson-Hughes B et al. N Engl J Med. 1997;337(10):670-676.

No bone loss at:- Spine- Total Body- Femoral Neck

Prospective Clinical Trials-Bone Loss-1 YEAR (% loss)??????????

• Berruti (N=42)-No mets• Daniell (N=26)-No mets• Diamond (N=12)-Mets• Eriksson (N=11)-No mets• Higano (N=37)-No mets• Maillefert (N=12)-No mx• Mittan (N=15)-No mets• Smith (N=22)-No mets• Smith (N=51)-No mets

• Total hip:-0.6 Lspine:-2.3• Femoral neck:-2.4 to -3.4• Fem neck:-6.5 LS:-6.6• Fem neck:-9.6 Rad:-4.5• Fem neck:-1.1 LS:-4.0• Fem neck:-3.9 LS:-4.6• Total hip:-3.3 Rad:-5.3• Total hip:-1.8 LS:-3.3• LS:-1.9 to -2.7

Oefelein MG, Resnick MI. Urol Clin N Am, May, 2004.

Mean of 3-7%/PER YEAR >>Menopause

Smith MR et for Denosumab HALT Pca Study Group

• N=1482, Randomized vs. Placebo, 75 yrs, BMI=28

• Calcium=1000 mg, Vit D=400 IU+• No Resistance Activity• Primary Endpoint=% Change in BMD at Lspine• 24 Months=-1.0% Bone Loss at Spine (placebo)

Sanders KM, et al. JAMA 2010; 303:1815-1822.


D=Vitamin D Deficiency???

-Aging

-Belly Fat (lose weight=more vitamin D)

-High Cholesterol

-Poor Diet (Fish) or Fortification

-Lack of exercise

Moyad MA. AUA Update 2010.

Vitamin D is Safe in Mega-Doses???

• 500,000 IU per year (10 x 50,000)=FAILED!!!

• 3/14 Positive Studies (Low 25-OH & Low 1,25)

• 3/14 Negative Studies (Largest U.S.)

Sanders KM, et al. JAMA 2010; 303:1815-1822…..Barnett CM, Beer TM. Urol Clin N Am 2011;38:333-342

Vitamin D Blood Test?Vitamin D Blood Tests Normal Levels25 (OH)-hydroxy-vit D

1,25-dihydroxy-vit D

30 ng/mL - 40 ng/mL(75 nmol/L -100 nmol/L)

15-75 pg/ml

Bischoff-Ferrari HA et al. Am J Clin Nutr. 2006;84:18–28.

Need 1000 IU per day to MAXIMUM.


New Rx Drug that will hit the market on November, 1, 2011?

• Breast/Colon/Prostate Cancer

• Reduces BONE LOSS• Reduces

Dementia/Alz/Memory Loss

• Reduces Depression• Reduces E.D.• Reduces F.S.D.• Reduces Heart Disease• Reduces Incontinence

• Reduces Kidney Stones• Reduces Premature Death• Reduces Prostate

Enlargement• Reduces Prostate

Inflammation• Improves Sleep• Reduces Stress• Reduces Stroke• Reduces Type 2 Diabetes

Exercise!!!Now Are You Going Take It Daily!!• Breast/Colon/Prostate

Cancer• Reduces BONE LOSS• Reduces

Dementia/Alz/Memory Loss

• Reduces Depression• Reduces E.D.• Reduces F.S.D.• Reduces Heart Disease• Reduces Incontinence

• Reduces Kidney Stones• Reduces Premature Death• Reduces Prostate

Enlargement• Reduces Prostate

Inflammation• Improves Sleep• Reduces Stress• Reduces Stroke• Reduces Type 2 Diabetes


F = Fatigue(& Sarcopenia)

Weight-Lifting& Cancer

Lymphedema Study BreastCancer(2x/wk)

-Type 2 Diabetes

Segal RJ, et al. J Clin Oncol 2009;27:344-351. & Schmitz KH, et al. N Engl J Med 2009;361:664-673.

Segal RJ, et al. J Clin Oncol. 2003; 21:1653-1659.

Study Fitness Regimen(Caffeine & American Ginseng)

• Calf raise• Leg extension• Leg curl• Chest press• Latissimus pull-down

• Overhead press• Triceps extension• Biceps curl• Modified curl-up

2 sets8-12 repetitions

3 times per week


Aerobic vs. Weight LiftingHEALTH AREA AEROBIC WT. LIFTINGBone Health Yes!!!Burn Fat/Metab Yes!!! Yes!!!Strength Yes!!!Glucose/Insulin Yes!!! Yes!!!Lipids + hs-CRP Yes!!! (HDL!!!)HR/BP at rest Yes!!!Mental Health Yes!!! Yes!!!Overall Survival ? ?Braith RW, Stewart KJ. Circulation 113:2642-2650, 2006.

Exercise then Protein=Anti-Aging?

• SARCOPENIA???

• 20 grams of protein powder

• Muscle protein synthesis…

Pennings B, et al. Am J Clin Nutr, published ahead of print, 2011.

PROTEIN POWDERS???PROTEIN POWDER More COMMENT

Whey Protein Concentrate Cheap, Allergenic

Whey Protein Isolate More costly

Whey Protein Hydrolysate/Micronized More costly

Egg White Protein Just as good as Whey protein

Soy Protein Powder Best Source of Plant Protein

PROTEIN BARS? Watch those calories!

Moyad MA. Urol Clin N Am 2011, published Sept…on-line


H = Hot Flashes or Hot Flushes

(Use A Hot Flash Diary Before You Give An Rx)

Hot Flashes• Progesterone (20 mg) >Venlafaxine (75 mg)• Only 22% Requested Treatment

• Women’s Studies• Fish Oil, Sage, Flaxseed?? Diary…

Irani J, et al. Lancet 2009, December 7. & Moyad MA. Prom Wellness for Pca, 2011.

L = Lipid/Glucose ChangesCVD Risk???


Aspirin-Meta-Analysis

CONDITION RISK REDUCTIONColorectal 59% ReductionProstate 48% Reduction

Rothwell PM, et al. Lancet 2011;377:31-41.

10% Risk or greater of Heart Disease please!

Low-Dose ASA per 1000 treated for 5 years (meta=5 trials=>55,000)

CHD event risk/yr

CHD Events Avoided

Ischemic StrokesAvoided

Hem Strokes from ASA

Major Bleeds from ASA

Low=<10%

5 0 1 5

Moderate=10-20%

14 0 1 5

High=>10%

25-50 25-50 1 5

www.reynoldsriskscore.org or Framingham Risk Score

HMG-CoA

HMG-CoAreductase

StatinsOr Diet…

Mevalonate

Mevalonate-PP

Isopentenyl-PP

Geranyl-PP

Farnesyl-PP

Cholesterol

Steroids, Vitamin D, Bile acids, Lipoproteins

Farnesylated proteins:RASDolicholHeme-A

Geranylgeranyl-PP

Squalene Geranylgeranylated Proteins:UbiquinoneRhoRacRab

Moyad MA. Sem Prev Alt, submitted.


O’Keefe JH, et al. J Am Coll Cardiol 2004;43:2142-2146.

JUPITER Trial!LDL hs-CRP WHAT

HAPPENED?>70 >1 mg/L -9% Reduction

>70 <1 mg/L -35% Reduction

<70 >1 mg/L -50% Reduction

<70 <1 mg/L -79% Reduction!!!

Ridker PM, et al. Lancet 373:1175-1182, April 4, 2009. Justification for the Use of Statins in Prevention..

-DVT?

STATINS=Pca Mortality?Jacobs (2007) N=55,454

(317 adv)Followed=6-years

-40% Adv/Fatal P Ca.

Flick (2007) 69,047 (131) 14 years -43%

Murtola (2007)

49,446 (3680)

8 years -25% (CC)

Platz (2006) 34,989 (316) 13 years -50%

Marcella (2009)

380 cases 10 years -63%DEATHS!!!

(Murtola TJ, et al. Nature Clin Pract Urol 2008;5:376—387.)


Statins as an adjuvant?• Sloan-Kettering, retrospective, n=905 (T1-T3)• Median follow-up=39 months• 5-yr freedom-PSA recurrence (88.8% vs 71.2%)

Bottom Line=w/androgen suppression-statinsreduced risk of PSA recurrence.Katz MO, et al. Proceedings from ASCO: page S271-abstract# 1016, 2003.

N=938, 9-year follow-up…(Moyad MA ,Merrick G et al. Urol August/Sept 2006)

PARAMETER STATINS NON-STATINS

Overall Survival 94% 81%

Pooled Analysis of Phase 3 Trials & Statins (6 month on ADT, n=1102)

LIPIDPARAMETER

STATINS(Mostly atorvastatin-30%!)

NON-STATINS

HDL CHOLESTEROL Significant Increase Significant Increase

LDL CHOLESTEROL Non-significant reduction Significant Increase

TRIGLYCERIDES INCREASE INCREASE

Yannucci J, et al. J Urol 2006; 176:520-525.

Note: Anti-androgen reduces HDL & Triglycerides


F = Fish Oil + Statins(N=18000,Triglycerides Reduced)

Measurements (4.6 yrs) Results

Major Coronary Events Reduced 19% (P=0.011)

Fatal Heart Attack Reduced 21%

Non-Fatal Heart Attack Reduced 25%

Unstable Chest Pain Reduced 24%

Need of a Procedure Reduced 14%

Yokoyama M et al. Lancet. 2007;369:1090–1098.

-Reduced Risk of Insulin Resistance?

F=Fish oil pills & Quality Control(CR-2011)

1) Kirkland Signature (Costco) (0.06 day/$22-yr)

9) GNC

2) Member’s Mark (Sam’s Club)

10) Nature’s Bounty-Salmon Oil

3) Spring Valley 11) Rite Aid4) Walgreens 12) YourLife5) Vitasmart (Kmart) 13) Country Life6) CVS Pharmacy 14) Eckerd7) Natrol 15) Spectrum Essentials8) Sundown 16) Solgar-Omega-3 “700”

Statins are expensive??? Atorvastatin=Lipitor® ? (2011-ouch!)

Lovastatin=Mevacor® Generic

Pravastatin=Pravachol® Generic

Rosuvastatin=Crestor® ?

Simvastatin=Zocor® Generic

Moyad MA. Urol Clin N Am 2011, August.

RED YEAST RICE EXTRACT?


FOREST OVER THE TREE-52 COUNTRIES STUDY!!!

• 90-95% REDUCTION!

• 70% Chance of living to the age of 85 withoutmental or physical disability. (100?)

• 3% Americans

INTERHEART STUDY INVESTIGATORS. Lancet 364:937-952, Sept 11, 2004/2006/2008 Update.

FOREST OVER THE TREE-52 COUNTRIES STUDY!!!

1) Do you SMOKE?=10-15%2) Low CHOLESTEROL (LDL<100)?=10%3) Normal BLOOD PRESSURE (not pre-hyperten)=10%4) Normal GLUCOSE=10%5) Normal WC/WHR/No Belly Fat=10-15%6) Normal MENTAL HEALTH/STRESS=10%7) FRUITS & VEGGIES>1 serving/day=5%8) MODERATE ALCOHOL=10%9) EXERCISE AVERAGE OF 30 MIN/DAY=10%


HEART HEALTH=Improves Androgen Deprivation Health!

1. Mediterr Plant-Based Diet (low cal)

2. Low Glycemic3. Aerobic every OTHER

day4. Wt Lifting 2x/week5. Caffeine &/or Am

Ginseng6. Calcium WITH vit D7. Fish Oil (1000 mg)

8. ASA-if qualify?9. Statin &/or Metformin?10. High-dose of:-Multi=No!-Folic Acid=No!-Selenium=No!-Vitamin D=No!-Vitamin E=No!-Zinc=No!

Moyad MA & Roach M. Urol Clin, Aug, 2011.

What You Are Supposed To Worry About or Know?

• Artificial Sweeteners• Bird or Swine Flu• Blackberry Thumb Repetitive

Stress Injury (BTRSI)• Bottled vs. Tap water• Cell Phones• Farm vs. Wild Salmon• Fly to Argentina…• Heterocyclic Amines• High Fructose Corn Syrup• House Dust Mites• Mercury in vaccines

• Organic vs. Inorganic F/V• Pin Numbers• Power Lines • Second Hand smoke• Shake Weight• Sheen…• Taxes• Terrorism• Washing Hands• Woods

Distractions…

Alternative Medicine/Diet/Supplements Update from A-Z ... · Urol Clin N Am 2004;31:289-300....

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