Be.-S.A.M. or B.-S.A.M:Best “Natural” Pills…
Mark A. Moyad, MD, MPHJenkins/Pokempner Director of CAM
Department of UrologyUniversity of Michigan Medical Center
1500 E. Medical Center DriveAnn Arbor, MI 48109-0330E-mail: [email protected]
Hobbies: NONE!(actually making Dr. Crawford look good)
SOME MOYAD RULES…1. You don’t have scurvy2. First Do No Harm (natural
pills)… to Heart3. More is NOT better-except
with exercise/lifestyle changes
PHASE 3-Supplements-Urology
• ATBC, CARET, AREDS2=Lung Ca
• B6, Mega-Dose, Vitamin (Rx)…=Nothing!
• Seleblat…NMIBC…=Nothing!.
• STEP and CAMUS=BPH/LUTS=Nothing!Moyad MA. CAM for Prostate & Urologic Health. 2014; Springer, NY. & Moyad MA. AUA Update Submitted.
SELECT
-35,000 healthymen
-300 sites
-125 millionDollars
-NO IMPACTON BLADDER CA.
-400 IU-Vitamin E Increased risk of Prostate Cancer…
-200 mcgSelenium =Nothing
FOLIC ACID PillsAnd Bladder Cancer?(Tu H, et al. Am J Clin Nutr 2018’107:208-216)..
P Vit E SEL E + Sel
TOTALPCa
1.0 1.17(.008)
1.09 1.05
Gleason Score7 or More
1.0 1.16 1.21 1.23(.08)
WHAT IF SELECT…?
Klein E, et al al. JAMA 2011; 306: 1549-1556Tu H, et al. Am J Clin Nutr 2018;107:208-216.
.
FOLIC ACID?Bladder Ca?
VIT. D TRIAL=2019(& Omega-3)
• No Impact on preventing Cancer/CVD
• N=25,871, 5.3 years, 2000 IU
• STONES???…HR=1.12 & P=0.08
Manson JE, et al for VITAL Research Group. N Engl J Med 2019;380:33-44.
Calcium/Vitamin D versus Resistance Exercise
• 18-month random trials (n=180 men, 50-79 yrs )
• 3 days/week=2-3% increase in BMD
• “…providing additional calcium-D3 to these replete men did not enhance the osteogenic response.”
.
Kukuijan S, et al. J Clin Endocrinol Metab 2011;96:955-963
HEART HEALTHY=
Bladder Healthy=Kidney Healthy=Prostate Healthy= Sexual Health…
BLAH BLAH BLAH…
ALL HEALTHY!(FIRST DO NO HARM)
Moyad MA. The Supplement Handbook, Random/Rodale2018.. PAGE 34.
Statin Scares/Conspiracy(COST?)
ATORVASTATIN GENERIC
FLUVASTATIN GENERIC
LOVASTATIN GENERIC
PITAVASTATIN GENERIC?????
PRAVASTATIN GENERIC
SIMVASTATIN GENERIC
ROSUVASTATIN GENERIC NOW!
AHA Statin Safety-2019
• <0.1%=Serious Muscle Injury• Hepatotoxicity=0.001%
Blah Blah Blah…..NOCEBO!
Bottom Line=Primary prevention trial of lifestyle versus statin?
Newman CB, et al. AHA Statement. Arterioscler Thromb Vasc Biol. Released Dec 10, 2018.
Statins-Conspiracy?CONCLUSION!!!
• �When used for primary prevention, statins are associated with lower rates of all-cause mortality, major vascular events, and revascularizations compared to placebo.�
• -18 Randomized trials, n=56,943, Age=57(28-97)
Taylor FC, et al. JAMA 2013;310:2451-2452.
NMIBC & Statins(Univ Toronto & )
• Retrospective population-based cohort• N=13,811 dx w/NMIBC (34% statins)• No impact but better overall survival
• Bottom Line=First Do No Harm
Richard PO, et al. Urol Oncol 2017;35:342-348..
Statins-ASCO-GU-2015ADT + Statins + Harvard/Canada
• “…statin use at the time of ADT initiation was associated with a sign increase in TTP on ADT even after adjusting for established prognostic factors.” (n=926)
• ADT following primary or salvage RT- “statin use was associated with improved overall and prostate cancer-specific survival & improved QL.” IAD-”more off trtintervals & longer off-trt.”(n=1364)
Harshman LC, et al. J Clin Oncol 2015; 33: Abstract 148, March 1 Supplement. & Hamilton RJ, et al. Abstract 145.
Pleiotropic Properties of Statins
• Inhibit thrombotic process (surgery)• Inhibit tumor cell proliferation• Inhibit angiogenesis• Modulate immune responses• Reduce inflammation• Reduce Inflammatory markers
• Improve vascular endothelium function
• Stimulate bone growth/prevent bone loss
• Reduce oxidative stress• Modulate smooth muscle cell
proliferation• Stabilize plaques• Enhance fibrinolysis• DHEA? (Intratumoral?)• VS. DIET/LIFESTYLE??
Stamm JA, Ornstein DL. Oncology 19(6):739-754, May, 2005. & Harshman LC, et al. JAMA 2015;1:495-504.
Pca & Aspirin-2015 Meta-Analysis
• 39 Studies (20 CC & 19 Cohort..>108,000 Cases)
• “The present meta-analysis provides support for the hypothesis that aspirin use is inversely related to Pca incidence and Pca-specific mortality.”
• NOW REDUCE/PHS!!
Liu Y, et al. BMC Medicine 2015;12:55.
Finnish RP Cohort 2019 &Univ WI 2019 Study
• N=14,424 Men w/Pca• HR=0.70 (lower risk of ADT and Pca Death)
• Natl VA Database (N=87,346)• Men on ADT improved Pca & OS!
Joentausta RM, et al. Prostate 2019; Released January 16.Anderson-Carter I, et al. Urol Oncol 2019;37:130-137.
Aspirin & Physicians’Health Study
• N=22,071 Male Physicians (1982-2009)-27 yrs!!!• >3 Tablets/week• After dx 27% reduction mortality!
Bottom Line=No Impact on incidence!
Allard CB, Downer MK, Preston MA, et al. J Clin Oncol 2016;Suppl 2S; abstract 306.
A=ASPIRIN (baby?)(ASPREE Trial-Breaking News!)
ASPREE Trial (aspirin in reducing events in the elderly)
• Primary Prevention (100mg Enteric-Coated)
• No Benefit (after median 4.7 years)
• Higher Risk of Major Hemorrhage• MEDIAN AGE=74 YEARS OLD/HEALTHY (n=19,114)
ASPREE Investigator Group. N Engl J Med 2018;379:15009-1518. OCTOBER 18th!
ASPREE Trial (THE REAL STORY!!!)
• MEDIAN AGE=74 YEARS OLD/HEALTHY (n=19,114)
• “All-cause mortality and cancer-related mortality in the trial population were 32% and 49% of the rates in the general population, respectively.” (food-salicylates)
ASPREE Investigator Group. N Engl J Med 2018;379:15009-1518. OCTOBER 18
Better Numbers + Age=No Aspirin Needed.
www.cvriskcalculator.com
(AHA, ACC, USPSTF-2018)
Pca & Metformin-New 2015 Meta-Analysis
• 21 Studies• “Results suggest that metformin use appears to be
associated with a significant reduction in cancer risk and BCR of prostate cancer, but not in all-cause mortality of patients with prostate cancer.”
Yu H, et al. PLoS One 2014 Dec 29, 9(12):e116327.
Metformin (850 mg bid + Low-Glycemic/Cal Diet + Exer)
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)
Nobes JP, Langley SE, Klopper T, et al. BJU Int 2012;109:1495-1502.
Metformin & Phase 3 Breast Cancer Trial-NCIC CTG MA.32
• N=Nondiabetic=492 (52 yrs, BMI=27)...6-months• Weight= -4 lbs vs. +1.5 lb• Glucose= -4%• Insulin= -11%• Leptin=-20%• hs-CRP= -7%• 95.5 mg/dL=BASELINE!!!
Goodwin PJ, et al. J Natl Cancer Inst 2015;107:doi 10.1093/jnci/djv006
Phase 3-Polyp Recurrence Trial-JAPAN-DOSE=250 mg!!!
• NON-DIABETIC=100 mg/dl (n=151, age =65, BMI=23!
• After-1 year...40% Reduction (p=0.02) vs. Placebo...Adenoma (& total polyps)
• Side effects same as PLACEBO!!!
Higurashi T, et al. Lancet Oncol 2016;17:475-483.
METFORMIN-Final Thoughts
• 500-2000 mg (850 mg BID-Most Common??)….250 mg?• After meals=YES!!! • Soft Stool/Diarrhea• Contrast/ Renal/Liver Insufficiency=NO!• Deficiency B12 & MagnesiumRothermundt C, et al. Eur Urol 2014;66:468-474. & Goodwin PJ, et al. J Natl Cancer Inst 2015;107: epub March 4, 2015. & Moyad MA, Vogelzang NJ. Asian J Androl 2015; February 3, epub ahead of print.
Metformin(850 mg BID)
• Diabetes Prevention (n=3234 high-risk)
• -31%=Metformin
• -58%=intensive lifestyle changes!!!
• Prevent Diabetes=Prevent CANCER?!Diabetes Prevention Program Research Group. Lancet 2009;374:1677-1686. Knowler WC, Barrett-Connor E, Fowler SE, et al. N Engl J Med 2002;346:393-403.
Infantile Hemangioma (IH)
• Most common benign tumors of infancy
• Main indication for treatment=life threatening
• WHAT IS FIRST-LINE TREATMENT?
Leaute-Labreze C, et al. Lancet 2017;390: 85-94.
Infantile Hemangioma (IH)
Leaute-Labreze C, et al. Lancet 2017;390: 85-94. & Novoa M, et al. Cochrane Database Syst Rev 2018;4:CD006545.
PROPRANOLOL!!!WHAT THE _____!(2-3 mg/kg/day_
Melanoma?
• N=53; 80 mg daily (n=19 vs n=34)• 3-years DFS 84.2% vs. 58.8%(15.% vs. 41.2% progression)
• HR=0.18 (95% CI 0.04-0.89; p=0.03)
• Bottom Line=COME ON MAN!
De Giorgi, V, et al. JAMA Oncol 2018;4:e172908.
Prostate Cancer?
• Prevents proliferation?• Induced cell apoptosis?• Tumor growth suppression?
Bottom Line=?? Nebivolol? BP & URO!!!(Who needs pills when you have…)
Brohee L, et al. Sci Rep 2018;8L1):7050. &Itesako T, et al. Urology 2018;122:165-168.
Sharp RP, Gales BJ. Ther Adv Urol 2017;9:59-63.
BREAKING NEWS!!!
American Academy of Neurology (AAN) Guidelines 2018-MCI
Petersen RC, et al. Neurology. Dec, 27, 2017;DOI: 10.1212/WNL.0004826.Horder H, et al. Neurology. 2018 (March 14). PROTEIN???
CRF and All-Cause Mortality. N=122,007…CLEV CLINIC…ETT1.1 MILLION PATIENT-YEARS OF OBSERVATION!!!!!!!!!!!!!!
Mandsager K, et al. JAMA Network Open 2018; 1: e183605…Oct 19, 2018.
SOME MOYAD RULES…1. You don’t have scurvy2. First Do No Harm (natural
pills)3. More is NOT better-except
with exercise/lifestyle changes
