What are we going to talk about:Staying healthy and optimized(CWI = “integrating mind & body for peakperformance”)• Staying alive –• Optimizing ability to think and perform whilestaying alive.– AND THAT MEANS:• Having adequate energy• Staying energetic and physically /sexually vigorous• (Can’t do love and work if you’re tired ordead.)
Why listen to the psychiatrist?• Because my patients care about the samethings as you do.• Because neuropsychiatric wellness,vascular, and nutritional health correlate withmost domains of “medical” wellness.• Guarding against– Loss of life– Loss of mental faculties• Somae & psyche = the fundamental balance.
Aging in America: The New Paradigm“Don’t put an Age Limit on your Dreams” – Dara Torres•The Oldest Swim Medalist in Olympic History•41 Year Old Dara Torres
Aging in America - 80 – The 3rdHalf of Life!www.bobdelmonteque.com
Bob Delmonteque – lived to 85• At 85 years of age.– Running marathons– Cycling 120 miles– Bench pressing over 250pounds.• Personal trainer to first 2sets of Apollo astroanauts• Personal trainer to JohnWayne, Errol Flynn, ClarkGable, & Marilyn Monroe
What can you do at 100?• Rita Levi Montalcini, MD• Nobel Prize – Medicine 1986• Birthday – April 18, 1909• “At 100, I have a mind that issuperior – thanks toexperience – than when Iwas 20.”• “Above all, don’t fear difficult moments. Thebest comes from them.”
Common neuropsychiatric(& MEDICAL) problems• Cognitive decline and senility (sneaks up on you)• Lack of mental (& physical) vitality• Sleep problems - from 1/3rdto 1/8thof thepopulation• Stress• Attentional Difficulties• If it’s bad, it’s linked to oxidative stress– PSYCH: Depression, anxiety, autism, ADHD, bipolar disorder andschizophrenia)– MEDICAL: Alzheimer’s, Parkinson’s, pain & arthritis
The Cognitive ContinuunDecline vs. Dementia• One study 403 randomly subjected subjects 67 – 78 yoa–38.4% - age-associated memoryimpairment.– 24.4% women, 30.1% men fulfilled ageing associated cognitive decline.• Hanninen T et al. Prevlaence of ageing-associated cognitive decline in anelderly population. Age Ageing. 1996 May;25(3):201-5• British study – 15,051. Prevalence of cognitiveimpairments was 18.3% (95% CI). (MMSE 23/24)– Rait G et al. Prevalence of cognitive impairment: results from the MRC trialof assessment and management of older people in the community. Ageand Ageing 2005;34:242-248.
More studies• 1/3rdof individuals in 131 eligible subjects inAustralia, age 70 – 79, community-dwelling metcriteria for “Cognitive Impairment No Dementia”(CIND).– Low, L-F, Brodaty H, et al. The prevalence of ‘cognitive impairment nodementia’ in community-dwelling elderly: a pilot study. Australian and NewZealand Jrnl Psychiatry 204;38:725-731.• “Oxidative damage occurs in the brain of subjectswith mild cognitive impairment, suggesting thatoxidative damage may be of the earliest events inthe onset and progression of Alzheimer disease.”– Keller JN et al. Neurology. 2005 Apr 12;64(7):1152-6
1997 study - changes in memory between 35-80yoaBurke DM, Mackay DG. Memory, language, and ageing. Philos Trans RSoc Lond B Biol Sci. 1997 Dec 29;352(1363):1845-56.
Salthouse TA. When does age-related cognitive decline begin? Neurobiol Aging2009 April 30 (4):507-14.
The majority – senile senescencemild cognitive• If you don’t die of heart disease or cancer, youwill suffer from senile senescence (to varyingdegrees).• But you can intervene in the process – you canchange the natural history.• LIEESTYLE INTERVENTION (diet + exercise =stress management) + SELECTIVESUPPLEMENTATION is a proactive, preventiveprogram that you can follow.
The Doc Cady “Candy Bar a Day”Weight Loss Program• 1 lb. of fat = 3,500 kcal (“calories”)• 3,500 / 7 = 500 calories per day– You need to not eat’em, or burn’em• Starving yourself slows your metabolism down, and youlose muscle mass– Therefore: reduce 250 calories; burn 250 calories• 250 calories = no candy bar, or “NO” to 1 & ½Cokes• 250 calories = ½ - ¾ hour on treadmill• NET = 500 calories per day, or 1 lb. lost perweek
One problem…• It doesn’t work!• It’s the INSULINRESPONSE.• RX: EAT LESSCARBS ANDSUGAR!!!
Glycemic index• A measure of how fast acarbohydrate triggers a rise incirculating blood sugar.• The higher the number, the greaterthe blood sugar response.
The horrifying facts about the foodsyou eat (and think are safe)(FOOD)•Tofutti•Glucose•French bread•Instant rice•Baked potato•Rice cakes (jelly beans)•Cheerios•Table sugar (sucrose)•Spaghetti, white•Spaghetti, protein enriched(glycemic index)11510095908577/8074644127
H - 33Doc Cady “Candy Bar a Day”program FLAWS:• Not all calories from food do the samething to your body.• Doesn’t account for thyroid or thyroidresistance.• Only focuses on WEIGHT LOSS, and notOPTIMUM HEALTH• Virtually impossible to “diet your way toweight loss.”– Needs diet AND exercise
…low levels of the antioxidant vitamins (Vitamins A, E, and C)may increase risk for several chronic diseases. Most people donot consume an optimal amount of all vitamins by diet alone.Pending strong evidence of effectiveness from randomized trials,it appears prudent for all adults to take vitaminsupplements.
Antioxidant (& other)targets andmeasurements(c) 2013 Louis B. Cady, M.D. - allrights reserved
(c) 2013 Louis B. Cady, M.D. - allrights reservedRamanshift
Antioxidants and carotenoids1) Carotenoids ID’ed 1992. Five important in human diet:alpha and beta carotene, lycopene, lutein zexanthin –found in blood and important in human health.– Khachik F et al. Separation and quantification of carotenoids in human plasma.Methods Enzymol. 1992;213:205-19.1) Carotenoids are POTENT ANTIOXIDANTS. Carotenoidmolecules can sustain 20 free radical hits before beingconsumed. If they are in skin, then they are in everyother cell of the body.– Tsuchiya, M et al. Antioxidant activity of alpha-tocopherol, beta carotene, andubiquinol in membranes:cis-parniaric acid-incorporated liposomes. MethodEnzymol. 1994; 234:371-83.– Tsuchiya M et al. Antioxidant radical-scavenging activity of carotenoids andretinoids compared to alpha-tocopherol. Methods Enzymol. 1992; 213:460-72.
Blue photons into hand… green photos out of handCounted by detector, computation by computer…= skin carotenoid scoreF D C B A
The options$25No pain! Results in 90 seconds$246PAIN! Wait 3 weeks.Go back to yourdoctor.$303Wallet pain! Wait 3 weeks.Go back to yourdoctor.Oxidative stress analysis - www.gdx.net
What to do??(c) 2013 Louis B. Cady, M.D. - allrights reserved
WILL an apple a day keep the doctoraway?• Liu S, et al. Intake of vegetables rich in carotenoids and risk of coronary heart disease inmen: The Physician’s Health Study. Int. J Epidemiol. 2001 Feb;30(1):130-5.• Findings adjusted for age, randomized treatment,BMI, smoking, alcohol intake, physical activity, DMhistory, HTN history, high cholesterol, use of(conventional) MVI’s..• 2.5 servings/day of vegetables had a“RR (relative risk) of 0.77” for CAD vs.men in lowest category– (<1 serving per day)
• “It is concluded thatadministration of antioxidantscould reduce the incidence ofbrain tumors and probably othertypes of cancer.”• - Shewelta SA , Sheikh, BY Curr Drug Metab. 2011Jul;12(6):587-93. (Dept.of Biosciences & Technology,Alexandria University, Egypt.)
15,318 US adults in 3rdNational Health and NutritionExamination Follow-up study. (Different lifestyles and health riskfactors were accounted for in the study)“serum alpha-carotene concentrationswere inversely associated with risk ofdeath from all causes, CVD, cancer,and all other causes[sic].”
Epidemiology of Vascular Ageing (EVA study)Total plasma carotenoids are inversely related to mortality (Br J Nutr, Jan2009, Akbaraly TN, et al• Study N=1389– Age range = 59 – 71 years; 9 years duration; 6 follow-ups• Findings:– For men - 2.94X higher relative riskof mortality of being in lowestquintile compared to highest quintile.– “The present study suggests that total plasmacarotenoid levels could be a health indicator inelderly populations.”
Lipid peroxidation, antioxidant status& survival in institutionalized elderly• Plasma MDApredicted mortality– (independently of all variables)• B-carotene and alphatocopherol wereindependentlyassociated withsurvival.Huerta JM et al. Free Radical Research2006, vol 40, no 6. pp 571-578.
Multiple lines lines of evidence indicate thatoxidative stress not only strongly participates inan early stage of Alzheimers disease prior tocytopathology, but plays an important role ininducing and activating multiple cell signalingpathways that contribute to the lesion formationsof toxic substances and then promotes thedevelopment of Alzheimers disease.
Adult ADHD and antioxidant status• Selek S et al. Evaluation of total oxidative status in adultattention deficit hyperactivity disorder and its diagnosticimplications. J. Psychiatry Research. 2012 Apr;46(4):451-5• CONCLUSION: “In ADULT ADHD,oxidative balance in impaired.High antioxidant levels may becompensatory against the oxidantincrease.”
what about otherthings besides carotenoidsand “Antioxidants”??B12, Magnesium, Selenium, Zinc, fishoil…
“Inadequate intakes may result in chronicmetabolic disruption, including mitochondrialdecay.”“[They] cause DNA damage, such as chromosomebreaks, in cultured human cells or in vivo.”“triage theory
The Physicians’ Health Study II• Take a multivitamin!CONCLUSIONS: “Daily multivitaminsupplementation modestly butsignificantly reduced the risk of totalcancer.”
Over 50% of the women in the Iowa studylived longer than the average lifeexpectancy38,000 White Women in IowaEarly results showed women who usedC, D, E, and Calcium had significantlylower rates of death
• Irritability• Apathy• Anxiety• Personality changes• Depression• Memory loss• Dementia• Subtle subclinicalcognitive impairment• Hallucinations• Violent behaviorSymptoms of B12 Deficiency• Diminished sense oftouch and pain• Clumsiness• Weakness• Pernicious anemia• Chronic fatigue• Tremors• GI problems• Peripheral neuropathyMental Physical
Your brain and B12• If you are in the bottom 1/3rdfor B-12levels….• SIX TIMES increase risk ofbrain volume loss (Odds ratio =6.17, 95% CI)– Vogiatzoglou A et al. Vitamin B12 status andrate of brain volume loss in community-dwellers.Neurology. 2008 Sep 9;71(11):826-32.– (107 volunteers aged 61-87 years of age)
Magnesium mementos• One of the first minerals to disappear with:– Processed food– Stress• Decreased by EtOH, caffeine, sodas, meds• Considered “anti-stress” mineral– Decreases cortisol (rel to sleep disruption)– Relaxes muscles, prevents cramps (sleepdisruption)– Decreases anxiety; improves sleep
Vitamins E & C Supplements Limit OxidativeBrain Cell Damage, Cognitive Dysfunction• Head, E, Christie L. (UC Irvine). Cognitive performance, dementia andDNA/RNA oxidative damage in the oldest old.” Poster 256 OxidativeStress and Synaptic Transmission, San Diego, 2007.• “The two antioxidant vitamins wereassociated with decreased oxidativedamage to brain cells in the frontalcortex. The researchers found that bettercognitive performances in elderly subjects isassociated with lower levels of oxidativeDNA & RNA damage in the brain…”
Vitamin B3 Restores Memory LossAssociated with Alzheimer’s Disease• Green K et al. (UC Irvine) “Oral Nicotinamide TreatmentInduces Ubiquitin-dependent degradation of phospho-tauand restores cognitive function in a mouse model ofAlzheimer disease.” Poster 157, Nov 4 at Alzheimer’sDisease and Other Dementias: Therapies II; San Diego2007• B3 given to rice BRED to develop plaques and tangles.• Mice that received this had lower levels of phosphorylatedtau.• “These findings suggest that Vitamin B3… might be a safeand effective therapy for people with Alzheimer’s disease.”
The Effects of high dose B vitaminson stress at work• 3 month, double blind, placebo control, randomized study– Measured: Personality, work demands, mood, anxiety, and strain• The vitamin B complex treatedgroup reported significantly lowerpersonal strain and a reduction inconfusion and depressed/dejectedmood after 12 weeks.Strough C et al. The effect of 90 day administration of a high dose vitamin B-coplex on work stress. Hum Psychopharmacol. 2011 Sept 8. doi10.1002/hup.1229 (Swinburne University of Techbnology – Hawhorn, Victoria,Australia.)
RESULTS:[Serris et al. Nutrition Journal 2012, 11:110]• Increased energy levels(p=0.22)•(most evident on women)• Enhanced mood (p=.027)• No significant negative effects
BRAIN SHRINKAGE…Smith AD, Smith SM, de Jager CA, Whitbread P, et al. (2010) Homocysteine-Lowering by B Vitamins Slows theRate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial. PLoS ONE5(9): e12244. doi:10.1371/journal.pone.0012244http://www.plosone.org/article/info:doi/10.1371/journal.pone.0012244CONCLUSIONS: “Theaccelerated rate of brainatrophy in elderly with MCI canbe slowed by treatment withhomocysteine-lowering B-vitamins.”
OK. It slows shrinkage. But are they sharper?[deJager CA et al. Int J Geriatr Psychiatry. 2012 June;27(6):592-600]“B-vitamins appear to slow cognitive and clinicaldecline in people with MCI.”
Reference: R2in Physician’s Desk Reference, 2013Cordyceps sinensisCs-4 Mushroom Mycelia Panax GinsengPharmanex Asian Ginseng Rb1 (Panaxginseng) Root Extract—a proprietaryginseng extract with a balance ofbiological activity not found in otherginseng extracts;Pomegranatea unique, patented extract fromPunica granatum.Proprietary and patent pending blend3 unique extracts
”Mitochondrial Dysfunction in the Elderly: Possible Role in InsulinResistance” Science 16 May 2003:Vol. 300. no. 5622, pp. 1140 – 1142MITOCHONDRIAL ACTIVITY DECLINES WITH AGE18~39864261~84- 40%
TARGET & RESET YOUTH GENE CLUSTERS77Old GeneExpressionYoung GeneExpressionTARGETOld GeneExpressionRESET1Transcriptional Biomarkers of Mitochondrial Aging and Modulation by CordycepsSinensis Cs-4. Gordon Research Conference, Biology of Aging, Determinants ofHealth-Span: From Cells to Humans, August 22-27, 2010. Les Diablerets ConferenceCenter, Les Diablerets, Switzerland.Column 3 shows how this productRESET 92% OF THEMITOCHONDRIAL GENESto their youthful state.92%
“Targeting Age-related gene expressionimproves mental and physical vitality”Ferguson SB SM et al. Paper presented at 1stWorld Congress on TargetingMitochondria, Strategies, Innovations & Clinical Applications. Berlin, German.November 18-19, 2010.• Human cognitive change trial most exciting.• Four groups, 10 per group, ages 28 – 50 years of age– Positive control group - took 200 mg Phosphatidylserine DHA, 300 mg Bacopa, and30 mg of Vinpocetine.– Vitality blend took 2,270 mg/day of CS4+ PG+ PGE– Placebo – monocrystalline cellulose, caramel color– No supplementation.• 6 Parameters measured and averaged to = the COMPOSITECOGNITION INDEX* (CCI): * from http://www.mybraintrainer.com– Three choice reaction time– Short term memory– Executive function– Information processing– Pattern recognition– Working memory.
BioGinkgo 27/7 (50:1)(EGb761 = standard. Composition is 26/6)• Comprised of 27% ginkgo flavonone glycosides and 7%terpene lactones– Typical is 22 – 27% flavonone glycosides– 5 – 7% terpene lactones• Two mechanisms of actions:– Gingko flavone glycosides – mainly anti-oxidant properties (free-radical scavenging comparable to Vitamin E and Vitamin C)– Anti-platelet effects• Ginkgolide B – a potent and long-lasting platet activating factor antagonist• Terpen lactones, ginkgolides, and bilobalide also = platelet activating factorantagnosits.• Drug interactions: do not use with anticoagulant, ASA daily, MAOinhibitor, allergic to ginkgo•
• aadsfasfdEGb761 is used in most trials. Dosages: 80 –720mg/dayMechanisms of action: increasing cerebralblood flow, antioxidant and anti-inflammatory effects, withantiplatelet effects attributed to flavoneand terpene lactones.(“Possible interactions with MAOI’s,alprazolam, haloperidol, warfarin, and nifedipinehave been reported.”)
Gingko – color commentary• 2,991 citations in PubMed as of 3 30 2013• Cognitive enhancement:– 34 outpatients with moderate cognitive impairments tx’ed withstandard extract of Ginkgo Biloba (EGb761) – 240 mg twice daily .Significant improvement in attention, memory, orientation, andvisual-spatial/executive functions as well as anxiety anddepression.”• Boiko AN et al. Zh Nevrol Psikhiatr Im S S Korsakova. 2013 – “Possibilities ofmedical correction of moderate cognitive impairment.”• In addition to cognitive effects:– Might be useful in patient with early diabetic nephropathy . Zhang Let al. Evid Based Complement Alternat Med. 2013– Anti-inflammatory on osteoarthritis of knee. Chen YJ et al. JOrthop Res. 2013 Mar 11.
How much insomnia?Buysse DJ. Insomnia. JAMA. 2013 Feb20;309(7):706-16• Prevalence is 10 – 20%–Approximately 50% of these have chroniccourse• Major risk factor for impaired function,developmental of other medical nadmental disorders, and increased healthcare costs.
• Mitochondrial diseases are due to impairment ofchemical reactions.• A reasonable theory is oxidative stress.• Few studies have actually been done on this.• Glutathione deficiency is known in mitochondrialdisease.• Biosynthesis of glutathione depends on cysteineavailability.• “Our findings reinforce the notions that inmitochondrial disease, oxidative stress isimportant and can be reduced byadministration of a cysteine donor.”