Vitamins and Antioxidants implication in frailty prevention Tamas - - PowerPoint PPT Presentation

Vitamins and Antioxidants implication in frailty prevention

Tamas Fulop M.D., PhD Université de Sherbrooke

CONFLICT OF INTEREST DISCLOSURE

I have the following potential conflict(s) of interest to report

• Consultation fee from Eisai and Co, Japan

Definition of frailty

There is no universally accepted definition of frailty:

• Depends on whether we consider populations, individuals, research, clinical

levels.

What is agreed by most:

• A geriatric syndrome: multifactorial
• cumulative declines and decreased reserves in multiple physiological and
• rgan systems: homeostenosis.
• physiologic dysregulation involves multi-organ systems including the

musculoskeletal, immune, endocrine, hematologic, and cardiovascular systems: the sum is more important than the nature of each

• Results in vulnerability to adverse outcomes: e.g. Falls, death, dependence
• Triggered or revealed by minor stressor events, stimuli
• Age plays the major role: prevalence  with age

Loss of function

Graphic showing the difference between successful aging and frailty

http://www.clinicalgeriatrics.com/article/frailty-multimorbidity-elderly-shift-management-approach#sthash.IfxmHZiW.dpuf

• The most used criteria to characterize the phenotype of frailty as

clinical syndrome are:* : – Loss of wait: self reported – Weakness: grip strength – Exhaustion: self reported – Slowed walking speed: measure of walk speed – Low physical activity: self reported Frailty : presence of at least 3 of these 5 characteristics

• Fried, Tangen, Walston et coll., J Ger Med Sci, 2001

Operationalization/Diagnosis of frailty

The cumulative frailty index (accumulation of deficits):*

• disability,
• diseases,
• physical and cognitive impairments,
• psychosocial risk factors, and
• Geriatric syndromes (eg, falls, delirium, and urinary incontinence)

*Mitnitski AB, et al. Scientific World Journal 2001;1:323–36.

Clegg et al, Lancet 2013, 381:752

Fried ried's 's scien scientifi tific c exp xplana lanation tion of

• f th

the c e cycle of le of fr frailty ailty

http://www.hopkinsmedicine.org/hmn/s02/feature.

Kanapuru and Erschler, Am J Med. 2009, 122:605

Pathophysiologic Model for Adverse Outcomes in Older Adults

Aging  Free radicals Senescent cells Shortened telomeres DNA damage Disease Depression Cancer Chronic Infection Cardiovascular disease Diabetes/Obesity

Frailty Disability Disease Death

CRP IL-6 IGF-1 DHEA-S Cortisol

Activation of Inflammation Neuroendocrine Dysregulation Anorexia ? Anemia Sarcopenia Osteoporosis Hyperglycemia  Clotting

Triggers Physiology Outcomes Gene Variation

IL-6 DHEA-S Cortisol

Modified after Walston et coll., 2006

IL-6 and Multisystem Dysregulation

IL-6

Lean body mass Anemia Polyclonal expression & autoantibodies Osteoporosis Localized CNS inflammation HPA axis activation

Frailty and inflammation/immune-aging markers

IL-6

 ASSOCIATED to atherosclerosis, osteoporosis, sarcopenia to functional decline and all cause mortality PREDICTING steeper functional decline during a follow up of 3.5 years (Ferucci et al, JAGS, 2002, 50:1941) measured by:  decreased muscle strength and power and slowed walking speed  two central components of the frailty syndrome.  In Vitro: PBMC stimulated by LPS produced higher IL-6 in frail than Non-frail community dwelling subjects

IL-6 levels: independently associated with frailty

Rutenberg, A.D., Experimental Gerontology (2017), http://dx.doi.org/10.1016/j.exger.2017.08.027

Putative alterations of major biological parameters AGING

FRAILTY

LOW GRADE INFLAMMATION HIGH GRADE INFLAMMATION NO LIPID ALTERATIONS LIPID ALTERATIONS IMMUNE RESPONSE:  IMMUNE RESPONSE:    HORMONES: LOW HORMONES: VERY LOW NO ANEMIA ANEMIA NO NUTRITIONAL ALTERATIONS NUTRTITIONAL ALTERATIONS CHRONIC VIRAL INFECTION+(?) CHRONIC VIRAL INFECTION++(?)

Aging Aging+ + syndr syndrome

• me (=b

(=biolo iologi gical cal age) ge)

Fulop et al. 2010

Heuberger RA, JNGG, 2011, 30:315

The etiology and progression of clinical frailty in the older adult

Dorner et al. The Journal of Nutrition, Health & Aging; Volume 18, Number 3, 2014; 264

The immune system and oxi-inflamm-ageing

M.E. Bauer, M.D.l. Fuente / Mechanisms of Ageing and Development 158 (2016) 27–37

Frailty

• P. Soysal et al. / Maturitas 99 (2017) 66–72

Semba et al. Am J Med. 2007 Dec; 120(12): 1084–1089.

Grouped-time Multivariate Cox Proportional Hazard Models for Demographic and Health Characteristics and Incidence of Severe Walking Disability in the Women’s Health and Aging Study I (N = 545)

Oxidative parameters increased in frailty!!!

Nutrition du sujet âgé, Université Médicale virtuelle francophone

• P. Soysal et al. / Maturitas 99 (2017) 66–72

Age Age- and and se sex-adjusted adjusted le levels els of

• f vi

vitamin tamin E acc accor

• rding

ding to to fr frail ailty ty sta

• status. T
• tus. The unit

he unit of

• f measur

measure e for

• r vi

vitamin tamin E (y a (y axis) is xis) is μmol/L /L

Ble et al. Journal of Gerontology: MEDICAL SCIENCES, 2006, Vol. 61A, No. 3, 278–283

AA is at the crossroads of biological aging, intercepting immunosenescence, inflamm-aging, and oxidative stress (free radical theory of aging), with a potential role in the onset of age- related diseases and frailty trajectories

Monacelli et al. Nutrients 2017, 9, 670

Michelon et al. Journal of Gerontology: MEDICAL SCIENCES 2006, Vol. 61A, No. 6, 600–607

WHAS I study: women 70-80 years: n=754 * * * * *

Michelon et al. Journal of Gerontology: MEDICAL SCIENCES 2006, Vol. 61A, No. 6, 600–607

Michelon et al. Journal of Gerontology: MEDICAL SCIENCES 2006, Vol. 61A, No. 6, 600–607

Michelon et al. Journal of Gerontology: MEDICAL SCIENCES 2006, Vol. 61A, No. 6, 600–607

Independently of the adjusted model the OR, was always higher for those with low micronutrient concentrations * *

Yannakoulia et al. M E T A B O L I S M C L I N I C A L A N D E X P E R I M E N T A L 6 8 ( 2 0 1 7 ) 6 4 – 7 6

Yannakoulia et al. M E T A B O L I S M C L I N I C A L A N D E X P E R I M E N T A L 6 8 ( 2 0 1 7 ) 6 4 – 7 6

Semba et al. Journal of Gerontology: MEDICAL SCIENCES 2006, Vol. 61A, No. 6, 594–599

Semba et al. Journal of Gerontology: MEDICAL SCIENCES 2006, Vol. 61A, No. 6, 594–599

From 463 studied 205 became frail

Semba et al. Journal of Gerontology: MEDICAL SCIENCES 2006, Vol. 61A, No. 6, 594–599

Dokuzlar et al. North Clin Istanb 2017;4(1):22–28

Bartali et al. Arch Intern Med. 2006 November 27; 166(21): 2335–2340

Bartali et al. Arch Intern Med. 2006 November 27; 166(21): 2335–2340

Yannakoulia et al. M E T A B O L I S M C L I N I C A L A N D E X P E R I M E N T A L 6 8 ( 2 0 1 7 ) 6 4 – 7 6

Yannakoulia et al. M E T A B O L I S M C L I N I C A L A N D E X P E R I M E N T A L 6 8 ( 2 0 1 7 ) 6 4 – 7 6

Yannakoulia et al. M E T A B O L I S M C L I N I C A L A N D E X P E R I M E N T A L 6 8 ( 2 0 1 7 ) 6 4 – 7 6

How does sarcopenia develop in older patients and how is it best managed?

http://www.arthritis-rheumatism.com/the-rheuma-muse/sarcopaenia/

Comparison Comparison of

• f the

the fr frequ equenc ency y of

• f sar

sarcop copenia enia and and dyna dynapen penia ia in t in the he pa patients tients acc accor

• rding

ding to vi to vitamin tamin B12 B12 le levels els

Bulut et al. Exp. Ger. 2017, 95, 136

Welsh AA. Proceedings of the Nutrition Society (2014), 73, 16–33

Yannakoulia et al. M E T A B O L I S M C L I N I C A L A N D E X P E R I M E N T A L 6 8 ( 2 0 1 7 ) 6 4 – 7 6

L.M. León-Muñoz et al. / JAMDA 15 (2014) 899e903 Mediterranean Diet Adherence Screener (MEDAS) score and the Mediterranean Diet Score, also known as the Trichopoulou index

Ng et al. The American Journal of Medicine, Vol 128, No 11, November 2015; 1225

Summar Summary In In tot total t al these hese sug suggest gest, , in accor in accordance wit dance with h pr previous vious findings, tha findings, that a t a high high-qua quality lity diet with diet with food

• ods

s ric rich in a h in antio ntioxida xidant nt nutrients nutrients and and wit with h suf sufficient ficient ener energy y intak intake, and adequa e, and adequate and t te and timel imely y intak intake of e of pr protein

• tein ar

are e impor important tant in r in reducing educing the the ris risk of k of fr frailt ailty. It It is is dif difficult t ficult to

• est

establish w blish wha hat t is is the caus the cause e and w and wha hat i t is s the ef the effect. If

• ect. If

nutrit nutritiona ional l factor actors s ar are associa e associated ted wit with h fr frailty ailty, is , is tha that becau t because these se these factor actors s ar are contr e contributing ibuting to to fr frailt ailty, or , or because people tha because people that ar t are fr e frail ail reduce educe their their intak intake? e? So So whilst hilst the e the evidence vidence we ha e have e is is sug suggest gestiv ive, it e, it cannot det cannot deter ermine mine conc conclusiv lusivel ely y the impact the impact of

• f nutr

nutrit ition ion on fr

• n frailt

ailty, , and mor and more st e studies udies ar are e needed needed to fur to further ther under underst stand and the pot the potential ential r role of

• le of nutr

nutrit ition ion in t in the he pr prevention, ention, post postponement ponement and r and rever ersal sal of

• f fr

frailt ailty. . Ho However er, , this this should should not not in an in any w y way deter ay deter fr from the

• m the pr

provision vision of

• f diets

diets to to elder elderly y tha that t ar are both s e both suf ufficient in ener ficient in energy y and pr and protein

• tein and tha

and that s t suppl upply y impor important tant micr micronutr

• nutrients

ients. . No No supplement supplementation tion of

• f micr

micronutr

• nutrients

ients when hen ther there is e is no def no deficienc iciency! y!

Conclusion  Frailty may be the expression of a THRESHOLD when the physiological reserve is critically decreased by aging  aging+ syndr  Frailty is more the result of the SUM of altered systems than abnormalities in a particular system: IMMUNE + ENDOCRINE+ MUSCLE + NEURONAL  Frailty can be an expression of the BIOLOGICAL age rather than the chronological age, however causal relationships between IL-6, TNF-alpha and

• ther inflammatory markers and frailty have yet to be proven

 No biological markers can currently be associated directly to frailty  No nutritional interventions by Antioxydants OR Vitamins are efficient BUT Mediterranean diet could be

The Tower of Babel by Pieter Brueghel the elder (1525-69). He conceived it as an allegory of pride and human frailty.

Thank you!