Sains Malaysiana 48(3)(2019): 613–619
http://dx.doi.org/10.17576/jsm-2019-4803-14
Blood
Inflammatory Markers, Anabolic Hormone, Vitamin D and L-Carnitine Status
According to Frailty Status among Older Adults
(Penanda
Inflamasi Darah, Hormon Anabolik, Vitamin D dan Status L-Karnitin menurut
Status Keuzuran dalam Kalangan Warga Emas)
MANAL BADRASAWI1,2, SUZANA SHAHAR1*, NOR FADILAH RAJAB3 & DEVINDER KAUR AJIT SINGH4
1Dietetic, Programme
and Centre for Healthy Aging and Wellness, Faculty of Health Sciences, Universiti
Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Federal
Territory, Malaysia
2Nutrition
and Food Technology, Faculty of Agriculture, An-Najah National University, Palestine
3Biomedical
Programme and Centre of Healthy Aging and Wellness, Faculty of Health Science,
School of Healthcare Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda
Abdul Aziz, 50300 Kuala Lumpur, Federal Territory, Malaysia
4Physiotherapy
Programme and Centre for Rehabilitation and Special Needs, Faculty of Health
Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300
Kuala Lumpur, Federal Territory, Malaysia
Diserahkan: 24 April 2018/Diterima: 9 Januari 2019
ABSTRACT
Frailty is associated with functional decline and reduced ability
to cope with physiological challenges. The pathophysiological changes in
frailty include inflammation, endocrine disturbances, neuromuscular and immune
dysfunction. However, comprehensive information on the relationship between
biological markers and frailty is scarce. We aimed to determine the
relationship between selected biomarkers and frailty among Malaysian older
adults. In this cross sectional study, 600 community dwelling older adults were
randomly selected from ten different areas in Klang Valley. A total of 382
participants met the inclusion criteria and consented to the study. Out of
these, a subsamples of 91 participants were selected for biomarkers analysis.
Frailty was defined using Fried’s criteria. Fasting blood glucose, lipid
profile, albumin, selected frailty biomarkers including IL-6, TNF-
alpha and IGF-1 and vitamin D together with free L-carnitine and
acetyl L-carnitine were analysed. The results showed a significantly higher
level of serum IL-6 and TNF-α among participants
classified as frail as compared to pre-frail and robust (p<0.05). With respect to nutritional
biomarkers, binary logistic regression showed that vitamin D deficiency is
associated with three times higher risk of frailty (p<0.05). There
was no significant relationship between blood L-carnitines and frailty. Further
research is required to explore the relationship between L-carnitine and
frailty using different parameters involved in L-carnitine homeostasis such as CPTII enzyme and OCTN2 mutation. In conclusion, frailty
was associated with increased level of inflammatory markers and vitamin D
deficiency. It is empirical to promote healthy lifestyle or disease management
to reduce inflammation and increase vitamin D status as one of the frailty
prevention action plan among older adults.
Keywords: Anabolic hormone; frailty biomarkers; inflammatory
mediators; L-carnitine; vitamin D
ABSTRAK
Keuzuran adalah berkaitan dengan kemerosotan status kefungisan dan
keupayaan dalam menangani cabaran fisiologi. Perubahan patofisiologi keuzuran
termasuklah ketakfungsian ototneuro, ketakupayaan fungsi imun, inflamasi dan
gangguan endokrin. Namun begitu, tidak banyak penyelidikan yang mengkaji
hubungan antara petunjuk biologi dan keuzuran secara menyeluruh. Oleh itu,
kajian ini menentukan hubungan antara petunjuk biologi tertentu dan status
keuzuran dalam kalangan warga emas. Seramai 600 orang warga emas daripada
komuniti dipilih secara rawak dari 10 buah kawasan di Lembah Klang. Seramai 382
peserta memenuhi kriteria kajian dan bersetuju mengambil bahagian. Seramai 91
subjek dipilih daripada sampel keseluruhan untuk analisis petunjuk biologi.
Keuzuran didefinasikan daripada kriteria Fried. Petunjuk biokimia keuzuran yang
dikaji termasuk IL-6, TNF-
alfa dan IGF-1 serta vitamin D, bersama-sama dengan L-karnitin
bebas dan asetil L-karnitin dianalisis. Keputusan menunjukkan aras plasma darah
IL-6 dan TNF-α adalah lebih tinggi secara signifikan dalam
kumpulan uzur berbanding, prauzur dan robus (p<0.05). Berhubung dengan petunjuk biologi pemakanan,
analisis logistik binari menunjukkan kekurangan vitamin D berkaitan dengan
risiko keuzuran sebanyak tiga kali ganda (p<0.05). Tiada hubungan
signifikan antara L-karnitin dalam plasma darah dengan keuzuran, oleh itu,
penyelidikan lanjut diperlukan untuk mengkaji hubungan antara homeostasis
L-karnitin seperti enzim CPTII dengan mutasi OCTN2.
Kesimpulannya, keuzuran dikaitkan dengan peningkatan tahap penanda inflamasi
dan kekurangan vitamin D. Terdapat keperluan untuk meningkatkan strategi
promosi gaya hidup sihat atau pengurusan penyakit untuk menurunkan tahap
keradangan dan meningkatkan aras vitamin D bagi mencegah keuzuran dalam
kalangan warga emas.
Kata kunci: Keuzuran; L-karnitin; pengantara inflamasi; petunjuk
biologi; vitamin D
RUJUKAN
Almeida, O.P., Norman, P.E., van Bockxmeer,
F.M., Hankey, G.J. & Flicker, L. 2012. CRP 1846G A polymorphism increases
risk of frailty. Maturitas 71(3): 261-266.
Annweiler, C., Bataille, R., Ferrière, N.,
Douillet, D., Fantino, B. & Beauchet, O. 2011. Plasma beta-2 microglobulin
as a marker of frailty in older adults: A pilot study. The Journals of
Gerontology Series A: Biological Sciences and Medical Science 66(10):
1077-1079.
Ble, A., Cherubini, A., Volpato, S., Bartali,
B., Walston, J.D., Windham, B.G. & Ferrucci, L. 2006. Lower plasma vitamin
E levels are associated with the frailty syndrome: The InCHIANTI study. The
Journals of Gerontology Series A: Biological Sciences and Medical Sciences 61(3):
278-283.
Brass, E.P., Adler, S., Sietsema, K.E., Hiatt,
W.R., Orlando, A.M. & Amato, A. 2001. Intravenous L-carnitine increases
plasma carnitine, reduces fatigue, and may preserve exercise capacity in
hemodialysis patients. American Journal of Kidney Diseases 37(5):
1018-1028.
Byard, R.W. 2015. Frailty syndrome-medicolegal
considerations. Journal of Forensic and Legal Medicine 30: 34-38.
Calabrese, V., Stella, A.M.G., Calvani, M. &
Butterfield, D.A. 2006. Acetylcarnitine and cellular stress response: Roles in
nutritional redox homeostasis and regulation of longevity genes. Journal of
Nutritional Biochemistry 17(2): 73-88.
Campos, Y., Arenas, J., Cabello, A. &
Gomez-Reino, J.J. 1995. Respiratory chain enzyme defects in patients with
idiopathic inflammatory myopathy. Annals of the Rheumatic Diseases 54(6):
491-493.
Cavallini, G., Caracciolo, S., Vitali, G.,
Modenini, F. & Biagiotti, G. 2004. Carnitine versus androgen administration
in the treatment of sexual dysfunction, depressed mood, and fatigue associated
with male aging. Urology 63(4): 641-646.
Chang, C.I., Chan, D.C.D., Kuo, K.N., Hsiung,
C.A. & Chen, C.Y. 2010. Vitamin D insufficiency and frailty syndrome in
older adults living in a Northern Taiwan community. Archives of Gerontology
and Geriatrics 50: 17-21.
Cheng, X., Shen, Y. & Li, R. 2014. Targeting
TNF: A therapeutic strategy for Alzheimer’s disease. Drug Discovery Today 19(11):
1822-1827.
Chung, H.Y., Cesari, M., Anton, S., Marzetti,
E., Giovannini, S., Seo, A.Y. & Leeuwenburgh, C. 2009. Molecular
inflammation: Underpinnings of aging and age-related diseases. Ageing
Research Reviews 8(1): 18-30.
Collerton, J., Martin-Ruiz, C., Davies, K.,
Hilkens, C.M., Isaacs, J., Kolenda, C. & Jagger, C. 2012. Frailty and the
role of inflammation, immunosenescence and cellular ageing in the very old:
Cross-sectional findings from the Newcastle 85+ Study. Mechanisms of Ageing
and Development 133(6): 456-466.
Crentsil, V. 2010. Mechanistic contribution of
carnitine deficiency to geriatric frailty. Ageing Research Reviews 9(3):
265-268.
Dawson-Hughes, B., Heaney, R.P., Holick, M.F.,
Lips, P., Meunier, P.J. & Vieth, R. 2005. Estimates of optimal vitamin D
status. Osteoporosis International 16(7): 713-716.
de Gonzalo-Calvo, D., Neitzert, K., Fernández,
M., Vega-Naredo, I., Caballero, B., García-Macía, M. & Coto-Montes, A.
2010. Differential inflammatory responses in aging and disease: TNF-α and
IL-6 as possible biomarkers. Free Radical Biology and Medicine 49(5):
733-737.
Fernández-Garrido, J., Ruiz-Ros, V., Buigues,
C., Navarro- Martinez, R. & Cauli, O. 2014. Clinical features of prefrail
older individuals and emerging peripheral biomarkers: A systematic review. Archives
of Gerontology and Geriatrics 59(1): 7-17.
Ferrari, E. & Magri, F. 2008. Role of neuroendocrine
pathways in cognitive decline during aging. Ageing Research Reviews 7(3):
225-233.
Field, A. 2013. Discovering Statistics using
IBM SPSS Statistics. 4th ed. London: SAGE Publications Ltd.
Fried, L.P., Tangen, C.M., Walston, J., Newman,
A.B., Hirsch, C., Gottdiener, J. & Burke, G. 2001. Frailty in older adults
evidence for a phenotype. The Journals of Gerontology Series A: Biological
Sciences and Medical Sciences 56(3): M146-M157.
García-Esquinas, E., Navas-Acien, A.,
Pérez-Gómez, B. & Artalejo, F.R. 2015. Association of lead and cadmium
exposure with frailty in US older adults. Environmental Research 137:
424-431.
Hall, J.A. & Jewell, D.E. 2012. Feeding
healthy beagles medium-chain triglycerides, fish oil, and carnitine offsets
age-related changes in serum fatty acids and carnitine metabolites. PloS ONE 7(11): e49510.
Hubbard, R.E. & Woodhouse, K.W. 2010.
Frailty, inflammation and the elderly. Biogerontology 11(5): 635-641.
Jones, C. & Boelaert, K. 2014. The
endocrinology of ageing: A mini-review. Gerontology 61(4): 291-300.
Kumar, R., Mohan, N., Upadhyay, A.D., Singh,
A.P., Sahu, V., Dwivedi, S. & Dey, S. 2014. Identification of serum
sirtuins as novel noninvasive protein markers for frailty. Aging Cell 13(6):
975-980.
Lai, H.Y., Chang, H.T., Lee, Y.L. & Hwang,
S.J. 2014. Association between inflammatory markers and frailty in
institutionalized older men. Maturitas 79(3): 329-333.
Lang, P., Mitchell, W., Lapenna, A., Pitts, D.
& Aspinall, R. 2010. Immunological pathogenesis of main age-related
diseases and frailty: Role of immunosenescence. European Geriatric Medicine 1(2):
112-121.
Leng, S.X., Hung, W., Cappola, A.R., Yu, Q.,
Xue, Q.L. & Fried, L.P. 2009. White blood cell counts, insulin like growth
factor-1 levels, and frailty in community-dwelling older women. The Journals
of Gerontology Series A: Biological Sciences and Medical Sciences 64(4):
499-502.
Malaguarnera, M., Cammalleri, L., Gargante,
M.P., Vacante, M., Colonna, V. & Motta, M. 2007. L-Carnitine treatment
reduces severity of physical and mental fatigue and increases cognitive
functions in centenarians: A randomized and controlled clinical trial. The
American Journal of Clinical Nutrition 86(6): 1738-1744.
Marzetti, E., Calvani, R., Cesari, M., Buford, T.W., Lorenzi, M.,
Behnke, B.J. & Leeuwenburgh, C. 2013. Mitochondrial dysfunction and
sarcopenia of aging: From signaling pathways to clinical trials. The
International Journal of Biochemistry & Cell Biology 45(10): 2288-2301.
Mithal, A., Wahl, D.,
Bonjour, J.P., Burckhardt, P., Dawson- Hughes, B., Eisman, J. &
Morales-Torres, J. 2009. Global vitamin D status and determinants of
hypovitaminosis D. Osteoporosis International 20(11): 1807-1820.
Mocchegiani, E., Corsonello, A. & Lattanzio, F. 2010.
Frailty, ageing and inflammation: Reality and perspectives. Biogerontology 11(5):
523-525.
Mohamad, M.I. & Khater, M.S. 2015. Evaluation of insulin
like growth factor-1 (IGF-1) level and its impact on muscle and bone mineral
density in frail elderly male. Archives of Gerontology and Geriatrics 60(1):
124-127.
Pertosa, G., Grandaliano, G., Simone, S., Soccio, M. &
Schena, F.P. 2005. Inflammation and carnitine in hemodialysis patients. Journal
of Renal Nutrition 15(1): 8-12.
Prieto, J.A., Andrade, F., Aldámiz-Echevarría, L. &
Sanjurjo, P. 2006. Determination of free and total carnitine in plasma by an
enzymatic reaction and spectrophotometric quantitation spectrophotometric
determination of carnitine. Clinical Biochemistry 39(10): 1022-1027.
Puts, M.T., Visser, M., Twisk, J.W., Deeg, D.J. & Lips,
P. 2005. Endocrine and inflammatory markers as predictors of frailty. Clinical
Endocrinology 63(4): 403-411.
Rivero, J.L., Sporleder, H.P., Quiroz-Rothe, E., Vervuert,
I., Coenen, M. & Harmeyer, J. 2002. Oral L-carnitine combined with training
promotes changes in skeletal muscle. Equine Veterinary Journal 34:
269-274.
Rockwood, K., Andrew, M. & Mitnitski, A. 2007. A
comparison of two approaches to measuring frailty in elderly people. The
Journals of Gerontology Series A: Biological Sciences and Medical Sciences 62(7):
738-743.
Saum, K.U., Dieffenbach, A.K., Müezzinler, A., Müller, H.,
Holleczek, B., Stegmaier, C. & Stammer, H. 2014. Frailty and telomere
length: Cross-sectional analysis in 3537 older adults from the ESTHER cohort. Experimental
Gerontology 58: 250-255.
Schalk, B.W., Visser, M., Deeg, D.J. & Bouter, L.M.
2004. Lower levels of serum albumin and total cholesterol and future decline in
functional performance in older persons: The Longitudinal Aging Study
Amsterdam. Age and Ageing 33(3): 266-272.
Shahar, S., Omar, A., Vanoh, D., Hamid, T.A., Mukari,
S.Z.M.S., Din, N.C. & Loo, W.H. 2015. Approaches in methodology for
population-based longitudinal study on neuroprotective model for healthy longevity
(TUA) among Malaysian older adults. Aging Clinical and Experimental Research 28(6): 1089-1104.
Shamsi, K.S., Pierce, A., Ashton, A.S., Halade, D.G.,
Richardson, A. & Espinoza, S.E. 2012. Proteomic screening of glycoproteins
in human plasma for frailty biomarkers. The Journals of Gerontology Series
A: Biological Sciences and Medical Sciences 67(8): 853-864.
Villareal, D.T., Banks, M., Siener, C., Sinacore, D.R. &
Klein, S. 2004. Physical frailty and body composition in obese elderly men and
women. Obesity Research 12(6): 913-920.
Vogt, S., Decke, S., de las Heras Gala, T., Linkohr, B., Koenig,
W., Ladwig, K.H., Peters, A. & Thorand, B. 2015. Prospective
association of vitamin D with frailty status and all-cause mortality
in older adults-Results from the KORA-Age Study. Preventive
Medicine 73: 40-46.
Walston, J., Arking, D., Fallin, D., Li, T., Beamer, B.,
Xue, Q. & Chakravarti, A. 2005. IL-6 gene variation is not associated with
increased serum levels of IL-6, muscle, weakness, or frailty in older women. Experimental
Gerontology 40(4): 344-352.
Weiss, C.O. 2011. Frailty and chronic diseases in older
adults. Clinics in Geriatric Medicine 27(1): 39-52.
Wicherts, I.S., van Schoor, N.M., Boeke, A.J.P., Visser, M.,
Deeg, D.J., Smit, J. & Lips, P. 2007. Vitamin D status predicts physical
performance and its decline in older persons. The Journal of Clinical
Endocrinology & Metabolism 92(6): 2058-2065.
*Pengarang
untuk surat-menyurat; email: suzana.shahar@ukm.edu.my