Abstract
Aging diminishes hormone secretion and target cell responsiveness, possibly due to
loss of cell membrane fluidity or alteration of membrane phospholipids affecting signal
transduction. We investigated whether a high ω-3 polyunsaturated fatty acid diet would
improve endocrine function in 6 men and 6 women aged over 60 years. Subjects first
ate an isocaloric control diet for 6 weeks, followed by an 8-week experimental diet,
which included 720 g of fatty fish weekly plus 15 ml of sardine oil daily. In the
last week, we measured RBC membrane fatty acids on each diet, performed pituitary,
adrenal, hepatic, and Leydig cell endocrine provocative testing, and assayed selected
cytokines. We also assessed insulin sensitivity utilizing octreotide insulin suppression
testing and assessed free fatty acid (FFA) responses to isoproteronol. Insulin sensitivity
increased significantly after 8 weeks on the ω-3 diet and FFA responses trended lower.
Serum C-reactive protein was significantly reduced and a trend towards lower IL-6
was noted. No differences were found in other metabolic parameters, adiponectin levels,
or hormone responses. We conclude that, in older people, high ω-3 consumption increases
insulin sensitivity, may reduce FFA mobilization by catecholamines, and reduces inflammatory
markers, but did not alter endocrine responsiveness after 8 weeks.
Key words
omega-3 - diet - insulin - CRP - IL6 - hormones
References
- 1
Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR.
Longitudinal effects of aging on serum total and free testosterone levels in healthy
men. Baltimore Longitudinal Study of Aging.
J Clin Endocrinol Metab.
2001;
86
724-731
- 2
Tenover JS, Matsumoto AM, Plymate SR, Bremner WJ.
The effects of aging in normal men on bioavailable testosterone and luteinizing hormone
secretion: response to clomiphene citrate.
J Clin Endocrinol Metab.
1987;
65
1118-1126
- 3
Morley JE, Kaiser FE, Perry 3rd HM, Patrick P, Morley PM, Stauber PM. et al .
Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating
hormone in healthy older men.
Metabolism.
1997;
46
410-413
- 4
Harman SM, Tsitouras PD, Costa PT, Blackman MR.
Reproductive hormones in aging men. II. Basal pituitary gonadotropins and gonadotropin
responses to luteinizing hormone-releasing hormone.
J Clin Endocrinol Metab.
1982;
54
547-551
- 5
Nankin HR, Lin T, Murono ER, Osterman J.
The aging Leydig cell. III. Gonadotropin stimulation in men.
J Androl.
1981;
2
181-189
- 6
Sonntag WE, Gough MA.
Growth hormone releasing hormone induced release of growth hormone in aging male rats:
dependence on pharmacological manipulation and endogenous somatostatin release.
Neuroendocrinology.
1988;
47
482-488
- 7
Vittone J, Blackman MR, Busby-Whitehead J, Tsiao C, Stewart KJ, Tobin J. et al .
Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29)
in healthy elderly men.
Metabolism.
1997;
46
89-96
- 8
Corpas E, Harman SM, Blackman MR.
Human growth hormone and human aging.
Endocr Rev.
1993;
14
20-39
- 9
Kelijman M.
Age-related alterations of the growth hormone/insulin-like-growth-factor I axis.
J Am Geriatr Soc.
1991;
39
295-307
- 10 O’Connor KO, Stevens TE, Blackman MR. GH and Aging. In: Juul A, Jorgensen JOL (eds).
Growth Hormone in Adults. Cambridge: Cambridge University Press 1996: 323-366
- 11
Pavlov EP, Harman SM, Merriam GR, Gelato MC, Blackman MR.
Responses of growth hormone (GH) and somatomedin-C to GH-releasing hormone in healthy
aging men.
J Clin Endocrinol Metab.
1986;
62
595-600
- 12
Shibasaki T, Shizume K, Nakahara M, Masuda A, Jibiki K, Demura H. et al .
Age-related changes in plasma growth hormone response to growth hormone-releasing
factor in man.
J Clin Endocrinol Metab.
1984;
58
212-214
- 13
Copeland KC, Colletti RB, Devlin JT, MacAuliffe TL.
The relationship between insulin-like growth factor-I, adiposity, and aging.
Metabolism.
1990;
39
584-587
- 14
Dudl RJ, Ensinck JW.
Insulin and glucagon relationship during aging in man.
Metabolism.
1977;
26
33-41
- 15
Fink RI, Kolterman OG, Griffin J, Olefsky JM.
Mechanisms of insulin resistance in aging.
J Clin Invest.
1983;
71
1523-1535
- 16
Defronzo RA.
Glucose intolerance and aging: evidence for tissue insensitivity to insulin.
Diabetes.
1979;
28
1095-1101
- 17
Dax EM, Partilla JS, Pineyro MA, Gregerman RI.
Beta-adrenergic receptors, glucagon receptors, and their relationship to adenylate
cyclase in rat liver during aging.
Endocrinology.
1987;
120
1534-1541
- 18
Ishikawa Y, Gee MV, Baum BJ, Roth GS.
Decreased signal transduction in rat parotid cell aggregates during aging is not due
to loss of alpha 1-adrenergic receptors.
Exp Gerontol.
1989;
24
25-36
- 19
Roth GS.
Age changes in signal transduction and gene expression.
Mech Ageing Dev.
1997;
98
231-238
- 20
Roy D, Kalyanaraman B, Liehr JG.
Xanthine oxidase-catalyzed reduction of estrogen quinones to semiquinones and hydroquinones.
Biochem Pharmacol.
1991;
42
1627-1631
- 21
Gregerman RI.
Mechanisms of age-related alterations of hormone secretion and action. An overview
of 30 years of progress.
Exp Gerontol.
1986;
21
345-365
- 22
Awad AB.
Effect of dietary lipids on composition and glucose utilization by rat adipose tissue.
J Nutr.
1981;
111
34-39
- 23
Panek RL, Dixon WR, Rutledge CO.
Modification of sympathetic neuronal function in the rat tail artery by dietary lipid
treatment.
J Pharmacol Exp Ther.
1985;
233
578-583
- 24
Storlien LH, Kriketos AD, Jenkins AB, Baur LA, Pan DA, Tapsell LC. et al .
Does dietary fat influence insulin action?.
Ann N Y Acad Sci.
1997;
827
287-301
- 25
Feskens EJ, Bowles CH, Kromhout D.
Inverse association between fish intake and risk of glucose intolerance in normoglycemic
elderly men and women.
Diabetes Care.
1991;
14
935-941
- 26
Kowatch MA, Kelly JF, Denisova NA, Roth GS.
Partial restoration of impaired alpha 1-adrenergic responsiveness in parotid cells
of aged rats by S-adenosylmethionine treatment.
Mol Cell Biochem.
1995;
148
73-77
- 27
MacMurchie EJ, Margetts BM, Beilin LJ, Croft KD, Vandongen R, Armstrong BK.
Dietary-induced changes in the fatty acid composition of human cheek cell phospholipids:
correlation with changes in the dietary polyunsaturated/saturated fat ratio.
Am J Clin Nutr.
1984;
39
975-980
- 28
Stangl GI, Kirchgessner M, Eder K, Reichlmayr-Lais AM.
Effect of dietary hyperlipidemic components and fish oil on concentration of lipids
in liver and liver fatty acid profile of rats.
Z Ernahrungswiss.
1994;
33
195-206
- 29
Awad TB, Chattopadhyay JP.
Effect of dietary fats on the lipid composition and enzyme activities of rat cardiac
sarcolemma.
J Nutr.
1983;
113
1878-1883
- 30
Block G, Hartman AM, Dresser CM, Carroll MD, Gannon J, Gardner L.
A data-based approach to diet questionnaire design and testing.
Am J Epidemiol.
1986;
124
453-469
- 31
Block G, Coyle LM, Hartman AM, Scoppa SM.
Revision of dietary analysis software for the Health Habits and History Questionnaire.
Am J Epidemiol.
1994;
139
1190-1196
- 32
Daidoh H, Morita H, Mune T, Murayama M, Hanafusa J, Ni H. et al .
Responses of plasma adrenocortical steroids to low dose ACTH in normal subjects.
Clin Endocrinol (Oxf).
1995;
43
311-315
- 33
Crockford PM, Hazzard WR, Williams RH.
Insulin response to glucagons. The opposing effects of diabetes and obesity.
Diabetes.
1969;
18
216-224
- 34
Hoff AO, Vassilopoulou-Sellin R.
The role of glucagon administration in the diagnosis and treatment of patients with
tumor hypoglycemia.
Cancer.
1998;
82
1585-1592
- 35
Orme SM, Price A, Weetman AP, Ross RJ.
Comparison of the diagnostic utility of the simplified and standard I. m. glucagon
stimulation test (IMGST).
Clin Endocrinol (Oxf).
1998;
49
773-778
- 36
Harman SM, Tsitouras PD.
Reproductive hormones in aging men. I. Measurement of sex steroids, basal luteinizing
hormone, and Leydig cell response to human chorionic gonadotropin.
J Clin Endocrinol Metab.
1980;
51
35-40
- 37
Padron RS, Wischusen J, Hudson B, Burger HG, Kretser DM de.
Prolonged biphasic response of plasma testosterone to single intramuscular injections
of human chorionic gonadotropin.
J Clin Endocrinol Metab.
1980;
50
1100-1104
- 38
Tzvetkova P, Tzvetkov D, Kanchev L, Yanev V.
hCG stimulation test for diagnosis of androgen deficiency.
Arch Androl.
1997;
39
163-171
- 39
Tataranni PA, Christin L, Snitker S, Paolisso G, Ravussin E.
Pima Indian males have lower beta-adrenergic sensitivity than Caucasian males.
J Clin Endocrinol Metab.
1998;
83
1260-1263
- 40
Pei D, Jones CN, Bhargava R, Chen YD, Reaven GM.
Evaluation of octreotide to assess insulin-mediated glucose disposal by the insulin
suppression test.
Diabetologia.
1994;
37
843-845
- 41
Ohta A, Mayo MC, Kramer N, Lands WE.
Rapid analysis of fatty acids in plasma lipids.
Lipids.
1990;
25
742-747
- 42
Awad AB, Clay SW.
Age-dependent alterations in lipids and function of rat heart sarcolemma.
Mech Ageing Dev.
1982;
19
333-342
- 43
Yanagawa K, Takeda H, Egashira T, Sakai K, Takasaki M, Matsumiya T.
Age-related changes in alpha-tocopherol dynamics with relation to lipid hydroperoxide
content and fluidity of rat erythrocyte membrane.
J Gerontol A Biol Sci Med Sci.
1999;
54
379-383
- 44
Ando K, Beppu M, Kikugawa K.
Evidence for accumulation of lipid hydroperoxides during the aging of human red blood
cells in the circulation.
Biol Pharm Bull.
1995;
18
659-663
- 45
Hashimoto M, Hossain S, Masumura S.
Effect of aging on plasma membrane fluidity of rat aortic endothelial cells.
Exp Gerontol.
1999;
34
687-698
- 46
Hossain MS, Hashimoto M, Gamoh S, Masumura S.
Association of age-related decrease in platelet membrane fluidity with platelet lipid
peroxide.
Life Sci.
1999;
64
135-143
- 47
Mills DE, Galey WR, Dixon H.
Effects of dietary fatty-acid supplementation on fatty-acid composition and deformability
of young and old erythrocytes.
Biochim Biophys Acta.
1993;
1149
313-318
- 48
Dax EM, Partilla JS, Pineyro MA, Gregerman RI.
Altered glucagon- and catecholamine hormone-sensitive adenylyl cyclase responsiveness
in rat liver membranes induced by manipulation of dietary fatty acid intake.
Endocrinology.
1990;
127
2236-2240
- 49
Stefan N, Wahl HG, Fritsche A, Haring H, Stumvoll M.
Effect of the pattern of elevated free fatty acids on insulin sensitivity and insulin
secretion in healthy humans.
Horm Metab Res.
2001;
33
432-438
- 50
Clore JN, Stillman JS, Li J, O’Keefe SJ, Levy JR.
Differential effect of saturated and polyunsaturated fatty acids on hepatic glucose
metabolism in humans.
Am J Physiol Endocrinol Metab.
2004;
287
E358-E365
- 51
Neschen S, Moore I, Regittnig W, Yu CL, Wang Y, Pypaert M. et al .
Contrasting effects of fish oil and safflower oil on hepatic peroxisomal and tissue
lipid content.
Am J Physiol Endocrinol Metab.
2002;
282
E395-E401
- 52
Jucker BM, Cline GW, Barucci N, Shulman GI.
Differential effects of safflower oil versus fish oil feeding on insulin-stimulated
glycogen synthesis, glycolysis, and pyruvate dehydrogenase flux in skeletal muscle:
a 13C nuclear magnetic resonance study.
Diabetes.
1999;
48
134-140
- 53
Giron MD, Salto R, Hortelano P, Periago JL, Vargas AM, Suarez MD.
Increased diaphragm expression of GLUT4 in control and streptozotocin-diabetic rats
by fish oil-supplemented diets.
Lipids.
1999;
34
801-807
- 54
Sohal PS, Baracos VE, Clandinin MT.
Dietary omega 3 fatty acid alters prostaglandin synthesis, glucose transport and protein
turnover in skeletal muscle of healthy and diabetic rats.
Biochem J.
1992;
286
((Pt 2))
405-411
- 55
MacManus RM, Jumpson J, Finegood DT, Clandinin MT, Ryan EA.
A comparison of the effects of n-3 fatty acids from linseed oil and fish oil in well-controlled
type II diabetes.
Diabetes Care.
1996;
19
463-467
- 56
Annuzzi G, Rivellese A, Capaldo B, Di Marino L, Iovine C, Marotta G. et al .
A controlled study on the effects of n-3 fatty acids on lipid and glucose metabolism
in non-insulin-dependent diabetic patients.
Atherosclerosis.
1991;
87
65-73
- 57
Boberg M, Pollare T, Siegbahn A, Vessby B.
Supplementation with n-3 fatty acids reduces triglycerides but increases PAI-1 in
non-insulin-dependent diabetes mellitus.
Eur J Clin Invest.
1992;
22
645-650
- 58
Rivellese AA, Maffettone A, Iovine C, Di Marino L, Annuzzi G, Mancini M. et al .
Long-term effects of fish oil on insulin resistance and plasma lipoproteins in NIDDM
patients with hypertriglyceridemia.
Diabetes Care.
1996;
19
1207-1213
- 59
Luo J, Rizkalla SW, Vidal H, Oppert JM, Colas C, Boussairi A. et al .
Moderate intake of n-3 fatty acids for 2 months has no detrimental effect on glucose
metabolism and could ameliorate the lipid profile in type 2 diabetic men. Results
of a controlled study.
Diabetes Care.
1998;
21
717-724
- 60
Geusens P, Wouters C, Nijs J, Jiang Y, Dequeker J.
Long-term effect of omega-3 fatty acid supplementation in active rheumatoid arthritis.
A 12-month, double-blind, controlled study.
Arthritis Rheum.
1994;
37
824-829
- 61
Kremer JM, Lawrence DA, Petrillo GF, Litts LL, Mullaly PM, Rynes RI. et al .
Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal
antiinflammatory drugs. Clinical and immune correlates.
Arthritis Rheum.
1995;
38
1107-1114
- 62
Endres S, Lorenz R, Loeschke K.
Lipid treatment of inflammatory bowel disease.
Curr Opin Clin Nutr Metab Care.
1999;
2
117-120
- 63
Trichopoulou A, Bamia C, Trichopoulos D.
Mediterranean diet and survival among patients with coronary heart disease in Greece.
Arch Intern Med.
2005;
165
929-935
- 64
Trichopoulou A, Orfanos P, Norat T, Bueno-de-Mesquita B, Ocke MC, Peeters PH. et al
.
Modified Mediterranean diet and survival: EPIC-elderly prospective cohort study.
BMJ.
2005;
330
991
- 65
Knoops KT, Groot LC de, Kromhout D, Perrin AE, Moreiras-Varela O, Menotti A. et al
.
Mediterranean diet, lifestyle factors, and 10-year mortality in elderly European men
and women: the HALE project.
JAMA.
2004;
292
1433-1439
Correspondence
P. D. TsitourasMD
Kronos Longevity Research Institute
2390 E. Camelback Road - Suite 440
Phoenix
85016 AZ
USA
Telefon: +1/602/778 74 93
Fax: +1/602/778 74 90
eMail: tsitouras@kronosinstitute.org