• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
  LongeCity
              Advocacy & Research for Unlimited Lifespans

Photo
- - - - -

How best to raise LDL-C and TC

ldl hdl cholesterol stroke hemorrhagic stroke intracerebral hemorrhage

  • Please log in to reply
9 replies to this topic

#1 Zerry

  • Guest
  • 7 posts
  • 2
  • Location:Chicago
  • NO

Posted 27 June 2015 - 08:44 PM


I have a family history of hemorrhagic stroke. No history of ischemic stroke, and very few heart attacks. Additionally, I think I personally have a low risk of heart attack from my lifestyle. That leaves a high risk of hemorrhagic stroke.

 
I have been looking at ways to lower my risk. The risk factors for hemorrhagic stroke (intracerebral hemorrhage) are often the exact opposite compared to ischemic stroke or heart attack. See references below.
 
Higher risk of hemorrhagic stroke:
  • LOW Total Cholesterol
  • LOW LDL
  • HIGH HDL
  • LOW Triglycerides
  • LOW Protein diet
  • LOW Saturated fat
Lower risk of hemorrhagic stroke:
  • Egg consumption
  • Animal protein
What's the best, safest, healthiest way to raise my LDL-C and Total Cholesterol?
I started eating more eggs and animal protein. Is there anything else I should do?
 
Thanks.
 
 
 
 
References: (There are some conflicting studies too.)
 
 
Stroke. 2013 Jul;44(7):1833-9.
Cholesterol levels and risk of hemorrhagic stroke: a systematic review and meta-analysis.
Wang X1, Dong Y, Qi X, Huang C, Hou L.
"Total cholesterol level is inversely associated with risk of hemorrhagic stroke. Higher level of low-density lipoprotein cholesterol seems to be associated with lower risk of hemorrhagic stroke. High-density lipoprotein cholesterol level seems to be positively associated with risk of intracerebral hemorrhage."
PMID: 23704101
 
Stroke. 2013 May;44(5):1354-9. 
Lipid profile, lipid-lowering medications, and intracerebral hemorrhage after tPA in get with the guidelines-stroke.
Messé SR1, Pervez MA, Smith EE, Siddique KA, Hellkamp AS, Saver JL, Bhatt DL, Fonarow GC, Peterson ED, Schwamm LH.
"...higher high density lipoprotein and lower triglyceride levels were modest risk factors."
PMID: 23493734
 
BMJ. 2013 Jan 7;346:e8539.
Egg consumption and risk of coronary heart disease and stroke: dose-response meta-analysis of prospective cohort studies.
Rong Y1, Chen L, Zhu T, Song Y, Yu M, Shan Z, Sands A, Hu FB, Liu L.
"...reduced risk of hemorrhagic stroke associated with higher egg consumption in subgroup analyses warrant further studies."
PMID: 23295181
 
Ann Indian Acad Neurol. 2012 Jan;15(1):19-22.
Low cholesterol as a risk factor for primary intracerebral hemorrhage: A case-control study.
Valappil AV1, Chaudhary NV, Praveenkumar R, Gopalakrishnan B, Girija AS.
"This study confirms an increased risk of primary [intracerebral hemorrhage] associated with low cholesterol both in men and women, especially in older individuals."
PMID: 22412267
 
Arterioscler Thromb Vasc Biol. 2011 Dec;31(12):2982-9.
Serum lipid levels and the risk of intracerebral hemorrhage: the Rotterdam Study.
Wieberdink RG1, Poels MM, Vernooij MW, Koudstaal PJ, Hofman A, van der Lugt A, Breteler MM, Ikram MA.
"Low serum triglyceride levels were associated with an increased risk of intracerebral hemorrhage and with the presence of deep or infratentorial cerebral microbleeds."
PMID: 21921260
 
Stroke. 2011 Sep;42(9):2447-52. 
Serum low-density lipoprotein cholesterol level predicts hematoma growth and clinical outcome after acute intracerebral hemorrhage.
Rodriguez-Luna D1, Rubiera M, Ribo M, Coscojuela P, Pagola J, Piñeiro S, Ibarra B, Meler P, Maisterra O, Romero F, Alvarez-Sabin J, Molina CA.
"Lower serum LDL-C level independently predicts [hematoma growth], early neurological deterioration, and 3-month mortality after acute [intracerebral hemorrhage]."
PMID: 21799167 
 
EPMA J. 2011 Mar;2(1):75-81. 
Associations of impaired glucose metabolism and dyslipidemia with cardiovascular diseases: what have we learned from Japanese cohort studies for individualized prevention and treatment?
Kokubo Y1.
"...lower LDL-C levels may pose an increased risk of intracerebral hemorrhage"
PMID: 231991
 
Cerebrovasc Dis. 2011;31(1):100-6.
Blood pressure and total cholesterol level are critical risks especially for hemorrhagic stroke in Akita, Japan.
Suzuki K1, Izumi M, Sakamoto T, Hayashi M.
"High BP and low [total cholesterol] (<160 mg/dl) were critical risks of hemorrhagic stroke."
PMID: 21079399
 
Zhonghua Xin Xue Guan Bing Za Zhi. 2010 Mar;38(3):268-71.
[Prospective study on associations between levels of total cholesterol, triglyceride and risk of ischemic and hemorrhagic strokes].
Jiang B1, Fang XH, Liu YH, Dai XY, Lin ZG, Su FZ, Yang QD, Wang WZ, Wu SP, Li SC.
"low TC was related with increased risk of hemorrhagic stroke."
PMID: 20450572
 
Atherosclerosis. 2010 May;210(1):243-8. 
Triglycerides and risk of hemorrhagic stroke vs. ischemic vascular events: The Three-City Study.
Bonaventure A1, Kurth T, Pico F, Barberger-Gateau P, Ritchie K, Stapf C, Tzourio C.
"...low triglycerides levels were associated with an increased risk of hemorrhagic stroke..."
PMID: 19963214
 
Acta Neurol Scand. 2009 Mar;119(3):151-4.
Association of low cholesterol with primary intracerebral haemorrhage: a case control study.
Orken DN1, Kenangil G, Celik M, Mail Z, Kayaalp H, Erginoz E, Forta H.
"Individuals with lower cholesterol levels have an increased risk of [intracerebral hemorrhage]. Therefore, before treatment with statins, clinicians must be aware of the possible [intracerebral hemorrhage] risk."
PMID: 18684213
 
MEDICC Rev. 2008 Apr;10(2):27-32.
Association between Blood Lipids and Types of Stroke.
González S1, Fernández O, Fernández R, Menéndez C, Maza J, González-Quevedo A, Buergo MA.
"...low total cholesterol levels and high triglycerides levels are associated with the [cerebral hemorrhage] occurrence."
PMID: 21483365
 
Am J Epidemiol. 2003 Jan 1;157(1):32-9.
Fat and protein intakes and risk of intraparenchymal hemorrhage among middle-aged Japanese.
Iso H1, Sato S, Kitamura A, Naito Y, Shimamoto T, Komachi Y.
"Intake of animal protein tended to correlate inversely with risk; the relative risk with a one standard deviation increase in animal protein intake (17.6 g/day) was 0.79 (95% CI: 0.61, 1.02); p = 0.07. Results are similar to those recently reported for US women and together help to explain the high rate of this stroke subtype in Asian countries, where intakes of these nutrients are low."
PMID: 12505888
 
Circulation. 2001 Feb 13;103(6):856-63.
Prospective study of fat and protein intake and risk of intraparenchymal hemorrhage in women.
Iso H1, Stampfer MJ, Manson JE, Rexrode K, Hu F, Hennekens CH, Colditz GA, Speizer FE, Willett WC.
"Low intake of saturated fat and animal protein was associated with an increased risk of intraparenchymal hemorrhage, which may help to explain the high rate of this stroke subtype in Asian countries. The increased risk with low intake of saturated fat and trans unsaturated fat is compatible with the reported association between low serum total cholesterol and risk."
PMID: 11171795

Edited by Zerry, 27 June 2015 - 08:52 PM.

  • Dangerous, Irresponsible x 2
  • Ill informed x 1
  • WellResearched x 1

#2 Matt

  • Guest
  • 2,862 posts
  • 149
  • Location:United Kingdom
  • NO

Posted 28 June 2015 - 01:35 PM

If you reduce inflammation, reduce glycation-induced cross-linking, and keep your blood pressure low, you'll be fine. There's no need to increase LDL and TC unless your blood pressure is high. So keep it under 115, pref around 100/60 and don't increase your LDL.


Edited by Matt, 28 June 2015 - 01:37 PM.

  • Agree x 1

sponsored ad

  • Advert
Click HERE to rent this advertising spot for NUTRITION to support LongeCity (this will replace the google ad above).

#3 Zerry

  • Topic Starter
  • Guest
  • 7 posts
  • 2
  • Location:Chicago
  • NO

Posted 29 June 2015 - 12:06 AM

I will do everything I can for my blood pressure, of course. There are other targets I'm looking at too.

 

Why do you say there's no need to increase LDL and TC unless my bp is high? What's the reasoning there?

 

Thanks.



#4 Dolph

  • Guest
  • 512 posts
  • 122
  • Location:Germany

Posted 29 June 2015 - 09:04 AM

The (strong) reasoning is that the VERY questionable reduction in hemorrhagic stroke you would get with an increase in LDL would be more than compensated for by a serveral fold INCREASE of the risk of atherotrombotic CVD. And we are talking about orders of magnitude here... 

As Matt already explained. The primary risk factor for stroke is blood pressure. Do everything to get this as low as possible and be happy that your LDL is so low without having to do anything about it.


  • like x 1
  • Agree x 1

#5 Zerry

  • Topic Starter
  • Guest
  • 7 posts
  • 2
  • Location:Chicago
  • NO

Posted 29 June 2015 - 08:05 PM

I never meant to imply that blood pressure was not important, or less important than cholesterol.



#6 pamojja

  • Guest
  • 2,837 posts
  • 720
  • Location:Austria

Posted 29 June 2015 - 08:22 PM

 

Lower risk of hemorrhagic stroke:
  • Egg consumption
  • Animal protein

 

After being a livelong low-fat vegetarian and the diagnosis of a severe peripheral artery disease (PAD) I started egg and fish consumption. My LDL and total Cholesterol only went down (about 42% in average the last 6 years). However, on my vacations each of the last 3 years in South-India with the higher carb diet there (rice, chapatis, lentils) both of them unfailingly rose for a short time again.

 

So maybe a high sugar diet? :cool:


  • Dangerous, Irresponsible x 1
  • Cheerful x 1

#7 Zerry

  • Topic Starter
  • Guest
  • 7 posts
  • 2
  • Location:Chicago
  • NO

Posted 29 June 2015 - 08:42 PM

Pamojja, I'm sorry someone voted you Dangerous, Irresponsible. I know you were joking about the high sugar diet. That's why I started this thread, because I don't want to eat sugar to raise my LDL. I don't want to increase glycation, intake of glycated proteins or oxidized fats.



#8 pamojja

  • Guest
  • 2,837 posts
  • 720
  • Location:Austria

Posted 29 June 2015 - 09:18 PM

Pamojja, I'm sorry someone voted you Dangerous, Irresponsible.

 

Actually that was the first time I felt sorry for not being able to down-vote myself as Dangerous and Irresponsible.  :-D  So thanks to the voter, and anyone who wants to do me a favor, please down-vote me repeatedly again for that.

 

I don't want to eat sugar to raise my LDL. I don't want to increase glycation, intake of glycated proteins or oxidized fats.

Personally I would consider something maybe less vicious like white rice, while monitoring HbA1c, and just try how far eggs and grass-fed meats/fish are affecting your cholesterol numbers.


  • Dangerous, Irresponsible x 4

#9 Zerry

  • Topic Starter
  • Guest
  • 7 posts
  • 2
  • Location:Chicago
  • NO

Posted 02 July 2015 - 03:29 PM

The idea of trying to raise cholesterol to lower the risk of hemorrhagic stroke is based on the idea that cholesterol is your body trying to protect your blood vessels. Some "experts" and researchers, have put forth the theory that LDL itself isn't bad, it's a red herring. It's your body responding to something else that is damaging your blood vessels, like glycated proteins, homocysteine, peroxided lipids, etc. There are studies that suggest cholesterol is protective. If that's true, then high cholesterol is a sign, a result of damage that has occurred, not a cause. I can't post links, but googling this topic you can pretty easily find references that back this up. But, it's obviously controversial. A counter argument is that statins appear to be beneficial. To that, some argue that the protection by statins is from something other than lowering cholesterol, but no one knows what that mechanism is. I think most longecity readers are familiar with this idea.

One analogy off the top of my head is that high WBC count can be caused by infection. If I had a low WBC count, I could give myself an infection, and that might raise my WBC, but that would be stupid. I would want some other, safe way to raise my WBC count.

Going with this theory, I'm wondering how one could get their body to increase cholesterol without causing damage?

My only idea is to increase intake of actual cholesterol, like from eggs, to provide what we might call "cholesterol precursors", or the raw materials for my body to make its own cholesterol.

Other ideas?
Thoughts?

Thanks.
  • Ill informed x 1

#10 Brett Black

  • Guest
  • 353 posts
  • 174
  • Location:Australia

Posted 07 July 2015 - 06:55 AM

It may not be the higher cholesterol levels from meat eating that is providing protection from hemorrhagic stroke, it could actually be higher levels of IGF-1 / GH (IGF-1 and GH are closely related and often treated as a pair.) Dietary protein, and (if I recall correctly) particularly the amino acids found more abundantly in animal protein, are known to elevate IGF-1 levels.

There's a significant amount of evidence that IGF-1 is generally protective for the cardiovascular and cerebrovascular systems. IGF-1 is suggested to reduce both the incidence of, as well as improve the functional outcome of, hemorrhagic stroke.

A major complicating issue in seeking to boost IGF-1 though, is that increased IGF-1 has also unfortunately been associated with increased all-cause mortality, and particularly cancer mortality, in both humans and animal models. In fact, reduced IGF-1 activity has been vigorously studied as one of the most prominent biomarkers associated with dietary and genetic interventions for anti-ageing in animal models (including caloric restriction, protein/amino restriction and gene knock-out mice.)

So, on the one hand, increased dietary protein and IGF-1 may help protect against hemorrhagic stroke(as well as having many other benefits for age-associated declines of the heart, vasculature, brain, muscles, bones etc), but could potentially be opposed by the increased risk of all-cause mortality and cancer. This is consistent with observations showing the transition in developing countries from low animal protein largely vegan diets to more Westernized higher animal protein diets, and the cocomittant reduced stroke rates but increased cancer rates.

Deciding what level of IGF-1 to aim for may be a question of weighing up the various risks factor involved, and may need to take into account each individual's particular risks.

Below I have listed some of the better papers on these issues that I have found. Quoting from the excellent review by Sonntag et al:
 

"Based on the literature, GH and IGF-1 have both beneficial and deleterious effects on specific pathologies that undoubtedly influence lifespan. Therefore, in many cases, the consequences of GH and IGF-1 deficiency are dependent on the species, background strain, and pathologies that the species or strain is susceptible. Those animals that are at risk for cancer, liver, or kidney disease will likely exhibit a shortened life span in response to elevated levels of GH and IGF-1, and we expect that those animals with reduced risk for these diseases will likely not exhibit increased life span in response to this intervention. Similarly, those species at risk for specific cardiovascular diseases (stroke, myocardial infarction, heart failure, vascular cognitive impairment) may benefit from elevated levels of these hormones. These effects are consistent with the classical actions of GH and IGF-1 being important anabolic agents that stimulate cell growth, proliferation, and tissue repair. Because cardiovascular diseases, metabolic diseases, and cancer are all important health issues in the elderly population, the effects of GH/IGF-1 pathway on human health span and life span are predictably complex....

...GH/IGF-1–deficient Lewis dwarf rats, in which intracerebral hemorrhage is an important cause of death, do not exhibit a longevity phenotype in response to GH/IGF-1 deficiency. Rather, treatment with GH during adolescence is vasculoprotective and increases life span."




From Ungvari et al:

"In humans, growth hormone deficiency (GHD) and low circulating levels of insulin-like growth factor 1 (IGF-1) significantly increase the risk for cerebrovascular disease. Genetic growth hormone (GH)/IGF-1 deficiency in Lewis dwarf rats significantly increases the incidence of late-life strokes, similar to the effects of GHD in elderly humans. Peripubertal treatment of Lewis dwarf rats with GH delays the occurrence of late-life stroke, which results in a significant extension of life span."



Sontagg et al, with some counterbalancing of the view that lowering IGF-1 might increase lifespan in humans like it can in animal models:

"Importantly, the studies in humans on circulating GH and IGF-1 deficiency do not agree with the data from rodent models. GH/IGF-1–deficient dwarf humans can, under some circumstances, live as long as their non-GH/IGF-1–deficient peers, but in the majority of cases, they do not exhibit the increased life span that would be expected based on the relevant literature on laboratory animals."



There may be another safer avenue to elevating IGF-1 than eating animal-derived protein. Some evidence suggests that protein intake from plant sources does not pose the same potential risk of cancer and mortality (and high cholesterol, if the animal protein contains saturated fat) as that derived from animal sources, as the Longo paper reports:
 

"Respondents aged 50-65 reporting high protein intake had a 75% increase in overall mortality and a 4-fold increase in cancer death risk during the following 18 years. These associations were either abolished or attenuated if the proteins were plant derived."


Furthermore, the Fontana paper involved subjects from the Calorie Restriction Society, and I know that at least some of them initially had relatively high levels of IGF-1 whilst consuming an almost exclusively plant-based high protein diet, which subsequently dropped when they lowered their protein intake. So it seems that plant-derived protein is probably capable of maintaining high IGF-1 in humans.

None of this however answers the question of what IGF-1 serum levels might offer the best protection against hemorrhagic stroke in humans, and how variable this may be between individuals...


 

Med Hypotheses. 2003 Sep;61(3):323-34.

IGF-I activity may be a key determinant of stroke risk--a cautionary lesson for
vegans.


McCarty MF(1).

Author information:
(1)Pantox Laboratories, San Diego, California 92109, USA.

IGF-I acts on vascular endothelium to activate nitric oxide synthase, thereby
promoting vascular health; there is reason to believe that this protection is
especially crucial to the cerebral vasculature, helping to ward off thrombotic
strokes. IGF-I may also promote the structural integrity of cerebral arteries,
thereby offering protection from hemorrhagic stroke. These considerations may
help to explain why tallness is associated with low stroke risk, whereas growth
hormone deficiency increases stroke risk--and why age-adjusted stroke mortality
has been exceptionally high in rural Asians eating quasi-vegan diets, but has
been declining steadily in Asia as diets have become progressively higher in
animal products. There is good reason to suspect that low-fat vegan diets tend to
down-regulate systemic IGF-I activity; this effect would be expected to increase
stroke risk in vegans. Furthermore, epidemiology suggests that low serum
cholesterol, and possibly also a low dietary intake of saturated fat--both
characteristic of those adopting low-fat vegan diets--may also increase stroke
risk. Vegans are thus well advised to adopt practical countermeasures to minimize
stroke risk--the most definitive of which may be salt restriction. A high
potassium intake, aerobic exercise training, whole grains, moderate alcohol
consumption, low-dose aspirin, statin or policosanol therapy, green tea, and
supplementation with fish oil, taurine, arginine, and B vitamins--as well as
pharmacotherapy of hypertension if warranted--are other practical measures for
lowering stroke risk. Although low-fat vegan diets may markedly reduce risk for
coronary disease, diabetes, and many common types of cancer, an increased risk
for stroke may represent an 'Achilles heel'. Nonetheless, vegans have the
potential to achieve a truly exceptional 'healthspan' if they face this problem
forthrightly by restricting salt intake and taking other practical measures that
promote cerebrovascular health.

PMID: 12944100 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm....pubmed/12944100


1. J Gerontol A Biol Sci Med Sci. 2012 Jun;67(6):587-98. doi: 10.1093/gerona/gls115.
Epub 2012 Apr 20.

Diverse roles of growth hormone and insulin-like growth factor-1 in mammalian
aging: progress and controversies.


Sonntag WE(1), Csiszar A, deCabo R, Ferrucci L, Ungvari Z.

Author information:
(1)Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences
Center, Stanton L. Young Biomedical Research Center 1303, 975 NE 10th Street,
Oklahoma City, OK 74104, USA. william-sonntag@ouhsc.edu

Because the initial reports demonstrating that circulating growth hormone and
insulin-like growth factor-1 decrease with age in laboratory animals and humans,
there have been numerous studies related to the importance of these hormones for
healthy aging. Nevertheless, the role of these potent anabolic hormones in the
genesis of the aging phenotype remains controversial. In this chapter, we review
the studies demonstrating the beneficial and deleterious effects of growth
hormone and insulin-like growth factor-1 deficiency and explore their effects on
specific tissues and pathology as well as their potentially unique effects early
during development. Based on this review, we conclude that the perceived
contradictory roles of growth hormone and insulin-like growth factor-1 in the
genesis of the aging phenotype should not be interpreted as a controversy on
whether growth hormone or insulin-like growth factor-1 increases or decreases
life span but rather as an opportunity to explore the complex roles of these
hormones during specific stages of the life span.

PMCID: PMC3348498
PMID: 22522510 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm....pubmed/22522510


1. Cell Metab. 2014 Mar 4;19(3):407-17. doi: 10.1016/j.cmet.2014.02.006.

Low protein intake is associated with a major reduction in IGF-1, cancer, and
overall mortality in the 65 and younger but not older population.


Levine ME(1), Suarez JA(2), Brandhorst S(2), Balasubramanian P(2), Cheng CW(2),
Madia F(3), Fontana L(4), Mirisola MG(5), Guevara-Aguirre J(6), Wan J(2),
Passarino G(7), Kennedy BK(8), Wei M(2), Cohen P(2), Crimmins EM(1), Longo VD(9).

Author information:
(1)Davis School of Gerontology, University of Southern California, Los Angeles,
CA 90033, USA. (2)Davis School of Gerontology, University of Southern California,
Los Angeles, CA 90033, USA; Longevity Institute, University of Southern
California, Los Angeles, CA 90033, USA. (3)Davis School of Gerontology,
University of Southern California, Los Angeles, CA 90033, USA; EURL ECVAM,
Institute for Health & Consumer Protection, European Commission Joint Research
Centre, Ispra (VA) 21027, Italy. (4)Department of Medicine, Washington University
in St. Louis, St. Louis, MO 63110, USA; Department of Clinical and Experimental
Sciences, Brescia University School of Medicine, Brescia 25123, Italy; CEINGE
Biotecnologie Avanzate, Napoli 80145, Italy. (5)Davis School of Gerontology,
University of Southern California, Los Angeles, CA 90033, USA; Longevity
Institute, University of Southern California, Los Angeles, CA 90033, USA;
Dipartimento di Biopatologia e Metodologie Biomediche, Universita' di Palermo,
Palermo 90127, Italy. (6)Universidad San Francisco de Quito & Instituto IEMYR,
Quito 17-1200-841, Ecuador. (7)Department of Biology, Ecology and Earth Science,
University of Calabria, Rende 87036, Italy. (8)Buck Institute for Research on
Aging, Novato, CA 94945, USA. (9)Davis School of Gerontology, University of
Southern California, Los Angeles, CA 90033, USA; Longevity Institute, University
of Southern California, Los Angeles, CA 90033, USA. Electronic address:
vlongo@usc.edu.

Comment in
Science. 2014 Mar 7;343(6175):1068.

Mice and humans with growth hormone receptor/IGF-1 deficiencies display major
reductions in age-related diseases. Because protein restriction reduces GHR-IGF-1
activity, we examined links between protein intake and mortality. Respondents
aged 50-65 reporting high protein intake had a 75% increase in overall mortality
and a 4-fold increase in cancer death risk during the following 18 years. These
associations were either abolished or attenuated if the proteins were plant
derived. Conversely, high protein intake was associated with reduced cancer and
overall mortality in respondents over 65, but a 5-fold increase in diabetes
mortality across all ages. Mouse studies confirmed the effect of high protein
intake and GHR-IGF-1 signaling on the incidence and progression of breast and
melanoma tumors, but also the detrimental effects of a low protein diet in the
very old. These results suggest that low protein intake during middle age
followed by moderate to high protein consumption in old adults may optimize
healthspan and longevity.

Copyright © 2014 Elsevier Inc. All rights reserved.

PMCID: PMC3988204
PMID: 24606898 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm....pubmed/24606898


1. J Gerontol A Biol Sci Med Sci. 2010 Nov;65(11):1145-56. doi:
10.1093/gerona/glq147. Epub 2010 Aug 16.

Vasoprotective effects of life span-extending peripubertal GH replacement in
Lewis dwarf rats.


Ungvari Z(1), Gautam T, Koncz P, Henthorn JC, Pinto JT, Ballabh P, Yan H,
Mitschelen M, Farley J, Sonntag WE, Csiszar A.

Author information:
(1)Reynolds Oklahoma Center on Aging, Donald W. Reynolds Department of Geriatric
Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104,
USA.

In humans, growth hormone deficiency (GHD) and low circulating levels of
insulin-like growth factor 1 (IGF-1) significantly increase the risk for
cerebrovascular disease. Genetic growth hormone (GH)/IGF-1 deficiency in Lewis
dwarf rats significantly increases the incidence of late-life strokes, similar to
the effects of GHD in elderly humans. Peripubertal treatment of Lewis dwarf rats
with GH delays the occurrence of late-life stroke, which results in a significant
extension of life span. The present study was designed to characterize the
vascular effects of life span-extending peripubertal GH replacement in Lewis
dwarf rats. Here, we report, based on measurements of dihydroethidium
fluorescence, tissue isoprostane, GSH, and ascorbate content, that peripubertal
GH/IGF-1 deficiency in Lewis dwarf rats increases vascular oxidative stress,
which is prevented by GH replacement. Peripubertal GHD did not alter superoxide
dismutase or catalase activities in the aorta nor the expression of Cu-Zn-SOD,
Mn-SOD, and catalase in the cerebral arteries of dwarf rats. In contrast,
cerebrovascular expression of glutathione peroxidase 1 was significantly
decreased in dwarf vessels, and this effect was reversed by GH treatment.
Peripubertal GHD significantly decreases expression of the Nrf2 target genes NQO1
and GCLC in the cerebral arteries, whereas it does not affect expression and
activity of endothelial nitric oxide synthase and vascular expression of IGF-1,
IGF-binding proteins, and inflammatory markers (tumor necrosis factor alpha,
interluekin-6, interluekin-1ß, inducible nitric oxide synthase, intercellular
adhesion molecule 1, and monocyte chemotactic protein-1). In conclusion,
peripubertal GH/IGF-1 deficiency confers pro-oxidative cellular effects, which
likely promote an adverse functional and structural phenotype in the vasculature,
and results in accelerated vascular impairments later in life.

PMCID: PMC2954243
PMID: 20713653 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm....pubmed/20713653


1. Aging Cell. 2008 Oct;7(5):681-7.

Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3
concentration in humans.


Fontana L(1), Weiss EP, Villareal DT, Klein S, Holloszy JO.

Author information:
(1)Division of Geriatrics & Nutritional Sciences, Washington University School of
Medicine, St Louis, MO 63110, USA. lfontana@dom.wustl.edu

Comment in
Aging Cell. 2009 Apr;8(2):214; author reply 215.

Reduced function mutations in the insulin/IGF-I signaling pathway increase
maximal lifespan and health span in many species. Calorie restriction (CR)
decreases serum IGF-1 concentration by ~40%, protects against cancer and slows
aging in rodents. However, the long-term effects of CR with adequate nutrition on
circulating IGF-1 levels in humans are unknown. Here we report data from two
long-term CR studies (1 and 6 years) showing that severe CR without malnutrition
did not change IGF-1 and IGF-1 : IGFBP-3 ratio levels in humans. In contrast,
total and free IGF-1 concentrations were significantly lower in moderately
protein-restricted individuals. Reducing protein intake from an average of 1.67 g
kg(-1) of body weight per day to 0.95 g kg(-1) of body weight per day for 3 weeks
in six volunteers practicing CR resulted in a reduction in serum IGF-1 from 194
ng mL(-1) to 152 ng mL(-1). These findings demonstrate that, unlike in rodents,
long-term severe CR does not reduce serum IGF-1 concentration and IGF-1 : IGFBP-3
ratio in humans. In addition, our data provide evidence that protein intake is a
key determinant of circulating IGF-1 levels in humans, and suggest that reduced
protein intake may become an important component of anticancer and anti-aging
dietary interventions.

PMCID: PMC2673798
PMID: 18843793 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm....pubmed/18843793


1. J Gerontol A Biol Sci Med Sci. 2012 Jun;67(6):626-39. doi: 10.1093/gerona/gls102.
Epub 2012 Apr 5.

Aging, atherosclerosis, and IGF-1.

Higashi Y(1), Sukhanov S, Anwar A, Shai SY, Delafontaine P.

Author information:
(1)Tulane University Heart & Vascular Institute, Tulane University School of
Medicine, New Orleans, Louisiana 70112, USA.

Insulin-like growth factor 1 (IGF-1) is an endocrine and autocrine/paracrine
growth factor that circulates at high levels in the plasma and is expressed in
most cell types. IGF-1 has major effects on development, cell growth and
differentiation, and tissue repair. Recent evidence indicates that IGF-1 reduces
atherosclerosis burden and improves features of atherosclerotic plaque stability
in animal models. Potential mechanisms for this atheroprotective effect include
IGF-1-induced reduction in oxidative stress, cell apoptosis, proinflammatory
signaling, and endothelial dysfunction. Aging is associated with increased
vascular oxidative stress and vascular disease, suggesting that IGF-1 may exert
salutary effects on vascular aging processes. In this review, we will provide a
comprehensive update on IGF-1's ability to modulate vascular oxidative stress and
to limit atherogenesis and the vascular complications of aging.

PMCID: PMC3348497
PMID: 22491965 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm....pubmed/22491965



You may also want to check out more work from Sonntag on IGF-1 and cerebrovascular health and disease:
http://www.ncbi.nlm.... WE[auth] igf-1

Edited by Brett Black, 07 July 2015 - 07:13 AM.

  • like x 2
  • WellResearched x 1





Also tagged with one or more of these keywords: ldl, hdl, cholesterol, stroke, hemorrhagic stroke, intracerebral hemorrhage

0 user(s) are reading this topic

0 members, 0 guests, 0 anonymous users