Wuzzy
Thu, Oct-24-02, 20:58
Bobo wrote:
> A recent article in Jama advised people w/o compelling risk
> factors to avoid a homocysteine test. I personally have a H
> level of about 9, and recently started taking TMG along
> with my B mix. I wonder if I should discontinue this
> regime......... "Homocysteine levels appear to be a less
> important risk factor from the most recent data," according
> to Dr. Peter W. F. Wilson of SOURCE: The Journal of the
> American Medical Association 2002;288:2015-2031, 2042-2043.
"Homocysteine and Risk of Ischemic Heart Disease and Stroke",a
metaanalysis"
I briefly read this article, and did not get the impression
that people should "avoid" the test - here is the conclusion:
"If the modest associations observed in this study are causal,
then the implications for public health of decreasing the
population mean levels of homocysteine could still be
substantial. "
-wuzzy offtopic: I'm reading an article on a related topic and
wrestling with these ideas.. There is some complexity in terms
of statistics and nutrition: nutrition has only a modest
effect on disease compared to natural population variation, so
it makes one wonder if individuals can be affected by diet,
certainly the populations risk of disease might affected
whereas individuals might be harder to predict.. okay will
wrestle more haven't finished the paper yet..
Thomas Car
Fri, Oct-25-02, 20:57
"michaelprice" <michaelprice@ntlworld.com> wrote in message
news:<LA6u9.70$GK4.29606@newsfep1-win.server.ntli.net>...
> wuzzy <mypcos@hotmail.com> wrote
> > Bobo wrote:
> >
> >> A recent article in Jama advised people w/o compelling
> >> risk factors to avoid a homocysteine test. I personally
> >> have a H level of about 9, and recently started taking
> >> TMG along with my B mix. I wonder if I should
> >> discontinue this regime......... "Homocysteine levels
> >> appear to be a less important risk factor from the most
> >> recent data," according to Dr. Peter W. F. Wilson of
> >> SOURCE: The Journal of the American Medical Association
> >> 2002;288:2015-2031, 2042-2043.
> > "Homocysteine and Risk of Ischemic Heart Disease and
> > Stroke",a metaanalysis"
>
> Do have the PMID? I couldn't locate this on PubMed.
>
> Cheers, Michael C Price
> ----------------------------------------
Hi Michael, Go to http://www.reutershealth.com/en/index.html
Then click on search and search for homocysteine. The article
is your first hit. It references two articles in JAMA, one is
not yet in PubMed the other
is:
CONCLUSIONS: Individuals with the MTHFR 677 TT genotype had a
significantly higher risk of CHD, particularly in the setting
of low folate status. These results support the hypothesis
that impaired folate metabolism, resulting in high
homocysteine levels, is causally related to increased risk of
CHD. PMID: 12387655
I agree with Wilson that homocysteiene is less important
in CVD than generally thought, but not because of the new
paper. (a mega analysis)It mearly describes the
relationship in a less sensational manner than previous
papers. It says an 11% decrease for those with levels 25%
less THAN AVERAGE. Many of the older studies used the
sensationalists method of reporting comaparisons between
extreme quintiles and got something like 30-40%
differences, usually not giving the breakdown between all
the quintiles in the abstracts. Thus much of the reported
benefit is due to avoiding malnutrition and little or none
is due to getting into the upper quintile from the
average. This is the goal of most people who supplement.
It can be quite difficult to avoid being subconsciously
influenced in one's attitudes by being constantly exposed
to propagandistic statistics. The take home message that
the brain remembers is the "30-40$" and the details seem
to get lost. In the case of homocysteine we can now see
that there seems to be a rather linear dose response
between quintiles. A paragraph from the article points out
quite well the contradictory paradigm under which the
"medical establishment" treats us: 'According to Wilson,
the author of the editorial, "taking vitamins, especially
multivitamins that contain folic acid, is not formally
recommended at this time to prevent cardiovascular
disease, but there is little harm and possibly some
benefit to taking them." He noted that vitamins often
lower homocysteine and are usually inexpensive.' When
people known to be smart can behave in such a manner so
apparently stupid there is always a reason behind their
madness. In this case it could have something to do with
insurance payments for homocysteine blood test and/or
paying for "prescribed" vitamins. Thomas
Michaelpri
Fri, Oct-25-02, 20:57
Hi Thomas,
thanks for the pointer. Its interesting that one of the
homocysteine studies related to the thermolabile form of a
folate coenzyme, MTHFR, (due to the MTHFR 677C->T genotype, a
dysfunction of folate metabolism, which 10-15% of us have),
which is correctable with extra riboflavin (B2), not
folate.[115] Coincidently, this was one of the updates I
recently made to my "living to 200" monograph.
I agree with Thomas that some (but not all) of the
homocysteine bandwagon is just hype. The benefit, though
tangible and real, with respect to CVD, is not as great as
some presentations imply. It's also important to point out
that *some* of the alleged benefits of low homocysteine *are*
completely illusory. For instance it is not of any benefit in
preventing Alzheimer's[79] - despite claims to the contrary
based on association - although taking co-enzymes/B-vitamins,
some of which also lower homocysteine, are of benefit for
Alzheimer's via other pathways and mechanisms. Intervention
trials with B1 (thiamine)[106a-c], B9 (folate)
[107], B12 (cobalamin)[104] , acetyl-L-carnitine[105]
(precursor to coenzyme carnitine) and alpha lipoic
acid[98] (precursor to coenzyme lipoamide) have all shown
success, to varying degrees, in stabilising the
progression (and presumably prevention also) of
Alzheimer's and other forms of dementia[106d].
[107a] Elevated plasma homocysteine levels in centenarians are
not associated with cognitive impairment. Ravaglia G,
Forti P, Maioli F, Vettori C, Grossi G, Bargossi AM,
Caldarera M, Franceschi C, Facchini A, Mariani E,
Cavalli G in Mech Ageing Dev 2000 Dec
20;121(1-3):251-61 "Demented centenarians had the
lowest folate serum levels."
[107b] Homocysteine, vitamin B6, and vascular disease in AD
patients. Miller JW, Green R, Mungas DM, Reed BR,
Jagust WJ in Neurology 2002 May 28;58(10):1471-5
"Elevated plasma homocysteine in patients with AD
appears related to vascular disease and not AD
pathology. In addition, low vitamin B(6) status is
prevalent in patients with AD."
[108] Alpha-lipoic acid as a new treatment option for Azheimer
type dementia. Hager K, Marahrens A, Kenklies M,
Riederer P, Munch G in Arch Gerontol Geriatr 2001
Jun;32(3):275-282 "600 mg alpha-lipoic acid was given
daily to nine patients with AD and related dementias [.]
The treatment led to a stabilization of cognitive
functions in the study group"
[108a] Treatment of Alzheimer-type dementia with intravenous
mecobalamin. Ikeda T, Yamamoto K, Takahashi K, Kaku Y,
Uchiyama M, Sugiyama K, Yamada M in Clin Ther 1992
May-Jun;14(3):426-37 "We conclude that mecobalamin is a
safe and effective treatment for
psychiatric disorders in patients with Alzheimer-type
dementia."
[108b] Vitamin B12 deficiency and dementia. Cunha UG, Rocha
FL, Peixoto JM, Motta MF, Barbosa MT in Int
Psychogeriatr 1995 Spring;7(1):85-8 "All of the
patients who showed some improvement (MMSE returned to
normal values) had mild dementia with a history of less
than 2 years. Thus, screening for B12 deficiency should
be considered in patients with recent onset of mild
mental status changes."
[108c] Treatment of cobalamin deficiency in dementia,
evaluated clinically and with cerebral blood flow
measurements. Nilsson K, Warkentin S, Hultberg B, Faldt
R, Gustafson L in Aging (Milano) 2000 Jun;12(3):199-207
"Fifteen patients who showed mild to moderate dementia
improved clinically, and also showed a concomitant
increase in their general CBF after treatment. In
contrast, 9 patients who were severely demented showed
no obvious clinical improvement, and no general blood
flow change, although some regional flow increases were
seen in sensory motor areas."
[108d] Effects of vitamin B12 on bright light on cognitive and
sleep-wake rhythm in Alzheimer-type dementia. Ito T,
Yamadera H, Ito R, Suzuki H, Asayama K, Endo S in ]
Psychiatry Clin Neurosci 2001 Jun;55(3):281-2 "These
results suggest that VB12 has some efficiency to
enhance vigilance for ATD patients."
[108e] The frequently low cobalamin levels in dementia usually
signify treatable metabolic, neurologic and
electrophysiologic abnormalities. Carmel R, Gott PS,
Waters CH, Cairo K, Green R, Bondareff W, DeGiorgio CM,
Cummings JL, Jacobsen DW, Buckwalter G, et al in Eur J
Haematol 1995 Apr;54(4):245-53 "Although the
long-standing dementia does not improve, treating such
patients with cobalamin has other concrete benefits."
[108f] Double-blind, placebo controlled study of
acetyl-l-carnitine in patients with Alzheimer's
dementia. Rai G, Wright G, Scott L, Beston B, Rest J,
Exton-Smith AN in Curr Med Res Opin 1990;11(10):638-47
"The results suggest that acetyl-l-carnitine may have a
beneficial effect on some clinical features of
Alzheimer-type dementia, particularly those related to
short-term memory."
[108g] Acetyl-L-carnitine: a drug able to slow the progress of
Alzheimer's disease? Carta A, Calvani M in Ann N Y Acad
Sci 1991;640:228-32 "A review of a series of controlled
clinical studies suggests that ALC may also slow the
natural course of AD."
[108h] Long-term acetyl-L-carnitine treatment in Alzheimer's
disease. Spagnoli A, Lucca U, Menasce G, Bandera L,
Cizza G, Forloni G, Tettamanti M, Frattura L,
Tiraboschi P, Comelli M, et al in Neurology 1991
Nov;41(11):1726-32 "In a double-blind,
placebo-controlled, parallel-group, randomized
clinical trial, we studied the efficacy of long-term
(1-year) oral treatment with acetyl-L-carnitine in 130
patients with a clinical diagnosis of Alzheimer's
disease. [.] Adjusting for initial scores with
analysis of covariance, the treated group showed
better scores on all outcome measures, reaching
statistical significance"
[108i] Double-blind parallel design pilot study of acetyl
levocarnitine in patients with Alzheimer's disease.
Sano M, Bell K, Cote L, Dooneief G, Lawton A, Legler
L, Marder K, Naini A, Stern Y, Mayeux R in Arch
Neurol 1992 Nov;49(11):1137-41 "These results suggest
that acetyl levocarnitine may retard the
deterioration in some cognitive areas in patients
with Alzheimer's disease"
[108j] Clinical and neurochemical effects of
acetyl-L-carnitine in Alzheimer's disease. Pettegrew
JW, Klunk WE, Panchalingam K, Kanfer JN, McClure RJ in
Neurobiol Aging 1995 Jan-Feb;16(1):1-4 "Compared to AD
patients on placebo, acetyl-L-carnitine-treated
patients showed significantly less deterioration in
their Mini-Mental Status and Alzheimer's Disease
Assessment Scale test scores. [.] This is the first
direct in vivo demonstration of a beneficial effect of
a drug on both clinical and CNS neurochemical
parameters in AD."
[108k] A 1-year multicenter placebo-controlled study of
acetyl-L-carnitine in patients with Alzheimer's
disease. Thal LJ, Carta A, Clarke WR, Ferris SH,
Friedland RP, Petersen RC, Pettegrew JW, Pfeiffer E,
Raskind MA, Sano M, Tuszynski MH, Woolson RF in
Neurology 1996 Sep;47(3):705-11 "The study suggests
that a subgroup of AD patients aged 65 or younger may
benefit from treatment with ALCAR whereas older
individuals might do more poorly."
[108l] Acetyl L-carnitine slows decline in younger patients
with Alzheimer's disease: a reanalysis of a
double-blind, placebo-controlled study using the
trilinear approach. Brooks JO 3rd, Yesavage JA, Carta
A, Bravi D in Int
Psychogeriatr 1998 Jun;10(2):193-203 "ALC slows the
progression of Alzheimer's disease in younger subjects
[age<61], and the use of the trilinear approach to estimate
the average rate of change may prove valuable in
pharmacological trials."
[108m] Acetyl-L-carnitine physical-chemical, metabolic, and
therapeutic properties: relevance for its mode of
action in Alzheimer's disease and geriatric depression.
Pettegrew JW, Levine J, McClure RJ in Mol Psychiatry
2000 Nov;5(6):616-32 "ALCAR is reported in double-blind
controlled studies to have beneficial effects in major
depressive disorders and Alzheimer's disease (AD)"
[108n] Thiamine and Alzheimer's disease. A pilot study. Blass
JP, Gleason P, Brush D, DiPonte P, Thaler H in Arch
Neurol 1988 Aug;45(8):833-5 "Global cognitive rating by
the Mini-Mental State Examination was higher during
three months with 3 g/d of oral thiamine hydrochloride
than with niacinamide placebo. Behavioral ratings,
however, did not differ significantly, nor did clinical
state when it was judged subjectively."
[108o] Preliminary findings of high-dose thiamine in dementia
of Alzheimer's type. Meador K, Loring D, Nichols M,
Zamrini E, Rivner M, Posas H, Thompson E, Moore E in J
Geriatr Psychiatry Neurol 1993 Oct-Dec;6(4):222-9 "we
examined the effects of 3 to 8 g/day thiamine
administered orally. Our results suggest that thiamine
at these pharmacologic dosages may have a mild
beneficial effect in dementia of Alzheimer's type."
[108p] Thiamine therapy in Alzheimer's disease. Mimori Y,
Katsuoka H, Nakamura S in Metab Brain Dis 1996
Mar;11(1):89-94 "Only mildly impaired subjects showed
cognitive improvement. Alzheimer patients' blood
levels of thiamine before the trial were within the
normal range."
[108q] Brain thiamine, its phosphate esters, and its
metabolizing enzymes in Alzheimer's disease.
Mastrogiacoma F, Bettendorff L, Grisar T, Kish SJ in
Ann Neurol 1996 May;39(5):585-91 "Clinical data suggest
that high-dose thiamine (vitamin B1) may have a mild
beneficial effect in some patients with Alzheimer's
disease (AD). [....] The TDP decrease could be
explained by a cerebral cortical deficiency in AD of
ATP, which is needed for TDP synthesis."
[109] Improvement of cognitive functions after
cobalamin/folate supplementation in elderly patients
with dementia and elevated plasma homocysteine. Nilsson
K, Gustafson L, Hultberg B in Int J Geriatr
Psychiatry 2001 Jun;16(6):609-14 "Patients with mild-moderate
dementia and elevated plasma homocysteine levels improved
clinically with increased test scores after vitamin
substitution, while severely demented patients and patients
with normal plasma homocysteine levels did not improve
clinically."
[108r] Impaired functioning of thermolabile
methylenetetrahydrofolate reductase is dependent on
riboflavin status: implications for riboflavin
requirements. McNulty H, McKinley MC, Wilson B,
McPartlin J, Strain JJ, Weir DG, Scott JM in Am J Clin
Nutr 2002 Aug;76(2):436-41 "The high tHcy concentration
typically associated with homozygosity for the 677C-->T
variant of MTHFR occurs only with poor riboflavin
status." The mutant, thermolabile version of MTHFR,
present in 10-15% of the European genotype renders the
co-enzyme FAD prosthetic group ~10 times more likely to
disassociate. Extra riboflavin stabilises MTHFR.
[108s] Riboflavin as a determinant of plasma total
homocysteine: effect modification by the
methylenetetrahydrofolate reductase C677T polymorphism.
Hustad S, Ueland PM, Vollset SE, Zhang Y, Bjorke-Monsen
AL, Schneede J in Clin Chem 2000 Aug;46(8 Pt 1):1065-71
"The riboflavin-tHcy relationship was modified by
genotype (P = 0.004) and was essentially confined to
subjects with the C677T transition of the MTHFR gene.
CONCLUSIONS: Plasma riboflavin is an independent
determinant of plasma tHcy."
Cheers, Michael C Price
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