On Mon, 23 Jun 2003 16:13:52 -0700, Brian Mailman
<bmailman@sfo.invalid> wrote:

Some data below.
George M. Carter

****
Haas DW, Zala C, Schrader S, Piliero P, Jaeger H, Nunes D, Thiry A,
Schnittman S, Sension M. Therapy with atazanavir plus saquinavir in
patients failing highly active antiretroviral therapy: a randomized
comparative pilot trial. AIDS. 2003 Jun 13;17(9):1339-1349. For the
Protocol AI424-009 Study Group.

aVanderbilt University School of Medicine, Nashville, Tennessee,
the bComprehensive Care Center, Nashville, Tennessee, USA, the
cFundacion Huesped and Department of Microbiology, School of Medicine,
University of Buenos Aires, Argentina, the dHCRN/Montrose Clinic,
Houston, Texas, the eAlbany Medical College, Albany, New York, the
fMUC Research, Inc., Munich, Germany, the gInstituto De Infectologia
Emilio Ribas, Sao Paulo, Brazil, the hBristol-Myers Squibb Company,
Wallingford, Connecticut and the iNorth Broward Hospital, Ft.
Lauderdale, Florida, USA.

OBJECTIVESTo assess the safety, efficacy of atazanavir (400 and
600 mg)/saquinavir (1200 mg) once daily versus ritonavir/saquinavir
(400 mg/400 mg) twice daily with two nucleoside reverse transcriptase
inhibitors (NRTIs) in highly active antiretroviral therapy failure.
DESIGN AND METHODS Randomized, multinational, 48-week, pilot trial
with antiretroviral-experienced patients having at least 1000 HIV-1
RNA copies/ml, 100 x 106 CD4 cells/l (75 x 106 cells/l without AIDS
diagnosis) and virological response to a prior regimen. Efficacy was
evaluated by HIV-1 RNA and CD4 cell changes from baseline to 48 weeks.
RESULTSComparable efficacy across groups at 48 weeks: mean HIV-1 RNA
decreases, 1.44, 1.19 and 1.66 log(10) copies/ml (P = NS) and
comparable virological response (> 1.0 log(10) decrease HIV-1 RNA or
HIV-1 RNA < 400 copies/ml) was achieved in 41, 29 and 35% (P = NS);
and mean CD4 cell increases, 109, 55 and 149 x 106 cells/l in
atazanavir 400-mg, atazanavir 600-mg and ritonavir groups,
respectively. There were fewer adverse event discontinuations in the
atazanavir groups (9%, 11%) versus the ritonavir group (30%) and
atazanavir lacked adverse effects on lipids. In the atazanavir 400-mg,
atazanavir 600-mg and ritonavir groups the mean changes from baseline
at 48 weeks in fasting low-density lipoprotein (LDL) cholesterol
concentrations were -0.6, -6.7 and 23.2%, respectively and in fasting
triglyceride concentrations they were -4.8, -27.1 and 93.0%,
respectively (P < 0.05, LDL cholesterol; P < 0.001, fasting
triglyceride; atazanavir/saquinavir versus ritonavir/saquinavir).
CONCLUSIONSIn antiretroviral-experienced patients, once-daily
atazanavir/saquinavir was safe and well tolerated, showing comparable
efficacy to twice-daily ritonavir/saquinavir, both with two NRTIs.
Small lipid changes from baseline with atazanavir/saquinavir were not
clinically significant in comparison with the prompt, marked and
sustained changes of a magnitude suggesting clinical relevance
achieved in the ritonavir/saquinavir group.

GMCarter wrote:
Cool, thanks. My total cholesterol is under control (niacin, 2000mg 3x
day, lopid/gefimbrozil and mevacor), tryglycerides under control, but
LDL is still waaay too high. As is homocysteine, my doc is telling me
to take a folic acid supplement for that.

B/

On Wed, 25 Jun 2003 10:11:27 -0700, Brian Mailman
<bmailman@sfo.invalid> wrote:

Good for your doc! He's correct. Consider taking it with B12 too.
Actually, take it as a B-complex, you should get plenty (like a "B-50"
type). It may not help on its own (see 2nd abstract) for future CHD,
which is why I think the B complex approach makes more sense. Indeed,
the B's are critical co-enzymes for many reactions in the body, a lot
having to do with mitochondrial function and production of ATP, which
is significantly impaired by nukes, as well as HIV.

Plus, I think either carnitine (3g/d) or acetylcarnitine makes a lot
of sense. And NAC. Those just make tons of sense.

For my hep C, and for similar underlying pathogenesis reasons of
oxidative stress, I take an iron-free multi, a B complex, NAC and some
other stuff.

First abstract shows effect of folic acid on homocysteine. Second
suggests possibly little clinical benefit on one parameter studied.
Third looks at use of more than just one vitamin. (Vitamins work in
concert; what surprises me these days is the extent to which a single
vitamin will have a lot of beneficial effect. They should be used in
combination in doses that do not produce toxicity.)

George M. Carter

****
J Intern Med. 2003 Jul;254(1):67-75. Links

Effect of vitamins and aspirin on markers of platelet activation,
oxidative stress and homocysteine in people at high risk of dementia.

[No authors listed]

VITAL Trial Collaborative Group. Effect of vitamins and aspirin on
markers of platelet activation, oxidative stress and homocysteine in
people at high risk of dementia. J Intern Med 2003; 254:-. OBJECTIVES:
To examine the association of cognitive impairment with platelet
activation and reactive oxygen species and total homocysteine levels;
and to assess the biochemical efficacy of treatment with aspirin and
vitamin supplements in people at high risk of dementia. SUBJECTS:
People with dementia or mild cognitive impairment. DESIGN AND
INTERVENTION: In a 2 x 2 x 2 factorial design trial, 149 people at
high-risk of dementia were randomized to receive either low-dose
aspirin (81 mg) or placebo; and folic acid (2 mg) plus vitamin B12 (1
mg) or placebo; and vitamins E (500 mg) plus C (200 mg) or placebo.
Participants were seen twice before and once after 12 weeks of
treatment. MAIN OUTCOME MEASURES: At each visit, participants had
their cognitive function assessed and had blood collected for
homocysteine, folate and vitamin B12 determination and urine collected
for markers of platelet activation (11-dehydro-thromboxane B2) and
reactive oxygen species (8-epi-PGF2alpha). RESULTS: Prior to
treatment, cognitive function was inversely related with homocysteine
and with urinary thromboxane and isoprostane, and these associations
were independent of age. Aspirin was associated with a median
reduction in 11-dehydrothromboxane B2 of 73% (P < 0.001). B-vitamins
lowered plasma homocysteine concentration by 30% (P < 0.0001) and
antioxidant vitamins lowered isoprostane excretion by 26% (P < 0.1).
No effect of treatment on cognitive function was detected.
CONCLUSIONS: Aspirin and B-vitamins were effective in reducing
biochemical factors associated with cognitive impairment in people at
risk of dementia. Large-scale trials are now required to assess the
relevance of aspirin and B-vitamins for the maintenance of cognitive
function in people at risk of dementia.
****

J Am Coll Cardiol. 2003 Jun 18;41(12):2105-13. Related Articles, Links
Click here to read
Secondary prevention with folic acid: effects on clinical
outcomes.

Liem A, Reynierse-Buitenwerf GH, Zwinderman AH, Jukema JW, van
Veldhuisen DJ.

Department of Cardiology, Oosterschelde Ziekenhuizen, Goes, The
Netherlands. anho@zeelandnet.nl

OBJECTIVES: We sought to conduct a randomized trial with folic
acid 0.5 mg/day in a patient population with stable coronary artery
disease (CAD). BACKGROUND: Folic acid has favorable effects on
vascular endothelium and lowers plasma homocysteine levels. In
addition, homocysteine appears to be an independent risk factor for
atherosclerotic disease. However, the value of folic acid in secondary
prevention had seldom been tested. METHODS: In this open-label study,
593 patients were included; 300 were randomized to folic acid and 293
served as controls. Mean follow-up time was 24 months. At baseline all
patients had been on statin therapy for a mean of 3.2 years. RESULTS:
In patients treated with folic acid, plasma homocysteine levels
decreased by 18%, from 12.0 +/- 4.8 to 9.4 +/- 3.5 micromol/l, whereas
these levels remained unaffected in the control group (p < 0.001
between groups). The primary end point (all-cause mortality and a
composite of vascular events) was encountered in 31 (10.3%) patients
in the folic acid group and in 28 (9.6%) patients in the control group
(relative risk 1.05; 95% confidence interval: 0.63 to 1.75). In a
multifactorial survival model with adjustments for clinical factors,
the most predictive laboratory parameters were, in order of
significance, levels of creatinine clearance, plasma fibrinogen, and
homocysteine. CONCLUSIONS: Within two years, folic acid does not seem
to reduce clinical end points in patients with stable coronary artery
disease (CAD) while on statin treatment. Homocysteine might therefore
merely be a modifiable marker of disease. Thus, low-dose folic acid
supplementation should be treated with reservation, until more trial
outcomes become available.



***
Transplantation. 2003 May 15;75(9):1551-5. Related Articles, Links
Vitamin supplementation reduces the progression of atherosclerosis
in hyperhomocysteinemic renal-transplant recipients.

Marcucci R, Zanazzi M, Bertoni E, Rosati A, Fedi S, Lenti M,
Prisco D, Castellani S, Abbate R, Salvadori M.

Surgical and Medical Critical Care, Clinica Medica Generale e
Cliniche Specialistiche, University of Florence, Italy.

BACKGROUND: We previously demonstrated among renal-transplant
recipients (RTRs) a high prevalence of hyperhomocysteinemia, which
might account for their elevated cardiovascular risk. The purpose of
our study was to document, in hyperhomocysteinemic RTRs, the effect of
vitamin supplementation on carotid intima-media thickness (cIMT),
which is an early sign of atherosclerosis. METHODS: A total of 56
stable hyperhomocysteinemic RTRs were randomly assigned to vitamin
supplementation (folic acid 5 mg/day; vitamin B(6) 50 mg/day; vitamin
B(12) 400 microg) (group A) or placebo treatment (group B) for 6
months. All subjects underwent cardiovascular risk-factor assessment,
including fasting homocysteine (Hcy) levels assay, and high resolution
B-mode ultrasound to measure the intima-media thickness of common
carotid arteries, at time of enrollment and after 6 months. RESULTS:
Fasting Hcy levels markedly decreased in group A after treatment (21.8
[15.5-76.6] micromol/L vs. 9.3 [5.8-13] micromol/L; P<0.0001), whereas
no significant changes were observed in group B (20.5 [17-37.6]
micromol/L vs. 20.7 [15-34] micromol/L; P=not significant). In group
A, cIMT significantly decreased after treatment (0.95+/-0.20 mm vs.
0.64+/-0.17 mm; P<0.0001). All except one patient showed a reduction
of cIMT and the mean percentage of cIMT decrease was -32.2+/-12.9%.
Patients with methylenetetrahydrofolate reductase (MTHFR) C677T +/+
genotype, with higher Hcy levels, had the major percentage of decrease
of Hcy with respect to the other genotypes (mean decrease: MTHFR +/+
74.8+/-5.7%; MTHFR +/- 58.1+/-10%; MTHFR -/- 56.3+/-8.6%). In
hyperhomocysteinemic patients without vitamin supplementation (group
B) we documented a significant increase in cIMT after 6 months
(0.71+/-0.16 mm vs. 0.87+/-0.19 mm; P<0.05). In 19 of 28 subjects we
observed an increase in cIMT, and in 9 of 28 the cIMT was unmodified.
The mean percentage of cIMT increase was + 23.3+/-21.1%. CONCLUSIONS:
Our results demonstrate a beneficial effect of the treatment of
hyperhomocysteinemia by vitamin supplementation on cIMT in a group of
RTRs.

GMCarter wrote:
Yeah, seems he's having an attitude adjustment to "nutraceuticals." He
used to mutter things about "that's harmless, go ahead if you want but
don't expect anything." Now he's moving toward giving supplement advice
pro-actively. Maybe. He still won't acknowledge my cd4s were scooting
along at mid-300s for 3 years and after 4 months of Juven bumped up to
high 600s (no other change in regimen).

He says, "if you die of CHD, it'll be a black mark on my book."

Yah, that's what he said when I asked him how much and how often--"go to
the pharmacy, we've got OTC folic acid with b-complex there."

Again, yar. When I was in the adefovir study (before I went into kidney
failure from it, reversed with stopping it) my carnitine was 1/2 what it
should be. But he won't prescribe it and with limited income I can't
afford the OTC. I'm thinking next set of labs to ask for a carnitine
test and push for a script as long as he's more amenable to
supplementation.

Milk thistle, if I remember?

B/

On Fri, 27 Jun 2003 10:17:03 -0700, Brian Mailman
<bmailman@sfo.invalid> wrote:


Yikes!! Now go back and kick his ass. LOW Carnitine is LISTED in the
PDR as the indication for prescribing it. He SHOULD!!! The stuff is
expensive. Many docs prescribe it now. And it can have a good effect
on triglycerides for some--it's worth a try.

Yes. I am not HIV+ (last I checked) and in any event not on ARV or
other pharmaceuticals. I also take a Chinese blend of botanicals
known as Hepato-C, that I attribute to having helped normalize my
liver enzymes. That was on a couple of blood works.

However, for about a year, I haven't been able to establish whether
the response is durable as I had to essentially choose between
insurance premiums which I couldn't really afford and completely
sacrificing supplements or taking supplements that would also leave me
enough money to live on, I had to let the insurance go.

George M. Carter

GMCarter wrote:

They certainly do get ya coming and going.

B/