Re: alcohol, lipo

[Guest guest]

This is correct, and it approximates how fats are metabolized. Alcohol

is calorie dense, after all, it is much easier set cognac on fire than

any soft drink for a reason.

Your body feels much the same way.

JB

> From what I remember from biochem, alcohol isn't

> metabolized into fat. It is first broken down to

> acetylaldehyde then to acetic acid, then to CO2 and

> keytones. It is true that consumption of large amounts

> of alcohol leads to accumulation of fat. I think this

> is primarily due to how caloric alcohol is. paul

[Guest guest]

I would agree with but add that his thoughts suggest a theory as to

how alcohol might contribute to fat accumulation or loss. But as Simon suggests

many people who drink do not develop body changes & I don't know of any

studies finding an association. Jules

<< I think it is pretty LIKELY that " excess " alcohol intake can contribute to

(but not cause) aspects of lipodystrophy. Depends a lot on things like your

metabolism (acetylation rate?) and liver function. Or if you are on a

particularly liver toxic drug like nevirapine. For an excellent review, see

http://www.elmhurst.edu/~chm/vchembook/642alcoholmet.html

They note the first chemical alcohol turns into is acetaldehyde and " a high

acetaldehyde level impairs mitochondria function. " So then you have an

issue here with alcohol+nukes=mito tox. PIs may also contribute.

You drink alcohol, you build up fats in the liver which are then excreted

into the blood. Among other problems. Add ritonavir for a delicious

cocktail from hell. The club kids, tho, seem to have dropped the PIs as

party favors...

M. >>

to get off this email list reply to jessie@... & put Unsubscribe in

Subject.

[Guest guest]

At 07:05 AM 8/11/2004 -0400, JuLev@... wrote:

>I would agree with but add that his thoughts suggest a theory as to

>how alcohol might contribute to fat accumulation or loss. But as Simon

>suggests

>many people who drink do not develop body changes & I don't know of any

>studies finding an association. Jules

Good question--so I looked around a bit....there are issues with alcohol.

Of course, we all know that people metabolize booze differently to begin

with. And second, a LOT depends on dose!

One issue that hasn't been touched on is ARV adherence. Gosh, a study shows

shockingly that if you're shit-faced, adherence levels might drop. Truly

shocking--but it does underscore another issue that people just need to be

real about. There's actually a number of studies related to substance use

and adherence if you go to PubMed and do a search on " alcohol, antiretroviral. "

Indeed--this is a rationale for improved access to treatment and care for

all substance abuse. Personally, I think a variety of models can be used

that address different needs. Harm reduction and AA-type programs are not

mutually exclusive!

As to interactions, the HORRORS of St. 's wort in interfering with

antidepressant sales--er--I mean " area under the curve " of indinavir are

widely known....but below is at least one study showing problems--in a rat

model--mixing alcohol with ritonaviar/saquinavir. " This study showed that

ethanol-intake decreases the bioavailability of SQV after oral

administration alone or with RTV. " Another study shows heavy drinking will

blunt immunological and virological responses to ARV.

Surprisingly, though, there are few studies evaluating the effect of

alcohol intake on ARV plasma levels.

M.

**

Samet JH, Horton NJ, Meli S, Freedberg KA, Palepu A. Alcohol consumption

and antiretroviral adherence among HIV-infected persons with alcohol

problems. Alcohol Clin Exp Res. 2004 Apr;28(4):572-577.

Clinical Addiction Research and Education (CARE) Unit, Section of General

Internal Medicine, Department of Medicine, Boston University School of

Medicine, Boston, MA, USA. jsamet@...

BACKGROUND: Alcohol abuse has been associated with poor adherence to highly

active antiretroviral therapy (HAART). We examined the relative importance

of varying levels of alcohol consumption on adherence in HIV-infected

patients with a history of alcohol problems. METHODS: We surveyed 349

HIV-infected persons with a history of alcohol problems at 6-month

intervals. Of these subjects, 267 were taking HAART at one or more time

periods during the 30-month follow-up period. Interviews assessed recent

adherence to HAART and past month alcohol consumption, defined as " none " ,

" moderate " , and " at risk " . We investigated the relationship between

adherence to HAART and alcohol consumption at baseline and at each

subsequent 6-month follow-up interval using multivariable longitudinal

regression models, while controlling for potential confounders. RESULTS:

Among the 267 HIV-infected persons with a history of alcohol problems who

were receiving HAART, alcohol consumption was the most significant

predictor of adherence (p < 0.0001), with better adherence being associated

with recent abstinence from alcohol, compared with at-risk level usage

(odds ratio = 3.6, 95% confidence interval = 2.1-6.2) or compared with

moderate usage (odds ratio = 3.0, 95% confidence interval = 2.0-4.5).

CONCLUSIONS: Any alcohol use among HIV-infected persons with a history of

alcohol problems is associated with worse HAART adherence. Addressing

alcohol use in HIV-infected persons may improve antiretroviral adherence

and ultimately clinical outcomes.

**

Shibata N, Kageyama M, Kishida T, Kimura K, Yoshikawa Y, Kuwahara T, Toh J,

Shirasaka T, Takada K. Pharmacokinetic characterization of a human

immunodeficiency virus protease inhibitor, saquinavir, during ethanol

intake in rats. Biopharm Drug Dispos. 2003 Nov;24(8):335-344.

Department of Pharmacokinetics, Kyoto Pharmaceutical University,

Yamashina-ku, Kyoto 607-8414, Japan. shibata@...

Throughout therapeutic drug monitoring of human immunodeficiency virus

(HIV) protease inhibitors in HIV-infected patients, it was found that

plasma concentrations of saquinavir (SQV) were reduced in patients who had

a habit of alcohol intake during double protease therapy with SQV and

ritonavir (RTV). This study confirmed the pharmacokinetic profiles of SQV

during ethanol intake in rats. After oral administration of SQV alone (20

mg/kg) in rats prepared by free access to 15% ethanol solution for 14 days

(day 14 rats), the area under the concentration vs time curves (AUC) showed

a significant decrease (p<0.01) in comparison with control rats from

0.78+/-0.10 to 0.38+/-0.03 microg h/ml. For intravenous administration of

SQV alone (5 mg/kg) to day 14 rats, the total body clearance increased

significantly by 1.4-fold (p<0.05), whereas for intracolonic administration

of SQV alone, no significant differences in the values of pharmacokinetic

parameters were found between control and day 14 rats. With RTV, which has

the strongest inhibitory effect on the CYP3A enzyme of the current HIV

protease inhibitors, the AUC values of SQV at RTV doses of 2 and 20 mg/kg

in day 14 rats also decreased significantly (p<0.01) from 1.30+/-0.06 to

0.57+/-0.05 microg h/ml and from 17.63+/-1.66 to 4.18+/-0.94 microg h/ml,

respectively, indicating that the degree of the decrease of AUC values

after oral administration with RTV after ethanol intake was larger than the

mono-therapy with SQV. This study showed that ethanol-intake decreases the

bioavailability of SQV after oral administration alone or with RTV. These

observations provide useful information for the treatment of HIV-infected

patients when they receive a combination therapy with SQV and RTV, and

arouse attention for the effects of alcohol intake. Copyright 2003

Wiley & Sons, Ltd.

**

Miguez MJ, Shor-Posner G, Morales G, A, Burbano X. HIV treatment

in drug abusers: impact of alcohol use. Addict Biol. 2003 Mar;8(1):33-37.

Department of Psychiatry and Behavioral Sciences, University of Miami

School of Medicine, Miami, FL 33136, USA. mmiguez@...

Studies of alcohol use in HIV-1 infected patients have resulted in

conflicting and limited information regarding prevalence, as well as impact

on HIV replication, disease progression and response to antiretroviral

therapy. Alcohol, drug abuse and past medical information, including

antiretroviral treatment, were obtained using research questionnaires and

medical chart review in 220 HIV-1 infected drug users. A physical

examination was conducted and blood was drawn to evaluate immune measures

and nutritional status. Heavy alcohol consumption, defined as daily or 3 -

4 times per/week, was reported in 63% of the cohort. Men (odds ratio (OR) =

2.6, 95% CI 1.13 - 5.99, p = 0.013), and participants between 35 and 45

years of age were three times more likely to be heavy alcohol users (p =

0.006 and 0.0009, respectively). Low serum albumin levels were more evident

in heavy alcohol users than non-drinkers (p = 0.003). Heavy alcohol users

receiving antiretroviral therapy were twice as likely to have CD4 counts

below 500 than light or non-drinkers (95% CI, 1 - 5.5, p = 0.03), and

highly active antiretroviral therapy (HAART)-treated heavy alcohol users

were four times less likely to achieve a positive virological response (95%

CI, 1.2 - 17, p = 0.04). Alcohol consumption is prevalent in our HIV-1

infected drug user cohort and significantly impacts both immunological and

virological response to HAART treatment.

[Guest guest]

At 10:22 PM 8/11/2004 +0000, you wrote:

>snip...

>And likewise, many people who DON'T drink, DO develop body changes --

>like me.

Indeed! Alcohol is not per se a *cause* but, if anything, a CONTRIBUTOR to

SOME aspects of lipodystrophy. Big distinction.

M.