Recent research suggests that once a week fasting plus
the lipid lowering drug acipimox can produce many of
the health benefits of calorie restriction (CR). See PUBMED:
15236765, 16973211, 15325580, 16874025, 16859482, 3978124, 12888255.
I find this approach attractive because I do not want
to deal with the hunger and weight loss of CR.

[I have been aware of the acipimox studies re autophagy for some time now. Both
CR and every other day fasting (EOD) have much data including lifespan studies
for many animal species to support their efficacy. Acipimox aided fasting has
relatively little study behind it, particularly no lifespan study with any
animal. I think that it is highly unlikely that this one upregulated axis
(autophagy) is responsible for all the benefits of CR and EOD. There are
additionally enormous numbers of benefits from having highly reduced amounts of
fat. Only today I read an article in Science News about a study showing that fat
cells excrete a substance that aids the development of cancer. Having a BMI of
20-21 is going to *always* be healthier than a greater one, unless the low BMI
has been caused by some disease process or unless one is going on a long trip to
the arctic, antarctic or some other desolate, remote wasteland. Since the
practice of CR can also be done without any hunger pangs (I and Kitty eat plenty
of food volume to satisfy us and even enjoy small dessert treats), I therefore
see no reason why anyone should be desperately trying to find ways to avoid it.
This having been said, I think that acipimox may well be a useful adjunct to CR
which will make its effects that much more beneficial without the CR having to
be so intense and for that reason I am planning to try it. --Paul]


Acipimox is not available in the USA, but it can be
ordered online (e.g www.1drug.com) I received
my 1drug order postmarked Thailand in only 11 days.
The trade name is Olbetam:
http://www.intekom.com/pharm/pharmaca/olbetam.html

One week ago I tried fasting for 24 hours without taking any
acipimox, and I did not find it too difficult. I took only water
from 19:00 until 19:00 the next day.

[This appears to be in contradiction to your statement above that you do not
want to "deal with the hunger" of CR, since the simple regimen of doing without
breakfast every other day would be one way of practicing CR. Another very simple
way is to eat only twice daily and/or cut the size of your meals - eat slowly
until you no longer feel hungry and then stop. Drinking green tea between meals
easily staves off any hunger until the next meal either 8-9 hours later if that
meal is dinner, or 14-15 hours later if that meal is breakfast. --Paul]

[The best ways I have found to reduce the annoyance of hunger is to be busy at
tasks that call for concentration and to have plenty of green-rooibos tea
available (with lemon for my taste preference). Boredom or monotonous
tasks/activities are notorious for increasing one's perception of an empty
stomach. **Kitty]

[In the studies showing benefits of weekly fasting or every other day fasting
the regimens have involved full days without food. The regimen you describe on
the other hand where you fast from 19:00 until 19:00 the next day is equivalent
to eating once daily, not fasting a whole day. Let's say a person regularly
wakes up at 8.00am and goes to sleep at 12.00am, eats breakfast at 9.00am and
eats his last meal of the day at 8.00pm. If he fasts for a full day then he will
be fasting from 8.00pm to 9.00am two days later, a total of 36 hours. You on the
other hand are only fasting for 24 hours so the benefit you get might be
considerably less than if you fasted for a whole day. The relative difference is
even greater if you consider the fact that you will not reach a fasted state
until a few hours after eating your last meal so the actual time spent in a
fasting state will be a few hours less than the time frame between the meals.
Fasting for 24 hours the way you are doing it will most certainly be very
beneficial for you, I just wanted to point out that it is not equivalent to
fasting a whole day and the benefits will likely be less than if you took a
whole day off food. -°Olafur]


I also tried one 250 mg
capsule of acipimox with a meal to make sure I did not have
a rare allergic reaction.

[That was a wise action. --Paul]


Last Friday I started my first acipimox fast:
* dinner at 19:00, then started water fast
* one 250mg capsule at 22:00
* one 250mg capsule at 6:00
* one 250mg capsule at 12:00
* broke fast at 19:00 with dinner.

[From where did you get this regimen for taking acipimox for promotion of
autophagy? My guess is that the capsule at 22:00 would be largely wasted. It
also appears that you are going to bed only 3 hours after eating. This is a
mistake. From the point of view of hormone production and other physiological
activities that take place during sleep the body should be in a fasted state
right at the start of sleep. Therefore, one should always finish eating at least
4 hours before sleep and preferably 6 hours. If you want to take 3 capsules on
the day of the fast, then I suggest that 6:00 (presumably your rising time).
10:00 AM and 2:00 PM would be better, with dinner no later than 6:00 PM --Paul]

[There is one reason to think the capsule at 22.00 would not be largely wasted.
It is well known that insulin inhibits autophagy although in some cases it can
also stimulate it, and as I've posted on the sci.life-extension group lowering
of insulin level probably plays a role in the effect of acipimox on autophagy.
Acipimox has been shown to lower insulin levels, but when insulin levels are
already very low it doesn't seem to lower it any further. In the full text of
PMID: 9753300 (which is free through pubmed BTW) acipimox given to subjects
fasted overnight or fasted for 24 hours did not appear to reduce their insulin
levels probably because they were already very low after the fasting. So with
respect to acipimox's effect on insulin levels it would probably be of most
benefit at the start of the fasting when insulin levels have not fallen far down
yet. Taken at that time it might help reduce insulin levels faster after the
meal and reaching a state of higher autophagy sooner. -°Olafur]

[That means that taking acipimox only 3 hours after eating would also compensate
for the lack of time after eating before going to sleep, since the low insulin
level is essential for the sleep benefits to which I was referring. However, I
still think that it would be even better to eat 4-6 hours before sleep and be in
a naturally fasted state at sleep time. In addition, the purpose and effect of
acipimox is not only or even mainly to lower insulin, otherwise it would be of
little value to take it during the next daytime when already in a fasted state.
BTW, don't forget that it will also be best to exercise just before dinner,
particularly on those days when you do not eat breakfast and take acipimox.
--Paul]


I had no problems except for slight headache in afternoon.
I was not too hungry either. I did feel more tired than
usual in the late evening, so I went to bed earlier and
slept longer than normal. I am not sure this was
connected to the fast or the acipimox, except that I
do not remember feeling tired after my non-acipimox fast.

[This feeling can vary from time to time. So you would need to try these with
and without variations several times to see if there is a real co-relation with
tiredness or not. --Paul]


I have a report from another person who has tried the
acipimox fast that they experienced increased hunger in
the afternoon that might to be caused by the lipid lowering
effect of acipimox. However, I did not experience this.

Barring complications I plan to continue these once weekly
fasts with acipimox for 6 months when I have a yearly
physical that might indicate health improvements such as
lower lipid levels. I am 62 yo, 180 lb, 6'1" and, I am in
excellent health.

[That will certainly be interesting to see. One of the problems with this
regimen (as with so many others, particularly those involving nutrients) is that
there is often very little way in the short term that one can detect whether or
not the regimen is having any beneficial effect. This is probably why so many
people do not maintain such regimens for very long and constantly seek others,
that usually turn out to be equally as equivocal. Instead for long term human
benefit, one must learn to understand and have confidence in the study results
for shorter lived animals or for shorter times with diseased humans, and/or in
the mechanisms behind the regimens. --Paul]


If anyone else has experience with acipimox fasting, I would
like to share experience with them.

[When I and Kitty try it, we will of course post our experience here and on our
website. However, since we are in the midst of several other alterations and
trying to reach a steady state with all parameters in a good state, using
acipimox may have to wait many months yet. --Paul]


Ciao,

Dave

PS Kitty: Yes, the picture on my Yahoo profile is from the
Andes. I was standing a "The Gate of the Sun", a spectacular
overlook at Machu Picchu in Peru, after a 4 day trek
along the Inca trail. Last month I climbed the volcano
Cotopaxi (5,897 m or 19,347 ft) in Ecuador:
http://www.infiltec.com/galapagos/sIMG2524.jpg
One of my hobbies is adventure travel.

[Thanks, Dave, for detailing the photo location. This one and your more recent
sound very interesting and definitely adventuresome. The photo in the link
appears to show a higher level of risk than I or Paul are willing to take.

Both of us enjoy hikes but ours in the Arizona deserts and slightly higher
elevations, as well as those in woods of Harcourt Park in Ontario, (photos of
various areas available - http://morelife.org/personal/photos/ ) are as far as
we will likely go for awhile. **Kitty]