Dr Davis,

Please give us your take on KIF6.  I know that the data in some ways is preliminary.  All that I can seem to find is the 3 JACC articles in 1/08.  2 of them simply show a high prevalence of the arg/trp or arg/arg variant. But the study showing a statistical difference in MI/ Cardiac Death in as little as 30 months comparing 40 pravachol vs 80 lipitor is impressive.  Statins do save lives so they are ok with me.  It is just that the number needed treat/ number needed to harm ratio is too high.  KIF6 has the potential to cut the number needed to treat in half.

Co-incidentally I am about to go off my Crestor (40mg) for a "rest". I need to loose weight (5'7" and 195lb) but when I started my p90x program, I found that those annoying muscle aches in my left arm and right hand were such that I could not do a single pull up.  My Dr. asked that I stay on the higher dose of Crestor and supplement with CoQ10.  I will add CoQ10 to the fish oil, Niacin and vitamin D I am taking.  I'm going to start Vitamin K2 supplementation too (Canada does not allow high dose for some strange reason). But more than anything, recognizing some of the side effects I have read here, I think a break from Crestor is  overdue for me.

there is no shortage of criticism on this blog of statins and they certainly are over prescribed.  the real question is: when and only when should they be tried?  It would be helpful if you posted on this now that you have carefully gone in to some of the negatives of statins, but also, acknowledged their value.

What about women with high cholesterol without (overt) heart disease or a family history of heart disease? Some say that older women with high cholesterol live longer and better. This certainly has been true in my family. The women live to 90's without heart disease, total cholesterols 220-250 LDL certainly higher than the current "normal/optimal" but with high HDL and low triglycerides.

Hey there, Dr. Davis. Where are all the testimonials from people who have no side effects from statins and are doing just fine with lowered LDL levels?

Or does your profit incentive prohibit you from being fair and balanced, just like the pharmaceutical industry.

I dare you to publish this post. Not doing do will reveal your true intentions.

Steve and Bruce--

I am mindful of the fact that representatives of the pharmaceutical industry troll the blogosphere and internet in order to post comments to counter the rapidly growing rejection of the statin franchise. If you work for Pfizer, AstraZeneca, et al, I would kindly ask you to mind your own business.

If you do not, then please recognize that what I say is said because of the overwhelming influence of the drug industry. It is a David vs. Goliath world. The drug industry does not need to be defended. They would willingly take as much of your money and your insurer's money as possible. Their goals have little to do with health, but everything to do with profit.

If you have fallen victim to their brand of Kool Aid, then perhaps it's time for a little reality check.

Yet more scary but interesting stuff!

I was put on lipitor but had a (rare but reported) side effect that in retrospect was BG lowering over and above the reactive hypos I was already suffering

Switched to simvastatin and have been on it ever since, it appears to do exactly what it says on the tin, halves my LDL without affecting the lethal trigs and HDL (diet fixed them)

NOW I'm wondering if my apparent senility attacks are in fact not due to advancing age. In typing this I have already done several letter pair reversals. I actually forgot to make an appointment for my blood tests which ironically I am now going to blame on the statin (grins) I was going to drop them for a month prior to the next tests but maybe I am going to drop them now.

Why? I have also begun getting tinnitus. The trigger factor appeared to be NSAIDS, even ointment was bringing it on. Now I'm getting it even without these.

I suspect statin side effects are still rare compared to the percentage of people who don't get them BUT with an increasing statinised population there's a low percentage of a huge population now reporting in, hence the apparently increased incidence.

DR Davis:
i do not work for big pharma or any medical or health related profession, and am only interested when statins should be prescribed since my NMR results showed high small LDL despite my not eating wheat,using fish oils, taking D3 as you suggest. Since my Doc says statin time, i am only trying to get the best info in light of all negative publicity.
Perhaps you read my comment to fast; it was not advocating them, but asking since you in your post allude to possible cases when it should be used.  Your comment to me is therefore way out of line.

I fall on the side of believing that statins should never be prescribed.  From my understanding, while there's a slight indication that they can reduce cardiovascular events, they DO NOT reduce all-cause mortality.  This strongly suggests that they are mostly ineffective at doing what they're touted to do, and they introduce a new set of problems that can reduce the patients quality and length of life.

The purported benefits of statins, in all cases, can be beaten handily by a change of diet and supplements.

I think your personal practice is a testament to this, and yet you still leave several diet and supplement tactics on-the-table that could improve the results you could achieve. (I base this on reading every entry in your blog, and listening to your podcasts with Jimmy Moore.)

I love that you're well ahead of 99.999% of the other cardiologists.

I would like to know of any situation that you can quickly describe in which a statin makes sense.  I have an open mind about this, and perhaps you can convince me that such cases exist.

Stop press, dropped last night's statin and already the tinnitus is much reduced. It was never bad but was increasing and I thought its prevalence at night was due to quietness of the environment not to the fact I'd just taken the statin.

Now in the past I'd dropped the things for a month on month off trial which is why I am confident there were THEN no noticeable side effects.

SSRI poop-out is a well known phenomenon and the explanation used to be that while they upregulated serotonin, over time they would then downregulate dopamine in some individuals.

Most statin side effects I've heard of seem to be fairly instant, now I'm wondering if there's a similar temporal effect whereby some side effects don't develop for months or even years. This might explain why reports of problems are increasing over time even faster than the population is becoming statinised

Just wanted to report back on the break I have taken from 40mg Crestor.  Although I posted here on March 1st, I was really hesitant to stop since I was off on a business trip and not going to be too careful about diet.

Anyhow, full 10 days without Crestor and I have ZERO arm aches and have no issue doing chin ups (well, I can do some and all without the sharp "broken bone" pain).

I know I'm going to end up back on Statins as I really hate eating meat, but while I am trimming down, I will stay off them for maybe 3 or 4 months then get a blood test before asking the primary care phys for a dose recommendation.

An Appeal for Support and Conformation of MRI Results

My daughter has lived with ALS-like symptoms for almost 3 years. The worst of the symptoms began when her simvastatin was increased to 80mg in 2008.
Her MRIs show LESIONS in the brain stem, specifically in the PONS area of her brain.
Of course, her 4 physicians refuse to believe that a statin is involved. They are all satisfied with the diagnosis of “Ataxia”.

My Appeal is to all those who are/were on statins and have similar brain lesions as shown and documented in MRIs. Please reply here, or contact her father directly: Dr Stephen Arvay, stephenx11@cogeco.ca

What I am advocating is that statins be used carefully, after all efforts at correction of lipid/lipoprotein patterns have been made, with an assessment of true coronary risk (not such nonsense as the Framingham score). A more reasonable application of statin drug prescription would shrink the market from its current $27 billion to a tiny fraction of that.

when taking statins, follow doctors advice, take the drugs according to doctors prescription, the  drug carefully to be safe.

Finlaly! This is just what I was looking for.

Ya learn something new evreyady. It's true I guess!

ky8G9W , [url=http://nxiychlujevf.com/]nxiychlujevf[/url], [link=http://ijpwiebyjghx.com/]ijpwiebyjghx[/link], http://ozrkczkuzcwy.com/

Then again it maybe this patient was using too low a dose?
And what else was the patient ingesting? And there is the issue of which class lipid abnormality this patient had.

In my comments below I've included some abstracts of some human based studies that suggest inositol hexanicotinate isn't useless for altering serum lipid levels.


If we assume for a moment the validity of your anecdote,
I won't call inositol hexanicotinate worthless rather I would suggest it might have has narrower scope of uses not including the altering
blood lipids.  Not everyone (me) takes large doses niacin for it lipid altering properties. Consider Kaufman's work with niacinamide in patients
with degenerative arthritis. He used doses of 1.5 to 4 grams and
claimed increased joint mobility after a couple of months.
In my experience, niacin also works as well as niacinamide
against my pains in and around my joints. Its benefits against the pain come about gradually but
nonetheless are quite effective for me.

The flush can be pretty nasty if one isn't careful about the dose.
I know when I mixed niacinamide and niacin in the past I seemed
to have somewhat more flushing. I took niacin for several years
until it started to be trigger atrial premature beats.
I'll comment further in this posting on a way around these adverse effects of niacin.


Inositol hexanicotinate maybe superior provided one chooses
the right patients? Please see the second abstract below.
----------------------------------------------------


1: Eur. J. Clin. Pharmacol. 1979 Aug;16(1):11-5.


Nocturnal inhibition of lipolysis in man by nicotinic acid and derivatives.


Kruse W, Kruse W, Raetzer H, Heuck CC,
Oster P, Schellenberg B, Schlierf G.


The effect of nicotinic acid and several derivatives
on the nocturnal level of free fatty acids was studied
in 12 healthy young women and men. Free fatty acids
are an important precursor of plasma triglycerides
and their concentration is highest at night.
The drugs used were nictinic acid, beta-pyridyl-carbinol,
mesoinositol hexanicotinate and xantinol nicotinate.
The highest plasma nicotinic acid level was observed
with beta-pyridyl-carbinol, but significant reduction in
free fatty acids during the entire night was only
achieved with inositolhexanicotinate and
xantinol nicotinate. There was no correlation between
the plasm levels of free fatty acids and nicotinic
acid at any sampling time. If prolonged reduction
in free fatty acid concentration is desired in the therapy of
hyperlipidemias, the inositol and xantinol esters of
nicotinic acid appear to be superior to the other preparations.


PMID: 499296 [PubMed - indexed for MEDLINE]
========================================


Inositol hexanicotinate seems to work to lower some
blood lipids in this next human study and granted
another drug is also involved.
-------------------------------------------------------------
1: Arzneimittelforschung. 1979;29(10):1621-4.


[Treatment of various types of hyperlipoproteinaemia with
a combination of Mg-chlorophenoxy-isobutyrate and
mesoinositol-hexanicotinate (author's transl)]


[Article in German]


Bolzano K, Krempler F, Haslauer F.


50 patients with different types of hyperlipoproteinaemia
were treated with a combination of Mg-chlorophenoxyisobutyrate
(700 mg) and mesoinositol-hexanicotinate (500 mg) (Atroplex)
twice daily. 7 patients had type IIa, 39 patients type IIb
or IV and 4 patients type V. After a period of one
month without any treatment the patients were treated
during two months. While the effects of this combination
on cholesterol of type IIa patients was poor, the
drug had an excellent lipid-lowering effect in the patients
with type IIb, IV and V. After 14 days' treatment the
plasma cholesterol and triglyceride levels in
patients of type IIb or IV were significantly lowered.
This effect became even more pronounced after
one-month treatment. There was no significant difference
between the effect of one-month treatment and
that of two-month treatment. About two-thirds of the
patients of type IIb or IV were responders. No serious side
effects could be observed during our study.


Publication Types:
    English Abstract


PMID: 583231 [PubMed - indexed for MEDLINE]
--------------------------------------------------
So could it have been that this patient had one of the classes
of hyperlipidemic disorders such as type 1, type
2-a or type 3 for which inositol hexanicotinate
maybe ineffective?


=====================================================
It may have other uses see next paper.
-------------------------------------


1: Clin. Rheumatol. 1988 Mar;7(1):46-9.


A double blind randomised placebo controlled trial
of hexopal in primary Raynaud's disease.


Sunderland GT, Belch JJ, Sturrock RD,
Forbes CD, McKay AJ.


University Department of Surgery,
Glasgow Royal Infirmary, Scotland.


The peripheral vasospastic symptoms associated
with Raynaud's disease continue to
be an unsolved clinical problem. Hexopal
(Hexanicotinate inositol) has shown
promise in uncontrolled studies and its use in
patients with Raynaud's disease may reduce such
vasospasm. This study examines the effects of
4 g/day of Hexopal or placebo, during cold weather,
in 23 patients with primary Raynaud's disease.
The Hexopal group felt subjectively better and
had demonstrably shorter and fewer attacks of
vasospasm during the trial period.
Serum biochemistry and rheology was
not significantly different between the
two groups. Although the mechanism of
action remains unclear Hexopal is safe
and is effective in reducing the vasospasm
of primary Raynaud's disease during the winter months.


Publication Types:
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't


PMID: 3044673 [PubMed - indexed for MEDLINE]
====================================================
: J. Int. Med. Res. 1979;7(6):473-83.


An experimentally controlled evaluation of the effect
of inositol nicotinate upon the digital blood flow
in patients with Raynaud's phenomenon.


Holti G.


The vaso-active effects of inositol nicotinate (Hexopal)
were investigated in thirty patients with primary and
secondary Raynaud's phenomenon using several
non-invasive experimental techniques under
controlled conditions. The earlier formed impression
that this drug requires a prolonged 'build-up' period was
confirmed. Recording the time required to induce
Raynaud's phenomenon as well as assessments of total
and nutrient digital blood flow showed significant
beneficial therapeutic effects upon the skin's
microcirculation by inositol nicotinate. This study
suggests that the therapeutic effect of this drug is not
merely due to vasodilation but that other mechanisms
such as enhanced fibrinolysis and lowering of
serum lipids may play a significant part in its
overall effect. Smokers responded slower than non-smokers,
but even elderly patients with longstanding vasospastic
disease showed measurably improved digital circulation.
Unlike some other drugs in this field inositol nicotinate was found
to be effective orally and to be devoid of unwanted side-effects.
However, in the majority of patients it failed to
abolish their increased vascular spasm although
it diminished it significantly in most. It appears
to be a safe and well tolerated drug, which,
together with other symptomatic measures, merits
to be used in the management of vasospastic
disease of the extremities even in the
presence of partial obliteration of the microcirculation.


Publication Types:
    Clinical Trial
    Randomized Controlled Trial


PMID: 391622 [PubMed - indexed for MEDLINE]
=======================================


Perhaps what is needed is a larger dose in comparison
to other forms of niacin?

---------------------------------------------
Now to expand the topic to plain old TR niacin and betaine.
---------------------------------------------

Timed release niacin as I recall is twice a effective
as simple niacin in lowering lipids and twice as toxic.
So it seems come out about even if one takes a half
the dose of TR niacin.

Of course, what I'd love to test is niacin in its various forms
along with trimethylglycine (TMG) aka betaine. And I won't  
just consider lipid level effects but also the effects on
osteoarthritis and other joint pains.

Why do I mention betaine? I know from personal experience
high doses of betaine along with niacin pretty well blocks
the flushing effect as well as completely
blocking the atrial premature beats (AVB) that I would get
when taking either high dose niacin or niacinamide.
I had taken niacin at a rather high doses for about 5 or 6 years
back a couple of decades ago and then I started
to get the AVBs when I tried to
resume the use of doses above 100 milligrams.
Now of course provided I take the betaine I don't have
this problem. However, I do get AVBs if I don't use the
betaine and only take the niacin.
Granted some suggest niacin lowers the lipid levels
by "stressing" the liver so if betaine blocks
this effect it maybe contraindicated for the purpose
of changing lipid levels.
Here are Pubmed ID numbers, for some papers that
reflect similar thinking using betaine to reduce
the toxicity of high dose B-3.
PMID: 10985907
PMID: 17156888

--------------------------------------------

I'd be interested in your comments on the points of
theory and science. I am not looking for personal
advice. A number of people including myself
are discussing the niacin topic on the
Usenet forum....sci.life-extension (which
is also available by way of the Google Group
Archive for free provided you have a throw away email address).
Someone else referred to your blog comments and yet
another person proposed contacting you for a comment.
I was elected to contact you.
The group/forum members were interested as to whether there is
more to your anecdote concerning the possible ineffectiveness
of inositol hexanicotinate as a lipid lower agent.

Thank You.

Thanks for your insightful comments.

My experience is based on the experiences of about 10 patients on the no-flush preparation in doses of 1000-4000 mg per day.

If the rationale for the no-flush preparation is that it provides niacin in such a way as to avoid the flush, we should see rises in HDL, reductions in triglycerides, small LDL, and lipoprotein(a), regardless of the type of hyperlipidemia present (IIa, IIb, III, etc.).

After using no-flush for up to one year, I have seen absolutely no effect, accepting my relatively small experience.

Please also understand that my focus is prevention and reversal of coronary heart disease, something that the Track Your Plaque approach does exceptionally well, so I try not to stray off too far from our focus. But why would no-flush have any beneficial effects on arthritis, etc.,as an alternative method of delivering niacin when niacin itself does not possess these effects? I'm not sure I follow the rationale. To be included in a program of coronary atherosclerotic regression, we would have to see substantial effects, as we do with plain old niacin.

Nonetheless, I encourage your continuing interesting thoughts.

Just Friday, a 41-year old woman came to my office for consultation because her doctor didn't know what to do with lipoprotein(a). She had seen a cardiologist who told her to take no-flush niacin. Both the cardiologist and the patient were therefore puzzled when lipoprotein(a) showed no drop and, in fact, was slightly higher on the no-flush preparation.