Long Term Mood Improvement using NAC in Autism

A more recent post on this subject is here:

http://epiphanyasd.blogspot.com/2014/08/nac-for-long-term-use-in-autism.html

NAC (N-Acetyl Cysteine) is an anti-oxidant that is part of the autism therapy I have implemented.  I have now received feedback from other parents who are also surprised by the positive effect it has on their child with autism.  So far, it has had a positive impact in 100% of cases.

In the literature, there are several schools of thought as to why NAC is effective. 

1. As a free radical scavenger in its own right
2. As a precursor to Glutathione (GSH)
3. As a glutamate antagonist
4. Reducing homocysteine

Glutamate is one of the brain's two most important neurotransmitters, the other being GABA.  Glutamate is excitatory and so too much of it would cause you a problem.  NAC can act as an antagonist to glumate.  This is all very nicely explained by Emily Deans, a psychiatrist in Massachusetts who has a very interesting blog of her own.

• Glutathione: We Loves It (NAC and Autism)

In my research into the autism comorbidity asthma, I also came across plenty of talk about oxidative stress and anti-oxidants.  NAC is used, but it seems like they are looking for something stronger.

The main impact is as a precursor to Glutathione (GSH)

I recently learnt that in autism (or at least the one my son is affected by) the reason is without doubt number two.  The other roles (scavenger/antagonist) are irrelevant.

The reason I know this, is that after a few months NAC effectively stopped working.  This coincided with an asthma flare-up.  Now, I initially thought that the asthma attacks had released inflammatory cytokines and that these had stimulated the ever-present neuro-inflammation in the brain.

This is highly plausible and indeed I have literature showing which cytokines are released by asthma attacks.  So I thought that by firmly dealing with the asthma, I would at the same time subdue the autism.  This did not happen.

So after a few days I came up with "plan B", which did prove to be successful.  I hypothesised that the NAC had stopped working because I was not giving enough vitamin B12, which is part of the chemical process in which GSH is synthesised from NAC.  I have no means of knowing how much is needed exactly. In related processes both vitamin B6 and B9 are also involved.

I increased the B vitamins and within hours things began to revert towards the previous behavioural equilibrium.

So it was most likely the failure of NAC to produce GSH, and thus reduce oxidative stress, that had sparked the asthma flare-up. (this is will be covered on my later post of asthma as a comorbidity in autism)

But how much B12 is needed to synthesise GSH?

In your diet you have vitamins B6, B9 and B12, but it is unclear how much is needed to synthesise GSH.  A further complication is that B vitamins are not well absorbed in the gut, and some people absorb them better than others.  Older people are known to absorb B12 poorly.  There are expensive sub lingual B vitamin supplements, but there is no evidence that they actually work better.

There are at least two NAC products targeted at older people to protect them from memory loss and Alzheimer's disease:-

• Betrinac   
• Cerefolin NAC

 Both products combine NAC with vitamins B6, B9 and B12,

                                             Over the counter NAC        Cerefolin NAC        Betrinac


N-acetylcysteine (NAC)              600mg                            600mg                     600mg
Vitamin B9 (folate)                                                          1,000 mcg               800 mcg
Vitamin B6                                                                           25mg                       20mg
Vitamin B12                                                                    1,000mcg                1,000mcg



 Both products are for preventing memory loss, rather than just increasing GSH.


For a comprehensive look into B vitamins including their role in the brain, and how they are (or are not) absorbed, take a look at this link from the US Office of Dietary Supplements.


Reducing homocysteine

Homocysteine is linked with strokes, and particularly in the US there are doctors who use NAC for the purpose of lowering homocysteine.

Dr. Baum, medical director of the Mind/Body Medical Institute, a Harvard affiliate, recommends 1,000 micrograms (mcg) of folate, plus 25 milligrams (mg) of vitamin B6, 1,000 mcg of B12, and 1,800 mg of the amino acid N-acetyl-cysteine (NAC). "With folate, B6, B12, and NAC supplements, almost everyone will have normal homocysteine levels," says Dr. Baum.

There is even a discussion about the role of homocysteine in autism.  A very recent paper from Poland is: A focus on homocysteine in autism

I think think that high homocysteine, just like low GSH, is a marker of oxidative stress.  In some of the literature it is stated that homocysteine cause oxidative stress.

Here is another paper: Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism

 

And yet another one:-

Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders

 

If you read all the papers you will come across various graphics showing biological cycles within the body, like the one below.  This is how I know that the various B vitamins are needed.

Vitamin B12 Therapy

I really just need to know how much B12 is needed and how to give it.  In the end the best resource turned out to be a  bulletin from a US medical insurer, and here it is:-

Clinical Policy Bulletin:  Vitamin B-12 Therapy

The document is very thorough; here are some key parts:-


Background

Vitamin B-12 belongs to the family of cobalamins. It is available in all animal-derived foods, and is absorbed at a rate of 5 mcg per day. After being ingested, vitamin B-12 becomes bound to intrinsic factor, a protein secreted by gastric parietal cells. The vitamin B-12/intrinsic factor complex is absorbed in the terminal ileum by cells with specific receptors for the complex. The absorbed complex is then transported via plasma and stored in the liver. Since the liver stores 2,000 to 5,000 mcg vitamin B-12 (adequate for up to 5 years), dietary deficiency of cobalamin (Cbl) is rare. In most cases, vitamin B-12 deficiency is due to an inability of the intestine to absorb the vitamin, which may result from an autoimmune disease that reduces the production or blocks the action of intrinsic factor, or from other diseases that result in intestinal malabsorption. The most frequent underlying cause of vitamin B-12 deficiency is pernicious anemia, which is associated with decreased production of intrinsic factor.


In a systematic review of randomized trials on vitamin B-6, B-12, and folic acid supplementation and cognitive function, Balk and colleagues (2007) stated that despite their important role in cognitive function, the value of B vitamin supplementation is unknown. A total of 14 trials met selection criteria; most were of low quality and limited applicability. Approximately 50 different cognitive function tests were assessed. Three trials of vitamin B-6 and 6 of vitamin B-12 found no effect overall in a variety of doses, routes of administration, and populations. One of 3 trials of folic acid found a benefit in cognitive function in people with cognitive impairment and low baseline serum folate levels. Six trials of combinations of the B vitamins all concluded that the interventions had no effect on cognitive function. Among 3 trials, those in the placebo arm had greater improvements in a small number of cognitive tests than participants receiving either folic acid or combination B-vitamin supplements. The evidence was limited by a sparsity of studies, small sample size, heterogeneity in outcomes, and a lack of studies that evaluated symptoms or clinical outcomes. The authors concluded that there is insufficient evidence of an effect of vitamin B-6, B-12, or folic acid supplementation, alone or in combination, on cognitive function testing in people with either normal or impaired cognitive function. This is in agreement with Clarke et al (2007) who stated that randomized trials are needed to ascertain the relevance of vitamin B-12 supplementation for the prevention of dementia.

Vitamin B-12 therapy can be administered orally or by injection. Vitamin B12 tablets of up to 5,000 mcg may be obtained over the counter without a prescription.

In a review on vitamin B-12 deficiency, Oh and Brown (2003) noted that, because most clinicians are generally unaware that oral vitamin B-12 therapy is effective, the traditional treatment for B-12 deficiency has been intramuscular injections. The authors cited evidence that demonstrates, however, that oral vitamin B-12 has been shown to have an efficacy equal to that of injections in the treatment of pernicious anemia and other B-12 deficiency states (Elia, 1998; Lederle, 1998; Kuzminski et al, 1998; Lederle, 1991). The authors explained that, although the majority of dietary vitamin B-12 is absorbed in the terminal ileum through a complex with intrinsic factor, there is mounting evidence that approximately 1 % of a large dose of oral vitamin B-12 is absorbed by simple diffusion which is independent of intrinsic factor or even an intact terminal ileum.
Kuzminzki et al (1998) reported on the outcome of 33 patients with vitamin B-12 deficiency who were randomized to receive oral or parenteral vitamin B-12 therapy. Patients in the parenteral therapy group received 1,000 mcg of vitamin B-12 intramuscularly on days 1, 3, 7, 10, 14, 21, 30, 60, and 90, while those in the oral treatment group received 2,000 mcg daily for 120 days. At the end of 120 days, patients who received oral therapy had significantly higher serum vitamin B-12 levels and lower methylmalonic acid levels than those in the parenteral therapy group.

 On treating B12 deficiency :-

Although the daily requirement of vitamin B-12 is approximately 2 mcg, the initial oral replacement dosage consists of a single daily dose of 1,000 to 2,000 mcg (Lederle, 1991; Oh and Brown, 2003). This high dose is required because of the variable absorption of oral vitamin B-12 in doses of 500 mcg or less. This regimen has been shown to be safe, cost-effective, and well tolerated by patients.


CONCLUSION


Long term high dose NAC will require careful supplementation with B vitamins.   If NAC is using up vitamin B12 faster than your child is absorbing it from food and supplements, B12 will be used up from the liver and other vitamin stores in the body.  These stores will eventually be depleted and vitamin B12 deficiency will result, if you continue to give NAC.  This is best avoided.

If money is of no concern, best to buy Cerefolin NAC or Betrinac.  If on a budget, then use the cheap NAC available on-line or in your pharmacy; but be careful to supplement far higher amounts of B6, B9 and B12 than the RDA (recommended daily amount).

Cerefolin NAC and  Betrinac have 400 times the RDA of B12, 4 times the RDA of B9 and 15 times of B6.  But each of these tablets only has 600mg of NAC.  In the autism trials the dose of NAC is 4 times higher.

It is evident that B12 is the key vitamin that acts as a precursor with NAC to form GSH (Glutathione), so this is the one to keep a close eye on should your child's NAC appear "to stop working".

It looks like 1,000 mcg of B12, of which 1% may be absorbed, is a fair place to start.  Such supplements are relatively inexpensive, and widely available.



 

Angelina Jolie or Destiny’s Child?

At the time of writing this post Angelina Jolie’s aunt has succumbed to the same cancer that killed Angelina’s mother and she announced that she also carried the same defective gene.  She opted to take pre-emptive action and, in effect, cheat a nasty early death from breast or ovarian cancer.

I have read so much research into autism, that it is pretty clear to me, that you could calculate an Autism Risk Factor (ARF) for prospective parents, if you really wanted to.  Would you really want to?  I expect those with direct experience of autism might be in favour, the others probably would not even bother to answer the question.  Since few truly autistic people have children, it is really more of a question for their siblings; do they want Destiny’s Child?

It may sound depressing, or something to do with eugenics, but actually it does not have to be.  I am not suggesting the sort of genetic and chromosome testing that is already routinely done for conditions like Down’s syndrome.  I am talking about the kind of lifestyle changes that ideally a woman who smokes, drinks heavily or takes drugs, should take when she wants to have a child.

If your ARF puts you at risk, then you would receive a list of lifestyle changes, you should take to minimize the risk to your future child.

 

Autism Risk Factor (ARF)

I am not qualified to develop the ARF, but I am confident enough to highlight two of the factors that should go into it:

 

1.     Maternal & paternal family history of autoimmune diseases

Auto-immune diseases including, but not limited to, history of type 1 diabetes, rheumatoid arthritis, celiac disease and hypothyroidism.  Here is some supporting evidence, for those who are interested:-

·         Association of Family History of Autoimmune Diseases and Autism Spectrum Disorders

 

·         Familial Clustering of Autoimmune Disorders and Evaluation of Medical Risk Factors in Autism

 

2.     Maternal & paternal stress capacity

This risk factor is my invention.  I used to only really think about mechanical stress, but now I know all about physiological stress, psychological stress and that big one, oxidative stress.  It seems, remarkably to me, that the latter three types of stress are in fact one and the same.

Put another way, physiological stress, psychological stress and oxidative stress are reflections of each other.  If you have got one, you will have all three.

The good news is that can use obvious visible cues to spot people will a low stress capacity and you could even then confirm it with a laboratory test of their oxidative stress (GSH redox level).

I recently took four short airplane flights and I observed people with chronic nail chewing (male) and obsessive nail filing (female) sitting beside or in front of me; it looks like about 5% of the flying population.  If you added the non-autistic people with mild stereotypy (stimming) like foot flapping, and those with Trichotillomania (compulsive hair pulling, that we learned about in the posts on GSH/NAC) you would have a large proportion of those people living in some degree of potentially damaging oxidative stress.

I think the maternal stress capacity would be most relevant, but the fetus’s own stress capacity is also important, and some of that clearly comes from the paternal side.

Conclusion

So the conclusion for Ted, aged 12, is to grow up and find a nice calm girlfriend and buy a large supply of NAC, just in case.

 

 

 

The Swedish Disease

Ted, (aged 12, and supposedly “normal”) and his brother Monty (aged 9, and now steadily becoming more “normal”, as this blog progresses) go to the same school as a Swedish family.  In Ted’s class is a Swedish girl, Charlotte, and her younger brother is in the Primary school along with Monty.  I have been both surprised and impressed, by how nice the kids in Primary are to kids with any kind of special need.  However, once they make the big leap to Secondary, they stop being so nice; it becomes cool to be critical and even cruel.

Ted’s Swedish friend, Charlotte, was explaining to their class that her younger brother had something called Attention Deficit Hyperactivity Disorder, but it was OK, because he only had 10% ADHD.  Ted of course then replied “and you have got the other 90%”.  Some of the other things they get up to are far, far worse; one reason why I put Monty down a couple of years in Primary.

But, the Swedish Disease is not ADHD.

During my research, I recently came across some references to so-called “Somali autism clusters”; this caught my attention and so I decided to delve deeper.

It seems that following the descent of Somalia into becoming a failed state, many refugees have been welcomed by the United States and Sweden, in particular.  In the US there are now communities living in Minneapolis and San Diego.  Not long had they arrived in their new homeland, when they started to produce large numbers of autistic children; sounds odd does it not?

Swedish researchers got on the plane to Minneapolis in the US, to launch a joint investigation and it was reported that Dr Wakefield wanted to go to San Diego to investigate.  The Swedes did not come up with an explanation that convinces me.  I think I have a much better one, and one that Dr Paul Ashwood, from the University of California might agree with.

The Swedish Somalis said they had never encountered autism before and so they named it the “Swedish Disease”.  The Swedish researchers concluded that since both Sweden and Minneapolis are far north, where the sun does not shine so much, the autism was the result of a lack of vitamin D.  That sounded odd to me; what about the cluster in San Diego that Dr Wakefield wanted to get in touch with?  Last time I was in California, the sun hardly ever went away.

A much more likely explanation is related to the immune system.  I have never had the pleasure of touching down in Mogadishu (the capital of Somalia, in case you did not know) but I did travel extensively in some poorer parts of Asia.  The level of hygiene and cleanliness in rural parts of India would really shock most westerners; the most effective strategy is just not to eat anything.  I came back 9 pounds lighter.

In my recent posts, I showed how the immune system plays a major role in the predisposition of children to autism; to me it is hardly surprising that first generation Somali children, born in ultra-clean Sweden and America, have a high incidence of disease related to the immune system, and to neuroinflammation in particular.  I dare say they never had much asthma in Somalia either.

The parents’ immune system has been toughened by all manner of parasites, bacteria and virus and has no doubt evolved to be prepared for it.  The children inherited their parents’ immune system, but it has stopped being challenged by any kind of serious attack.  Then in utero, or in very early childhood, a big oxidative shock came along and the immune system went crazy and over-reacted (a cytokine storm); massive neuroinflammation caused permanent brain damage and autism was the result.

It’s just my theory, but if you ever read that Somali immigrants are complaining about asthma and food intolerance, it might just be right.

More recently, the Swedes did a very large study looking at autism in all their immigrant population, here is an interesting link discussing the study:- 

Swedish study dissects autism risk in immigrants

 

Peter Hypothesis Regarding the Cause of Autism

Peter Hypothesis Regarding the Cause of Autism,

 The Predisposition of some Children towards it and Implications for Treatment

Autism is a spectrum of behaviours and disorders that result from damage and subsequent malformation of the developing cerebellum.  The damage in classic autism occurs in utero, whereas in the case of regressive autism, there is a second oxidative shock that occurs around a key point in brain development, triggering the onset of autism.  The cause of the cerebral damage is an oxidative shock from one or more of a variety of possibilities, not limited to, maternal stress and infection during pregnancy and toxins such as mercury crossing the blood brain barrier (BBB).  Individuals with autism, and many of their close relatives, have a predisposition to the condition, due to an inherited over-reactive immune system.

The immune system may have become over-reactive to infection partly due to a lack of the on-going attacks, for which it has evolved.  This may be another case for the well documented “Hygiene Hypothesis”, in which a little bit of dirt, rather than an apple a day, keeps the doctor away.

The result is that while in modern society the likelihood of an oxidative shock has increased, the immune system has become so relaxed, due to a sterile environment, that it becomes over-activated when confronted by a severe oxidative shock.  A cytokine storm then rages and the resulting severe neuroinflammation and oxidative damage causes permanent brain damage.  The brain tries to repair itself, but as it continues to grow, it deforms.  A milder neuroinflammation typically continues throughout life and this aggravates the observed autistic behaviours.

In very rare individuals with mild autism, a “recovery” can be observed.  This is most likely the result of successful behavioural therapy of some kind and the on-going neuroinflammation subsiding, for reasons unknown.    In cases where brain damage is substantial, as is generally reported to be the case in classic autism, “recovery” is somewhat fanciful; optimal outcome is the realistic goal of therapy.

A secondary inherited/genetic factor may eventually be proved to be the permeability of the BBB (blood brain barrier).  This would play a role in both the initial oxidative shock reaching the cerebellum and in the following cytokine storm.  Cytokine molecules are particularly large and those released from outside the brain should struggle to enter it.

Vaccination damage is just one of many possible causes of oxidative shock that could trigger regressive autism; it cannot be the cause of classic early onset autism.  Milder cases of autism, and indeed ADHD, are caused by milder cerebral damage and milder on-going neuroinflammation.

Implications of the Hypothesis

1.       At risk mothers should avoid possible oxidative attack

The overactive immune system is measurable (the simplest and cheapest test is the C-reactive protein test; but cytokine testing would be conclusive) and this knowledge could be used to reduce further cases of autism, by identifying at risk mothers.  The threat of oxidative damage could be reduced by de-sensitizing the immune system during pregnancy (risky, but possible), or perhaps better, by meticulously avoiding oxidative damage during pregnancy, in those in the high risk group.  Most likely, the lack of a “successful” oxidative attack during pregnancy would reduce the likelihood of a secondary shock later on that could tip the balance towards regressive autism.

2.       Reset the immune system

Increased exposure to pets, mild intestinal parasites and dirt in general, would reverse the modern trend towards an unprepared and then over-reactive immune system.

This would have the secondary benefit of reducing the prevalence of a wide range of 21^st century conditions including asthma, food allergies, eczema and even gastrointestinal sensitivity and arthritis.  These are all linked to neuroinflammation and/or an overactive immune system.

3.       Therapy & Treatment

Once the brain damage has occurred we are left with the challenge of how best to manage it and achieve “optimal outcome”.  Now that we have a plausible hypothesis, this will greatly help us (me) finding effective therapies, some of which will be novel.

Therapy needs to take advantage of neuroplasticity, particularly in the very early years, to maximize the potential of the damaged brain.  Intensive early behavioural intervention has been proved to be effective and neurological explanation is that the brain’s own plasticity is being exploited to develop new pathways within it.  In other words, start an ABA programme.

Targets for pharmacological intervention:- 

•     Reduce the on-going neuroinflammation / oxidative stress   

•    Treat secondary issues arising from the malformation of the brain

            ·         Ion channel and neurotransmitter (GABA, glutamate etc.)  malfunction

            ·         Hippocampus malfunction, leading to a cascade of hormone errors (CRH, 
                      TRH, AVP, Oxytocin, Cortisol etc.)

Finished switching ears off!

I had another surprise a couple of days ago; I was standing with Monty outside the entrance to a very noisy ice-cream bar.  There were babies crying, a lady begging rather aggressively and an orderly queue to enter the shop.  Finally, the noise abated and I heard Monty say:-

“Finished switching ears off!”

Is there more to this than the emergence of spontaneous and appropriate speech?

Selective Hearing, Elective hearing and (S)elective mutism

I once did a course called Noise Control as part of my Engineering degree.  I recall that at the start of the course, the Professor confessed his desire to be able to turn his hearing on and off; clearly there were some noises he would prefer not to hear.

If you have children you will have discovered “selective hearing”; whenever you want them to come for a meal, they just do not seem to hear you.  If you offer ice cream though, they will hear the first time you call.

There is also the relatively common case of selective mutism, in people with anxiety disorders, they lose the ability to speak in stressful situations.

I think that many non-verbal autistic children probably have elective mutism; they just decide not to speak, or perhaps there is a barrier inside them that they just cannot get over.

Many people with autistic children initially go through a phase of thinking their child is deaf.  I know a child who lost his hearing and then a couple of years later regained it.  I met him just after his hearing was restored and I was convinced he had autism; he had all the characteristics.

Maybe some autistic children have elective deafness and/or elective mutism and perhaps a little pharmacological intervention could actually help them overcome this barrier?

For Monty, thankfully, these problems are in the past.  For him ABA and PECS did the job.

 

 

 

By Jupiter! - Satins Part 3

Makes more sense if you have read:-
Statins Part 1
Statins Part 2

 

For most of you Jupiter is the fifth planet from the Sun, or maybe the largest planet in the Solar System.  To a young boy like Monty, Jupiter is a red fire engine, normally driven by Fireman Sam.

If you are a cardiologist you will have heard of the JUPITER trial. (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin trial)

It was a huge study looking into the possible benefits of giving statins to older people with low cholesterol.  All the 17,802 subjects had elevated levels of high-sensitivity C-reactive protein (CRP) levels, which is a marker for cardiac (and neuro) inflammation.  Half were given 20mg of a statin and the other half had a placebo.  The study measured their cholesterol, CRP levels and whether they later had a cardiac incident.  The group with the statin lowered their already okay LDL and triglycerides level and also lowered their CRP level by a thumping 37%.

At the time of study termination (median follow up, 1.9 years; maximal follow-up, 5.0 years), 142 first major cardiovascular events had occurred in the statin group, as compared with 251 in the placebo group.

This was interpreted by the authors as evidence that even older people without elevated cholesterol could benefit from statins to reduce their risk of cardiovascular events.

 

 

JUPITER and autism

What JUPITER tells me is that statins were highly effective at reducing inflammation as measured by CRP.

 

Autism and CRP

Now we just need some data on the level of CRP in Autism.  Thanks to those nice people in Iran we have a study called: - The complementary role of high sensitivity C-reactive protein in the diagnosis and severity assessment of autism.

 They concluded:-

► Inflammatory process can play key role in the pathophysiology of autism.
► Higher levels of hs-CRP are detected in autistic children.

► A correlation exists between hs-CRP level and autism severity.

► Hs-CRP can be considered a complementary diagnostic test for autism.
►These findings affirm the role of inflammation in autism.

I guess because Iran is public enemy number two, nobody took much note of this study, except Paul Whiteley of course.

 
 

Autism & Statins

So it looks pretty likely that statins will reduce CRP in autistic subjects and if statins can do this, they will reduce both the neuroinflammation and, by inference, the severity of autistic behaviours.

 

Peter Research

While in the Astra Zeneca-funded JUPITER study there were 17,802 subjects and five years of research; here in the Peter Research Institute we have one subject and one week of research.

As with my Bumetanide research, I am shocked by the almost immediate effect of the drug.  In terms of lowering cholesterol, statins are supposed to take two weeks to reach full effect.  In terms of reducing neuroinflammation the effect appears to be much faster – very encouraging but, to be honest, quite unexpected.  

Back to Cholesterol & Autism

The important thing is that statins appear to reduce autistic behaviours, at least in my subject; it would however also be nice to fully understand why.  The research shows the presence of dyslipidemia (abnormal amounts of lipids) in boys with autism.

 

Alterations in lipid profile of autistic boys: a case control study

The findings were: - LDL normal, HDL low, Triglycerides high, Total cholesterol normal.  The current benchmark used is that Total Cholesterol divided by HDL should be less than 4.5.  With low HDL and high triglycerides, this could put many autistic subjects in the zone of elevated risk.

Also, be aware of the very rare condition called Smith-Lemli-Opitz Syndrome (SLOS), caused by low levels of cholesterol;  it is explained in this open-access paper:-

Abnormalities of Cholesterol Metabolism in Autism Spectrum Disorders

In one of the studies I read that CRP always drops before the fall in cholesterol.  This would imply that in the case of ASD, the cholesterol issue is just a consequence; it is the precursors that actually matter.  At least to me, that makes a lot of sense.



In case you missed the prequels:

Statins Part 1
Statins Part 2


and now there is Part 4  http://epiphanyasd.blogspot.com/2013/05/tapas-time-statins-part-4.html