Amyloid Info

cases of amyloidosis and research results

(2008 Dec blog post)

!Preliminary! I intend to add info as more research is done ... and as I find more (good-quality) info.

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INTRODUCTION :   (a friend with amyloidosis)

In the 2000 to 2005 timeframe, we found out that a family friend, in his fifties, was suffering from a hardening of heart tissue due to an accumulation of 'amyloid' in his tissues. He had been an avid runner, especially fond of marathons, for about 30 years. He discovered the problem because he found it harder and harder to run --- he would get fatigued easily. It turned out that the hardening of his heart tissue was making it hard for his heart to pump blood. This became particularly acute when he tried physical exertion like running.

I had never heard of 'amyloid'. When I did some web searching on it, I found that there are various forms of amyloid, but their composition is generally the same --- a 'glyco-protein'. This is one description. There are many others. The one that is most understandable and meaningful to me is that it is a 'starchy protein' --- or that it is a combination of carbohydrates and proteins. In fact, 'glyco' generally refers to sugar-like compounds, and sugars are a form of carbohydrate.

Since I had had my own run-in with carbohydrates (in particular, sugars --- and starches, which are long chains of sugars), I had done a lot of reading on diets. Hence, I had done a lot of reading on the three main human 'macro-nutrients' --- proteins, carbohydrates, and fats.

In my case, I had been over-indulging in sugars (and starches, which are long chains of sugars that are fairly rapidly broken down into sugars in the digestive tract) for many years. I changed my diet drastically, to include a balance of proteins (nuts, seeds, soybeans, cheese), fibrous carbohydrates (vegetables and fruits), and fats (in mother nature's natural forms, such as olive oil and avocadoes --- not manufactured 'trans-fats', i.e. hydrogenated oils, which are generally blocks of solid fat rather than liquid oils).

A CONJECTURE on amyloid and oil :

When I read that amyloid fibrils are 'glyco-proteins' --- i.e. a combination of carbohydrates and proteins --- it occurred to me that there is no fat in this picture. I wondered if my friend had taken most of the fat out of his diet --- because of his running hobby and because of all the hullabaloo in the 1975 to 2005 time frame over cholesterol and low-fat diets.

    [NOTE: If he had indeed reduced the fat in his diet beyond historically normal levels, in human/paleolithic history, then his condition might, in a sense, be the opposite of what I had experienced. I had too much sugar (a carbohydrate) in my diet. He might have too little healthy fats/oils.]

In other words, I wondered if my friend had relatively high amounts of protein and carbohydrate in his diet and a relatively low amount of healthy fats/oils. And, I wondered if my friend could reverse his condition (or at least mitigate it) by adding healthy fat to his diet --- in moderate amounts, say a couple of salads a day (with oily fruits like olives and avocado --- or with fruit oils like olive oil).

    [It is hard for me to call olives and avocados fruits rather than vegetables, but I have read that they are classified as fruits. Oily fruits? It does not sit right.]

Besides adding some healthy oils or oily fruits to his diet, it may also help to reduce the proportion of starchy carbohydrates in his diet also --- as some of the research cited below suggests. I.e. it would be a diet with starchy carbohydrates (like bread, grains, potatoes, rice) replaced by non-starchy carbohydrates (like broccoli, spinach, carrots, peas, beans).

I very briefly mentioned my speculative solution to a few people --- in nowhere near the detail above or below. The response was cool. So I knew that about all I can do, for now, is occasionally search the literature for information that might support my suspicion that at least some cases of amyloidosis are due to taking too much healthy fat out of one's diet. After all, the billions of cells in one's body have membranes that include a layer of lipids (fats). While it is true that essentially all cells are about 70 to 75% water, it is still the case that a vital component of the cells depends on fatty compounds.

In fact, the needs of our cell membranes are, no doubt, why fat is one of the 3 macronutrients (along with protein and carbohydrates) that are listed in medical books, diet books, and in ingredient lists on food packaging.

I would like to be of help to this friend, but I realized that I would have to collect a lot of good-quality data (whether epidemiological or clinical or laboratory ; whether in humans, in animals, or 'in vitro' ; probably all of the above). If I have a good enough collection of data, then I might be able to convince him that he should at least give that possible solution (healthy levels of fats/oils in his diet) his serious consideration.

Note that there is no known cure, nor even a known cause at this time (circa 2008) for amyloidosis. Several links below confirm this. The treatment approach of U.S. doctors is the ususal --- drugs ('chemotherapy') and surgery --- with no clear solution available.

So, below, I have started collecting information on 'amyloid' and 'amyloidosis'. I intend to periodically add to this information.

THE DATA BELOW :

The first couple of times that I checked for information, many months apart, via web searches, I found that, indeed, there seem to be more studies and observations accumulating on fats/oils, in relation to amyloid, that lend credence to my suggested 'solution' --- or 'mitigator' or 'delayor'.

For example, there are more and more articles appearing that find that a "Mediterranean diet" (one including olive oil and/or fish oils) seems to make amyloidosis less likely. And there are more and more articles appearing that suggest that components of fish oils (or castor oil) are beneficial to treat or avoid or delay amyloidosis.

So I have collected some web links and references below. Since web links often go dead after a year or so, I will usually present a few chosen sentences from the web page or web site that seem to capture the gist of why I listed the link.

Generally, I hope to present sentences that present information in 'everyday language' --- not reams of jaw-breaking chemical and medical names--- and not statistics presented in such detail that they would put anyone to sleep. So here goes.

I have grouped the info-items in several categories, including

If you click on these links (which take you to a section below, on this page), you can click on the Back button of your web browser to return to this list of categories.

DEFINITIONS of amyloidosis (and amyloid) :

From this page at wrongdiagnosis.com somes the following two definitions.

    WARNING: This is a huge page that takes a long time to load. So you may want to simply read the two definitions below. (Why don't people break up pages like this? Wait, I'll answer that. Probably because these pages are being maintained by people who do not understand how to break the page up --- because they are not computer programmers or well-self-educated web programmers. And their supervisors are clueless --- in one way or another.)

  • Amyloidosis : A disease characterized by the accumulation of insoluble amyloid protein in tissues and organs which in turn affects the functioning of these tissues and organs.

  • Amyloidosis AL : A disease involving the abnormal deposit of amyloid fibrils in virtually any part of the body - the heart, liver, kidney and peripheral and autonomic nerves are most commonly affected. The abnormal amyloid fibrils are produced [by] abnormal plasma cells in the bone marrow. In some cases, the excess growth of abnormal plasma cells can result in a cancerous condition called myeloma resulting in bone pain and infections. A patient with myeloma may develop amyloidosis but it is rare for a patient with AL amyloidosis to go on to develop myeloma.


    NOTE:

    Amyloid can be deposited in many kinds of tissues and many organs, not just the heart. This latter definition points out that other sites include bone marrow, kidneys, and nerve sheaths. Amyloid deposits around nerves are suspected of being a main cause of Alzheimer's conditon in old age. And if you do a web search on 'amyloid' or 'amyloidosis', you will find that a large portion of the hits you get have to do with Alzheimer's disease.

    This note on Alzheimer's brings up the fact that amyloidosis is mostly an older person's disease. It rarely affects children, even though there are cases in which certain genetic defects, involved in the synthesis of certain amyloid-related proteins, are known to create a higher likelihood that a person will suffer from 'amyloidosis' as years go by. BUT ... with the worsening diets/foods in the U.S. and the consequent epidemic of obesity and diabetes, it may be the case that amyloidosis strikes more and more younger and younger people.

    In one case of twins with the same genetic defect which facilitated amyloid generation, one twin was affected by amyloidosis 16 years later than the other twin --- reportedly because the more fortunate twin had been taking castor oil almost daily throughout his life. This is one more plus for my healthy oils theory --- which proposes that a historically-normal 'balance' of healthy oils in one's diet would eliminate (or delay) the onset of amyloidosis. Think paleolithic man here --- hunter gatherers --- roots, nuts, seeds, fruits.


Another definition/description :

A discussion of amyloidosis (with definition) is here at Cedars-Sinai Hospital. Some extracts follow.

"Amyloidosis is a condition in which too much of a particular protein (amyloid) collects in the organs, so that they are not able to work normally. Amyloidosis can affect the heart, kidneys, liver, spleen, nervous system, stomach or intestines. The condition is rare (affecting fewer than 3,000 people in the United States each year), but it can be fatal.

Amyloidosis sometimes develops when a person has certain forms of cancer, such as multiple myeloma, Hodgkin's disease or familial Mediterranean fever (an intestinal disorder). It also sometimes occurs in people with kidney disease who have undergone dialysis for a long time.

There are three major forms of amyloidosis:

  • Primary amyloidosis, which is the most common. It occurs without another associated disease and most often affects the heart, lungs, skin, tongue, nerves and intestines.

  • Secondary or acquired amyloidosis, which is associated with chronic diseases, such as tuberculosis, rheumatoid arthritis or osteomyelitis. It most often affects the kidneys, spleen, liver and intestines. If the underlying disease is treated, this form of amyloidosis will go away.

  • Hereditary amyloidosis, which runs in families. This type often affects the nervous and digestive systems."

"Causes and Risk Factors

The cause for amyloid to be produced and to collect in the tissues is not known. ...

The disease starts in the bone marrow. Bone marrow creates red and white blood cells, platelets and antibodies that protect the body against infection. After the antibodies have done their work, the body breaks them down. When the bone marrow cells produce antibodies that cannot be broken down, amyloidosis develops. The antibodies build up in the blood and eventually get deposited in the tissues as amyloid."

    [NOTE: I wonder whether this 'starting in the bone marrow with antibodies that cannot be broken down' is a widely accepted explanation of the development of amyloidosis. I have not seen it mentioned much elsewhere. I.e. is this just a theory at this point? Some citations below indicate that this may describe Amyloidosis AL, but not Amyloidosis AA.]


Another definition/description :

There is more description of what amyloid is here at the UCL (University College London) Centre for Amyloidosis and Acute Phase Proteins. Here is a small extract.

"How is Amyloid made?
Most amyloid-forming proteins are present in the blood, some made in the liver (e.g. in AA amyloidosis) and others made in the bone marrow ( AL amyloidosis). The process of amyloid formation can occur when these proteins are either being produced in excessive quantity (e.g. in AA amyloidosis) or in abnormal forms (e.g. in AL amyloidosis) for one reason or another. The handful of proteins that can form amyloid are able to adopt an abnormal structure that enables them to aggregate in a very stable manner and become lodged in the tissues. It is not known what triggers the initial formation of amyloid but once the process is underway, amyloid tends to build up more quickly than it can be broken down. As a result amyloidosis is usually a progressive disease unless production of the particular amyloid forming protein can be reduced by treatment of the underlying disorder."

Another definition/description source :

There is more description/definition of amyloidosis at this Wikipedia page on Cardiac Amyloidosis. There are links to more amyloidosis pages on this page.

The Wikipedia Amyloidosis page even has links to people (politicians, authors, sports figures) who have had amyloidosis, and links to clinics.


Another definition/description :

Here is a page on Congestive Heart Failure at PreventDisease.com that uses the "starchy protein" description of amyloid.

"Amyloidosis, a disease in which a starchy protein (amyloid) builds up in tissues and organs, can lead to congestive heart failure."


Another info source :

There is more description/definition of amyloidosis here at a blog at mentoring-uk.org.uk, under the title "Amyloidosis Explained" (2008 Apr).

"The most common type of amyloidosis is known as Primary Systemic Amyloidosis, and it affects the bone marrow. It is a result of mutations in certain proteins that play such vital roles as clotting the blood (fibrinogen), naturally killing bacteria (lysozyme), and transporting cholesterol to the body's tissues (Apo-lipoprotein B). This type of amyloidosis can affect the entire body at once, causing various organs to shut down or fail.

There are types of the disease that affect the liver, and those types are believed to be genetic. Genetically linked types of the disease are known as Familial Amyloidosis. These types of the disease are thought to be caused by a mutation of the transthyretin protein, which is a carrier of Vitamin A in the body. Genetically linked forms of amyloidosis have a high chance of being passed down through offspring. The disease can also be as a result of long-term dialysis in people with kidney disease."


Another info source :

There is more description and definition of amyloidosis here at
autoimmunedisease.suite101.com (2007 Aug). Here is an extract.

"While the condition known as amyloidosis has been reported for more than 300 years, itís only been in the last 20 years that researchers discovered the protein abnormalities that characterize amyloidosis."

Another info source :

There is more description/definition of amyloidosis here at txai.org.

Here amyloid is called "sticky protein" and called poorly water-soluble.

There is also a discussion of the fats/oils in cell membranes here. The discussion points out that there are 'lipid rafts' of various types of fats in the membranes. The differences in fat/lipid types are somewhat similar to the differences between butter (near solid) and olive oil (liquid).


HUMAN RESEARCH ARTICLES :

A study which suggests beneficial effects on one type of amyloid via a low-carbohydrate diet is reported here at a 'PubMed' site, which is a service of the U.S. Libary of Medicine and the National Institutes of Health.

TITLE:
Diet-induced weight loss is associated with decreases in plasma serum Amyloid A and C-reactive protein ... in obese subjects.

AUTHORS:
O'Brien KD, Brehm BJ, Seeley RJ, Bean J, Wener MH, Daniels S, D'Alessio DA.

Department of Medicine, Division of Cardiology, Box 356422, University of Washington, 1959 Northeast Pacific Street, Seattle, Washington 98195-6422, USA. cardiac@u.washington.edu

J Clin Endocrinol Metab. 2005 Apr;90(4):2244-9

QUOTE from summary:
"SAA [Serum Amyloid A] ... levels were measured ... on baseline and 3-month plasma samples from 41 obese women completing a randomized trial comparing a low-fat diet (n = 19) and a very low-carbohydrate diet (n = 22). ... The very low-carbohydrate dieters had a significantly greater decrease in [Serum Amyloid A] ... their weight loss also was significantly greater."

The better weight loss via low-carbohydrate diet, versus a low-fat diet, was bolstered by these authors with more data reported here, another 'PubMed' page.

ANIMAL RESEARCH ARTICLES :


First animal research article :

From this page at health.dailynewscentral.com (2005 Oct) comes the headline "High Fat, Low Carb Diet May Curb Alzheimer's Disease".

Some quotes extracted from this article :

"A high-fat, low-carbohydrate diet improved the condition of mice with the mouse model of Alzheimer's disease, according to a study published in Nutrition and Metabolism.

The brain protein amyloid-beta, which is an indicator of Alzheimer's, was reduced in mice ...

Samuel Henderson of Colorado-based pharmaceutical company Accera and colleagues in Belgium made the findings, which contradict previous studies suggesting a negative effect of fat on Alzheimer's disease."


In case you cannot get to the Nutrition and Metabolism article in the link above, here is the title and authors of the article, followed by a quote.

TITLE:
A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer's disease

AUTHORS:
Ingrid Van der Auwera, Stefaan Wera, Fred Van Leuven, and Samuel T Henderson (corresponding author)

SUMMARY QUOTES:
"Alzheimer's disease (AD) is a progressive neurodegenerative disorder that primarily strikes the elderly. Studies in both humans and animal models have linked the consumption of cholesterol and saturated fats with amyloid-beta deposition and development of AD. Yet, these studies did not examine high fat diets in combination with reduced carbohydrate intake. Here we tested the effect of a high saturated fat/low carbohydrate diet on a transgenic mouse model of AD.

......

Here we demonstrate that a diet rich in saturated fats and low in carbohydrates can actually reduce levels of amyloid-beta."

Another animal research article :

Some results with fish oil in mice are reported here at Bio-Medicine.org (2005 Mar), under the title "Fish oil holds promise in Alzheimer's fight". Following are a few quotes from the Bio-Medicine Biology News article.

"Researchers with the Department of Veterans Affairs (VA) and the University of California at Los Angeles (UCLA) found that a diet high in docosahexenoic acid, or DHA -- an omega-3 fatty acid found in relatively high concentrations in cold-water fish -- dramatically slowed the progression of Alzheimer's disease in mice. Specifically, DHA cut the harmful brain plaques that mark the disease. The results appear in the March 23 online edition of the Journal of Neuroscience.

Senior author Greg M. Cole, Ph.D., a neuroscientist at the Greater Los Angeles VA Healthcare System and UCLA, says 'The good news from this study is that we can buy the therapy at a supermarket'. "

"The new study involved older mice genetically altered to develop Alzheimer's disease. The researchers fed one group of the mice DHA-fortified chow. The control mice ate a normal or DHA-depleted diet.

After three to five months --- the equivalent of several years in human biology --- the high-DHA group had 70-percent less buildup of amyloid protein in the brain. This sticky protein makes up the plaques, or patches, that are a hallmark of Alzheimer's."


Another animal research article :

An article in the Journal of Immunology (1987) also indicated, in mice, that fish oil reduces levels of a type of amyloid.

TITLE:
A fish oil diet inhibits amyloid P component (AP) acute phase responses in arthritis susceptible mice

AUTHORS:
ES Cathcart, RF Mortensen, CA Leslie, JM Conte and WA Gonnerman

PUBLICATION:
Journal of Immunology, Vol 139, Issue 1 89-91,1987

A brief QUOTE:
"AP [Amyloid P] was measured ... in plasma taken 5 wk and 15 wk ... AP levels were less in fish oil fed males and females."

Another animal research article :

This page at the RDS (Research Defence Society) in the U.K. provides another paper that claims fish oil has a beneficial effect on amyloid in mice. See reference 23 of the 36 on this web page.

Based on reference 23, this page says:
"Aged, genetically engineered mice predisposed to Alzheimer's disease that were fed the fish oil DHA (docosahexaenoic acid), an omega-3 fatty acid, developed significantly less amyloid protein."


HUMAN CLINICAL CASES :


A human clinical reference :

From this page at uscap.org (U.S. and Canadian Academy of Pathology) comes a description of a 37 year old woman suffering from fatigue and a somewhat enlarged heart ("mild cardiac enlargement"). A heart biopsy indicated amyloidosis as the cause.

She was treated via chemotherapy, although the outcome does not seem to be mentioned.

Some quotes I found of interest :

"Over 20 distinct types of amyloid deposits are known to occur based on the specific amyloidogenic protein present."

The 12 references cited included

    "An 80-Year-Old Man with Shortness of Breath, Edema, and Proteinuria."
    N Eng J Med 2005; 352:2111-2119.

Another human clinical reference :

There are amyloidosis case histories here at amyloidosis.org. There is also a questions and answers section at this site.

Here is a lead-in quote from the Case Histories page.

"This is a chronicle of experiences from one patient with renal involvement, some of which may be common to everyone and some of which will not be. As you will see, he came through the chemotherapy at the hospital pretty easily in comparison to others and his recovery time was quite short. However, as you will also see, the chemotherapy didnít cure him so the chronicle will also deal with my reaction to the second part of the protocol; a thalidomide/dexamethasone regimen. Hereís the story which began in the summer of 2004 and his first edition in March, 2005 with additions to come. The chronicle includes details on the evaluation at Memorial Sloan-Kettering, some things for caregivers, diet, the treatment process, and recovery. You can check for updates at www.utc.edu/Faculty/Daniel-Baker/amyloidosis/."


Another (possible) human clinical reference :

At this page of an Austin Texas news-media station (2005 Jul) a registered dietician named Tavis Piattoly is quoted as saying ...

"Fish oil supplements decrease brain plaque by 40 percent and also decrease something called an amyloid protein by 70 percent." It would take further searching to confirm whether he was basing this statement on human or animal results --- and to ascertain the source of that statement. I simply include this quote and his name here to facilitate further searching, if deemed useful. (The 70 percent figure may come from the work of Cole at UCLA, in mice, which was cited above.)

'IN VITRO' RESEARCH :


An 'in vitro' reference :

Beneficial effects of fish oil on rat neurons and human neurons were reported here here at scienceblog.com. "The researchers examined the effects of fish oil, or its component DHA, in multiple biological systems and administered the oil or fatty acid by diet and by adding it directly to neurons grown in the laboratory."

"DHA found in fish oil increases the production of LR11, a protein that is found at reduced levels in Alzheimer's patients and which is known to destroy the protein that forms the 'plaques' associated with the disease."

And a reader response at this blog is quoted here:
"If it's DHA that's the big to-do, far more sustainable sources than fish abound: a couple of tablespoons a day of flaxseed or flaxseed oil or mixed nuts and seeds provide the daily recommended dose. As the omega-3 fatty acid isn't damaged by baking for up to 2 hours at temperatures of up to 350F/180C, they can be added to cakes, cookies, and breads; they can be added to oatmeal; and the oil can be drizzled on salads, into soups after cooking, over toasted bread before adding bruschetta, etc. It's extremely easy to do. With Alzheimer's in the family, I'm very pleased that something I already do daily can make such a difference."

INTERESTING MISCELLANEA :


A miscellaneous amyloid reference :

The following is quoted here. This quote seemingly was found in an article in the journal 'Nature' ...

    Grave Solutions, by Daedalus. Nature, Vol 381, 9 May 1996.

"Mad cow disease is still headline news. A molecule of the cow's brain protein gets wrongly folded into a 'prion'. This somehow persuades other protein molecules to fold the wrong way too. Prionic protein spreads relentlessly through the creature's brain.

Brains seem strangely vulnerable to mal-folding proteins. Even Alzheimer's disease seems to develop by the spreading of amyloid plaques of knotted protein. What we need, says Daedalus, is some sort of 'molecular penetrating oil' that will insinuate itself into protein molecules and force them to unwind."

This rather simply conceived (1996) conjecture may actually prove to be a good basic description of an eventual solution for amyloidosis ... for one or more of its forms.


Another miscellaneous amyloid reference :

There are even cases of amyloid in the eye as noted here, at the Archives of Optholmology.

TITLE:
Isolated Vitreoretinal Amyloidosis in the Absence of Transthyretin Mutations

PUBLICATION:
Arch Ophthalmol. Jan 2004 ; 122: 123-125.

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Posted 2008 Dec 18.
Changed slightly, to improve printing, 2009 Aug 22.
Changed page format slightly 2013 Apr 28.