Hello, Elizabeth. Thank you for asking questions about how to best address amyloidosis.
I personally have not seen, nor treated any cases of amyloidosis, but I will be able to provide information regarding the condition. Hopefully by understanding the disease, one can make more logical suggestions regarding nutritional interventions.
Well done thus far looking into any evidence that may exist for nutritional interventions.
Amyloidosis is a generic term that refers to the extracellular tissue deposition of fibrils composed of low molecular weight subunits (most of which are in the molecular weight range of 5 to 25 kD) of a variety of proteins, many of which circulate as constituents of plasma. At least 30 different human and 10 different animal protein precursors of amyloid fibrils are now known, and the corresponding amyloid diseases associated with each of the affected molecules and nomenclature for subunit proteins have been described.
• Sipe JD, et al. Amyloid fibril protein nomenclature: 2012 recommendations from the Nomenclature Committee of the International Society of Amyloidosis. Amyloid. 2012 Dec;19(4):167-70. Epub 2012 Nov 1. (http://tinyurl.com/lg6veum).
Amyloidosis is a rare and potentially fatal disease that occurs when amyloid proteins build up in the body’s tissues and organs. The abnormal protein is produced by cells in the bone marrow. It affects different organs in different individuals. However, it usually occurs in the heart, kidneys, liver, spleen, nervous system and gastrointestinal tract. Other areas of involvement include the musculoskeletal system, respiratory system, haematologic system and the skin.
There are several different types of amyloidosis. The disease is classified based on where the protein is produced. The most common type of the disease, primary systemic amyloidosis, is a bone marrow disorder. Other types, which originate in the liver, are considered to be familial or inherited. Amyloidosis may also be the result of kidney disease in people who have undergone long-term dialysis.
The exact cause of amyloidosis is unknown, and currently there is no cure for the disease. However, medications and special diets may help relieve symptoms and reduce the production of the amyloid protein.
The type of precursor protein, the tissue distribution, and the amount of amyloid deposition largely determine the clinical manifestations. In the two most common forms of systemic amyloidosis, primary (AL) and secondary (AA) amyloidosis, the major sites of clinically important amyloid deposition are in the kidneys, heart, and liver. In some disorders, clinically important amyloid deposition is limited to one organ.
Some clinical and laboratory features that suggest amyloidosis include waxy skin and easy bruising, enlarged muscles (eg, tongue, deltoids), symptoms and signs of heart failure, cardiac conduction abnormalities, hepatomegaly, evidence of heavy proteinuria or the nephrotic syndrome, peripheral and/or autonomic neuropathy, and impaired coagulation.
The prevalence of the most common types of amyloidosis varies in different parts of the world. In developed countries, AL is the most common type of systemic amyloidosis, while, in developing countries, AA amyloid is more frequent. This is a likely result of a higher burden of chronic infectious diseases such as tuberculosis, leprosy, and osteomyelitis in the latter.
• Westermark P. Review. Reflections on amyloidosis in Papua New Guinea. Philos Trans R Soc Lond B Biol Sci. 2008;363(1510):3701. (http://tinyurl.com/lnzh9vl).
The diagnosis of amyloidosis can be confirmed only by tissue biopsy, although the presence of amyloidosis may be suggested by the history and clinical manifestations (eg, nephrotic syndrome in a patient with multiple myeloma or long-standing, active rheumatoid arthritis). Biopsies may be directed to dysfunctional organs (eg, kidney, nerve) or to clinically uninvolved sites such as subcutaneous fat, minor salivary glands, or rectal mucosa.
Scintigraphy with radioisotope labeled serum amyloid P component (SAP) can identify the distribution of amyloid, and provide an estimate of the total body burden of fibrillar deposits.
• Hawkins PN. Serum amyloid P component scintigraphy for diagnosis and monitoring amyloidosis. Curr Opin Nephrol Hypertens. 2002;11(6):649. (http://tinyurl.com/kkzo2ea).
• Most people are diagnosed with amyloidosis after the age of 40.
• Men are much more likely (60-65%) than women to develop the disorder, according to the American Society of Hematology. The reason for this is unknown.
• Individuals who have a chronic infectious or inflammatory disease may be more likely to develop the disorder. For instance, 10-15% of people who have multiple myeloma (type of bone marrow cancer) develop amyloidosis.
• Since some forms of amyloidosis are inherited, individuals who have a family history of the disorder are often at an increased risk.
• Individuals who have kidney diseases that require kidney dialysis (especially if treatment lasts longer than five years) may be at increased risk for dialysis-associated amyloidosis. This is because dialysis cannot remove large proteins from the blood. Therefore, abnormal proteins may build up and deposit in surrounding tissues. However, this condition is rare with modern dialysis techniques.
Treatment of the different types of amyloidosis varies with the cause of fibril production. For the hereditary amyloidoses in which the mutant amyloid precursor protein is produced by the liver (eg, transthyretin, apolipoprotein A-I, and fibrinogen Aa), liver transplantation may in some instances prevent further deposition of amyloid and may lead to regression of established deposits.
A number of novel approaches to treatment are being investigated through in vitro drug screening and in animal models, and some have progressed through phase 2/3 clinical trials. They include agents that interfere with fibril formation; that inhibit the production of amyloidogenic precursors (eg, transthyretin, SAA); that hasten degradation of existing amyloid deposits (eg, immunotherapy); or that disrupt the interaction between amyloidogenic proteins and accessory molecules, such as heparan sulfate proteoglycans.
• Kolstoe SE. Drug targets for amyloidosis. Biochem Soc Trans. 2010;38(2):466. (http://tinyurl.com/muzx8cz).
Diflunisal, a commercially available generic nonsteroidal anti-inflammatory drug (NSAID), can stabilise transthyretin tetramers; in a randomized trial involving 130 patients with symptomatic FAP, it has also been shown at two years to significantly reduce the progression of neurologic impairment and to preserve quality of life, compared with placebo.
• Berk JL, et al. Repurposing diflunisal for familial amyloid polyneuropathy: a randomized clinical trial. JAMA. 2013 Dec;310(24):2658-67. (http://tinyurl.com/lj2n2gp).
The following information is taken from Natural Standard
Unclear or conflicting scientific evidence:
• DMSO (dimethyl sulfoxide): DMSO may change the course of amyloidosis if treatment is started early. However, there is not much scientific support for this claim.
• Use caution with urinary tract cancer or liver or kidney dysfunction. Avoid if allergic to DMSO or if pregnant or breastfeeding.
Traditional or theoretical uses lacking sufficient evidence:
• Germanium: Animal study suggests that germanium compounds may prevent amyloidosis. Results can only be considered preliminary at this time. Additional research is needed to make a conclusion.
• Avoid if allergic or hypersensitive to germanium, its compounds or germanium-containing plants. Avoid if pregnant or breastfeeding.
• Resveratrol: Preliminary data suggests that resveratrol may play a role in the prevention of amyloidosis. High quality clinical research is needed to better understand this relationship.
• Avoid if allergic or hypersensitive to resveratrol, grapes, red wine, or polyphenols. Resveratrol is generally considered safe and is commonly found in food and beverages. Use cautiously with bleeding disorders or abnormal blood pressure. Use cautiously with drugs that are broken down by the body’s cytochrome P450 system. Avoid if pregnant or breastfeeding.
The following supplements are suggested for you to consider in light of your relevant expertise and intimate understanding of the needs of your client or patient. They may be used in isolation or as part of a multi supplement strategy, but at all times the consideration of their use should be tied into the specific needs of the individual you are responsible for.
• Lumbrokinase (ARG): 2 caps, three times daily, away from food. (http://tinyurl.com/3pjcrnd).
• Intenzyme Forte (BRC): 3-5 tabs, three times daily, 45 min before or 2 hours after meals. (http://tinyurl.com/nqj2325).
• Metabolic-Zyme (ARG): 3-5 tabs, three times daily, 45 min before or 2 hours after meals. (http://tinyurl.com/942fg52).
• KappArest (BRC): 3 caps, three times daily, 20 min before meals. (http://tinyurl.com/ol78r2n).
o Note, contains trans-resveratrol
• Pro EFA oil (NN): 2 teaspoons daily with food. (http://tinyurl.com/cfo6uy5).
Antioxidant based upon the preliminary resveratrol research
• Pro-Berry Amla (ARG): 1 scoop, twice daily, with food. (http://tinyurl.com/d2aqkcd).
• Grape Pips (ARG): 3 caps, two-three times daily. (http://tinyurl.com/btfbhzc).
Registered Nutritional Therapist Helen Perks is collaborating with Clinical Education to bring you the first-ever Functional Medicine book club for Practitioners.
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