What is an "Internet Troll"?

The Truth About Second Generation Copper-Peptides

Copper Peptides and Decrease of Cancer

Copper-Peptides Increase
Collagen

What is "Buried Skin Damage"?

Copper Peptides:
Effect on Normal Skin

Copper Protection Against
Alzheimer's Disease

Soy Peptides May Prevent
Age-Related Diseases

Dr. Pickart's Background

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Examples of Misinformation Spewed by an Internet Troll

We are in the process of responding to the questions that have a scientific answer. We will be adding to this page. Dr. Pickart has been very busy writing papers and currently has three papers on copper-peptides for skin accepted for publication in Europe. He is now working on the fourth paper.

The following are real posts and responses made recently on the EDS forum:

Topic: 2nd Generation Copper-Peptides

Note that the words used are at times exactly the same as used by ProCyte when attacking Skin Biology several years ago. See the our response to old ProCyte material below.

Posted by "Josee" the Troll
"...so called “second generation” copper peptides or copper chloride+hydrolyzed soy protein is not a real copper peptide, but a copper and protein complex. Unlike GHK-Cu, this copper complex is not naturally found in the body. Skin cells have no receptors to accept this molecule.

Therefore, it is broken down into free copper ions and protein fragments which apparently have little to no benefit for skin......Copper is a trace metal that can trigger edema, contact dermatitis, pro-oxidation by hydroxyl radicals & DNA damage if not bound to a particular peptide in a specific, controlled sequence. Copper complexes other than those naturally found in the body (such as GHK-Cu) have been found to promote double-strand DNA damage, dependent on their geometric structures and types of ligands..."

Josee also asserts that the 2nd generation copper peptides are inflammatory.

Answer:

Science Says
Dr. Howard Maibach tested these 2nd generation copper peptides on human skin. Four papers were published on positive actions of these copper peptides. These copper peptides also possessed strong anti-inflammatory actions. For Maibach's background see http://www.dermatology.ucsf.edu/faculty_staff/StaffBios/MaibachH.aspx.

1. In vivo nickel contact dermatitis: human model for topical therapeutics. Zhai, Chang, Singh, and Maibach (University of California, San Francisco, USA) Contact Dermatitis Vol. 40, pp. 205-208, 1999

Tested 2nd generation SRCPs on repair of human nickel allergy injured skin. Placebo-controlled double-blinded study found an accelerated the recovery of skin after injury and plus potent anti-inflammatory action.

2. Stripped skin model to predict irritation potential of topical agents in vivo in man. Zhai, Poblete, and Maibach (University of California, San Francisco, USA) International Journal of Dermatology, Volume 37, pages 386-389, 1998

Tested 2nd generation SRCPs on repair human tape stripped damaged skin. Placebo-controlled double-blinded study found an accelerated the rate of skin repair.

3. Sodium lauryl sulfate damaged skin in vivo in man: a water barrier repair model. Zhai, Leow, and Maibach (University of California, San Francisco, USA) Skin Research and Technology, Volume 4, pages 24-27, 1998

Tested 2nd generation SRCPs on repair of human 24-hour detergent damaged skin. Placebo-controlled double-blinded study found accelerated the rate of skin repair

4. Human barrier recovery after acute acetone perturbation: an irritant dermatitis model. Zhai, Leow, and Maibach (University of California, San Francisco, USA) Clinical and Experimental Dermatology, Volume 23, pages 11-13, 1998

Tested 2nd generation SRCPs on repair of human acetone damaged skin. Placebo-controlled double-blinded study found an accelerated the rate of skin repair.

I expect strong attacks on copper peptides from competing companies as the public realizes that, in addition to skin regenerative actions, copper peptides may also have anti-cancer actions. Look at the cancer section on www.skinbiology.com/copperpeptideregeneration.html. This will hurt the sales of many highly hyped cosmetic products. Many Trolls will be hired to attack copper peptides." - Dr. Pickart

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Topic: Copper and Copper-Peptides Decrease Cancer

In another awesome display of ignorance, "Josee the Troll" posted:

Well... since copper is also a potential carcinogen and copper peptides actually have made some tumor cells grow faster...

Answer:

Science Says

We had the 2nd generation copper peptides tested by the Shanghai Municipal Government testing facility and they were found to be non-carcinogenic.

GHK-copper was one of two compounds, among 1,309 compounds tested, that suppressed of cancer metastasis genes. GHK-copper the most effective and acted at the very low and non-toxic level of 1 micromolar. (Hong Y, Downey T, Eu KW, Koh PK, Cheah PY., Clin Exp Metastasis. 2010 Feb;27(2):83-90. A 'metastasis-prone' signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients and its implications for possible therapeutics.)

The Center for Disease Control states that "Copper has not been shown to cause cancer in people or animals". The International Agency for Research on Cancer has determined that copper is not classifiable as to human carcinogenicity. Added copper complexes reduce spontaneous colon cancer in rats and, when administered to tumor-bearing rats, slow the rate of tumor growth. In cell culture, copper complexes cause some types of cancer cells to revert to non-cancerous growth patterns.

In 1912, cancer patients in Germany were treated for facial epithelioma with a a blend of copper chloride and lecithin with some success. In 1913, researchers at at the University of Liverpool reported injections of a copper salt degenerated carcinomas transplanted into mice.

John R. J. Sorenson (University of Arkansas for Medical Sciences, College of Pharmacy) and colleagues treated rats with solid tumors with various copper complexes (such as copper salicylate) with SOD activity and this decreased tumor growth and increased survival rates in rats. These copper complexes did not kill cancer cells but often caused them to revert to the growth patterns of normal (differentiated) cells. (Sorenson, Prog Med Chem 1989; 26: 506-507) Sorenson also found that numerous copper complexes with SOD activity prevented or retarded the spontaneous development of cancers in mice and possessed anticancer, anti-carcinogenic, and anti-mutagenic effects both in vitro and in vivo. (Sorenson (ed.), Biology of Copper Complexes. Humana Press, Clifton, NJ. 1987)

The serum level of copper is often elevated in animals and humans with cancer (Inutsuka and Araki, Cancer 1978; 42: 626; Willingham and Sorenson, Tr Elem Med 1986; 3: 139-140.) It appears that this elevation of serum copper that occurs as a part of the body's response to the cancer, rather than its cause. Most tumor cells have decreased CuZnSOD activity compared to normal cells, and it has been suggested that the elevation in serum copper is a physiological response designed to activate CuZnSOD or other copper enzymes in cancer cells to inhibit their growth. (Oberley and Buettner, Cancer Res 1979; 39: 1141).

Colon cancer is the second most deadly cancer in the USA. When rats were fed low copper diets, they had a higher incidence of carcinogen-induced colon cancers compared with rats fed a high copper diet. (DiSilvestro, Greenson, Liao, Proc Soc Exp Biol Med 1992; 201: 94-99).

Also, APC is a gene known to suppress the formation of tumors and this gene is altered early on during colon cancer development. Familial adenomatous polyposis is a disease that has been linked to mutation changes in the APC gene. Individuals possessing these mutations develop numerous intestinal polyps (precancerous lesions) at an early age. A species of mice (Min or multiple intestinal neoplasia) have a mutation similar to the human gene (APC) that causes intestinal polyps and colon cancer. A study reported in 2001 by nutritionist Cindy D. Davis at the Human Nutrition Research Center (Grand Forks, N.D.) found that, when Min mice were fed a copper deficient diet (20% of normal level), they developed a significantly higher small intestine tumor incidence and a significantly higher small intestine tumor mass than mice fed adequate dietary copper. The low copper also decreased the expression of various protein kinase C isozymes, a series of proteins involved in the signal transduction pathway within the cell, thus upsetting normal cell regulation. Dr. Davis says these results have implications because 80% of the people in the USA do not ingest adequate amounts of copper.

Another study of copper deficiency in animals by Narayanan, Fitch and Levenson found that copper stimulates the production of the tumor-suppressor protein p53. This protein inhibits the growth of tumors in the body. (Narayanan, Fitch and Levenson, Dept. of Nutrition, Florida State U., Tallahassee, FL in The Journal of Nutrition, May 2001)

GHK-copper regenerative actions begin with its increase of protein P63 which maintains the proliferative capacity of adult stem cells.4 P63 is considered to have anti-senescence properties, foster genomic stability, and increase organismal longevity. The loss of P63 induces cellular senescence, and rapid, premature aging. (5-7) Interestingly, research suggests that P63 may suppress cancer. (8)

5. Su X, Flores ER. TAp63: The fountain of youth. Aging (Albany NY). 2009;1:866-9.
6. Keyes WM, Mills AA. p63: a new link between senescence and aging. Cell Cycle. 2006;5:260-5.
7. Beaudry VG, Attardi LD. SKP-ing TAp63: stem cell depletion, senescence, and premature aging. Cell Stem Cell. 2009;5:1-2.
8. Collavin L, Lunardi A, Del Sal G. p53-family proteins and their regulators: hubs and spokes in tumor suppression. Cell Death Differ. 2010 Apr 9. [Epub ahead of print] .

Further support for the role of GHK in cancer suppression is based on the small proteoglycan called decorin discovered as a molecule that helps regulate collagen synthesis. GHK-copper(+2) increases the production of decorin. (9) Apart of regulating collagen synthesis, decorin also possesses many regenerative and anti-inflammatory actions (regenerating nerves and muscles while suppressing scar formation) that are similar to the actions of GHK. However, decorin also suppresses tumor growth and metastasis of cancerous tissue (breast, prostate, osteosarcoma) in animal models. (10-26)
9. Siméon A, Wegrowski Y, Bontemps Y, Maquart FX. Expression of glycosaminoglycans and small proteoglycans in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu(2+). J Invest Dermatol. 2000;115:962-8.
10. Border WA, Noble NA, Yamamoto T, et al. Natural inhibitor of transforming growth factor-beta protects against scarring in experimental kidney disease. Nature. 1992;360:361-4.11. Logan A, Baird A, Berry M. Decorin attenuates gliotic scar formation in the rat cerebral hemisphere. Exp Neurol. 1999;159:504-10.
12. Fukui N, Fukuda A, Kojima K, et al. Suppression of fibrous adhesion by proteoglycan decorin. J Orthop Res. 2001;19:456-62.
13. Fukushima K, Badlani N, Usas A, et al. The use of an antifibrosis agent to improve muscle recovery after laceration. Am J Sports Med. 2001;29:394-402.
14. Grisanti S, Szurman P, Warga M, et al. Decorin modulates wound healing in experimental glaucoma filtration surgery: a pilot study. Invest Ophthalmol Vis Sci. 2005;46:191-6.
15. Weis SM, Zimmerman SD, Shah M, et al. A role for decorin in the remodeling of myocardial infarction. Matrix Biol. 2005;24:313-24.
16. Zhang Z, Garron TM, Li XJ, et al. Recombinant human decorin inhibits TGF-beta1-induced contraction of collagen lattice by hypertrophic scar fibroblasts. Burns. 2009;35:527-37.
17. Davies JE, Tang X, Denning JW, et al. Decorin suppresses neurocan, brevican, phosphacan and NG2 expression and promotes axon growth across adult rat spinal cord injuries. Eur J Neurosci. 2004;19:1226-42.
18. Minor K, Tang X, Kahrilas G, et al. Decorin promotes robust axon growth on inhibitory CSPGs and myelin via a direct effect on neurons. Neurobiol Dis. 2008;32:88-95.
19. Davies JE, Tang X, Bournat JC, Davies SJ. Decorin promotes plasminogen/plasmin expression within acute spinal cord injuries and by adult microglia in vitro. J Neurotrauma. 2006;23:397-408.
20. Li Y, Li J, Zhu J, Sun B, et al. Decorin gene transfer promotes muscle cell differentiation and muscle regeneration. Mol Ther. 2007;15:1616-22.
21. Reed CC, Waterhouse A, Kirby S, et al. Decorin prevents metastatic spreading of breast cancer. Oncogene. 2005;24:1104-10.
22. Shintani K, Matsumine A, Kusuzaki K, et al. Decorin suppresses lung metastases of murine osteosarcoma. Oncol Rep. 2008;19:1533-9.
23. Goldoni S, Seidler DG, Heath J, et al.An antimetastatic role for decorin in breast cancer. Am J Pathol. 2008;173:844-55.
24. Goldoni S, Iozzo RV. Tumor microenvironment: Modulation by decorin and related molecules harboring leucine-rich tandem motifs. Int J Cancer. 2008;123:2473-9.
25. Araki K, Wakabayashi H, Shintani K, et al. Decorin suppresses bone metastasis in a breast cancer cell line. Oncology. 2009;77:92-9.
26. Hu Y, Sun H, Owens RT, et al. Decorin suppresses prostate tumor growth through inhibition of epidermal growth factor and androgen receptor pathways. Neoplasia. 2009;11:1042-53.

Topic: How Copper-Peptides Increase Collagen

Posted by "Josee" the Troll
Actually there are a lot of processes during wound healing that are good for wound healing but not good outside of that situation.

For e.g. copper peptides stimulate MMPs. MMPs degrade collagen. In wound healing, this is actually good. When we injure ourselves, there's such a HUGE response to make collagen that it's done fast in disorganized arrays and also overdone. Hence we get scars. So a compound with MMPs activity is good because it might help degrade collagen and prevent the massive deposit.

But outside of wound healing, for anti-wrinking purposes for example, you want to keep your collagen, not degrade it so something with MMPs activity is something we want to avoid.

Answer:

Science Says
1. CPs increase collagen in normal skin

Effects of topical creams containing vitamin C, a copper-binding peptide cream and melatonin compared with tretinoin on the ultrastructure of normal skin - A pilot clinical, histologic, and ultrastructural study. Abdulghani A.A.; Sherr A.; Shirin S.; Solodkina G.; Tapia E.M.; Wolf.GottliebA.B.; Dermatology, UMDNJ, Robert Wood Johnson Medical School; Disease Management and Clinical Outcomes, 1998, 1:136-141.

A clinical study which compared the effect on the skin's production of collagen after using creams containing copper-peptides, vitamin C, or retinoic acid (retin-A) Twenty volunteers applied the various creams to their thighs daily for one month. New collagen production was determined by studying skin biopsy samples using immunohistological techniques. The study found, that after one month, copper-peptides had the most significant effect on collagen production. Significant increases in collagen production were found in 70% of the persons treated with copper-peptide creams, 50% of the persons treated with the vitamin C cream, and 40% of the persons treated with retinoic acid.

2. Other studies on skin

2.1 A Clinical Evaluation of a Copper-Peptide Containing Liquid Foundation and Cream Concealer Designed for Improving Skin Condition. Appa Y, Barkovic S, Finkey M B, Neutrogena Corporation, Los Angeles, CA, Stephens, T, TJ Stephens & Associates, Inc, Dallas, TX Abstract P66, American Academy of Dermatology Meeting, February 2002

GHK-Cu containing liquid foundation tested on skin appearance, skin elasticity and epidermal thickness in an 8 week study. GHK-Cu containing liquid foundation improved skin appearance, and increased skin elasticity and epidermal thickness.

2.2 The Effect of Tripeptide to Copper Ratio in Two Copper Peptide Creams on Photoaged Facial Skin. Leyden J, University of Pennsylvania, Philadelphia, PA, Grove, G, KGL, Inc/Skin Study Center, Broomall, PA; Barkovic S, Appa Y, Neutrogena Corporation, Los Angeles, CA; Abstract P67, American Academy of Dermatology Meeting, February 2002

GHK-Cu containing creams tested for reducing visible signs of aging and increasing skin density. GHK-Cu containing creams reduced visible signs of aging, decreased photodamage, and increased skin density in 8 weeks on facial skin.

2.3 Skin Care Benefits of Copper Peptide Containing Facial Cream. Leyden J, University of Pennsylvania, Philadelphia, PA Stephens T, Thomas J Stephens & Associates, Inc, Dallas, TX; Finkey MB, Barkovic S, Neutrogena Corporation, Los Angeles, CA; Abstract P68, American Academy of Dermatology Meeting, February 2002

GHK-Cu containing creams tested for effect on wrinkles, fine line, skin elasticity, skin density, and thickness. Placebo-controlled study, 71 females, 12 weeks. GHK-Cu containing creams reduced wrinkles and fine lines while increasing skin elasticity, skin density, and thickness.

2.4 Skin Care Benefits of Copper Peptide Containing Eye Creams. Leyden J, University of Pennsylvania, Philadelphia, PA; Stephens T, Thomas J Stephens & Associates, Inc, Dallas, TX; Finkey MB, Barkovic S, Neutrogena Corporation, Los Angeles, CA; Abstract P69, American Academy of Dermatology Meeting, February 2002

GHK-Cu containing eye creams tested on wrinkles, fine lines and eye appearance in placebo controlled study, 41 females, 12 weeks. In a second placebo controlled, 3 week, half face study, GHK-Cu was significantly better than a vitamin K cream. GHK-Cu containing eye creams reduced wrinkles and fine lines while improving eye appearance in placebo-controlled study. GHK-Cu was significantly better than a vitamin K cream.

2.5 Copper Peptide and Skin, M.B. Finkley, Y. Appa, S. Bhandarkar, Cosmeceuticals and Active Cosmetic, 2nd Edition (ISBN: 0-8247-4239-7), 2005, pp 549-563

A series of placebo-controlled studies found GHK-Cu skin creams to:
1. Tighten loose skin and improve elasticity
2. Improve skin density and firmness
3. Reduce fine lines and deep wrinkles 4. Improve skin clarity
5. Reduce photodamage and mottled hyperpigmentation
6. Strongly increase keratinocyte proliferation in women of 50 year old range

2.6 GHK-Cu reduced overall metalloproteinase activity. This activity is a result of the level of proteinases and anti-protease proteins. In wound studies, GHK-Cu actually reduced the level of activity. Remodeling of skin is the process of removing older skin and damage, then new cells and proteins are produced. Skin cannot be rebuilt without removing old proteins.

Copper peptides increase the production of MMPs and anti-proteases that block MMP actions. So the actual MMP activity depends on the balance of these two types of proteins. The only direct test of copper peptides and MMP activity is from a study in rats this idea was from a study in rats that found that the copper peptides actually decreased the activity of MMPs.

Vet Surg. 2003 Nov-Dec;32(6):515-23.
The effect of topical tripeptide-copper complex on healing of ischemic open wounds.

Canapp SO Jr, Farese JP, Schultz GS, Gowda S, Ishak AM, Swaim SF, Vangilder J, Lee-Ambrose L, Martin FG.
Department of Small Animal Clinical Sciences, University of Florida
College of Veterinary Medicine, and the School of Medicine Institute for
Wound Research, Gainesville, FL 32610, USA.
OBJECTIVE: To evaluate the effects of topical glycyl-L-histidyl-L-lysine tripeptide-copper complex (TCC; Iamin 2% Gel; Procyte Corporation, Redmond, WA) on healing in ischemic open wounds.
STUDY DESIGN: Experimental study. SAMPLE POPULATION: Twenty-four adult male Sprague-Dawley rats. METHODS: Rats were divided into 3 groups: topical TCC, topical TCC vehicle (hydroxypropyl-methylcellulose), and no treatment (control). Six-mm-diameter, full-thickness wounds were created within an ischemic bipedicle skin flap on the dorsum of each rat. Each day, for 13 days, wound margins were traced, and the TCC and TCC vehicle groups were treated topically. Tracings were scanned, and wound
perimeter and area were calculated. On days 6, 10, and 13, selected wounds were biopsied and analyzed for tumor necrosis factor alpha (TNF-alpha) and matrix metalloproteinases (MMP) 2 and 9.
RESULTS: A significant decrease in wound area was seen in the TCC group, but not the vehicle group, when compared with the control group on days 3 to 5, 6 to 9, and 11 to 13 and when TCC was compared with TCC vehicle on days 3 and 9. On day 13, initial wound area had decreased by 64.5% in the TCC group, 45.6% in the vehicle group, and 28.2% in the control group. On days 6, 10, and 13, TCC-treated wounds contained significantly lower concentrations of TNF-alpha and MMP-2 and MMP-9 than control wounds.
CONCLUSION: Topical TCC resulted in accelerated wound healing in ischemic open wounds.
CLINICAL RELEVANCE: Topical TCC is an effective stimulant of healing of ischemic open wounds in rats and may have an application for the treatment of chronic wounds in other species. Clinical evaluation of topical TCC is warranted.

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Topic: Buried Skin Damage:

Keliu wrote:
"It would seem to me that it's either medically possible to have "buried damage", or it is not. This is the 21st Century, someone must have worked it out by now. If there is no such thing as "buried damage", why has Dr Pickart devoted his career to curing it?"

"Josee" the Troll writes that there is no such thing as "Buried Skin Damage"
She says, "I think there's a difference between the claims to cure XYZ and the "theory" behind it.

For e.g. a claim is that copper peptides improve scars. And that is in theory something that the manufacturer has worked for.

Now a very different thing is people saying that when you start using Copper peptides you will get "uglies" (i.e your skin will look bad) because that's the damage (i.e. scars, broken collagen) somehow coming up through the epidermis and thus becoming visible Confused That theory has no biological basis."

Answer:

Science Says
See http://reverseskinaging.com/buried-skin-damage.html for examples of buried skin damage.

The Neutrogena studies at the University of Pennsylvania and UC San Francisco found that copper peptides removed photodamage a (which is primarily buried) and blemishes while reducing lines and wrinkles. See www.skinbiology.com/copperpeptideregeneration.html.

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Topic: Do Copper-Peptides Work on Normal Skin?

EDS Trolls say that copper peptides do not work on normal skin and there are no studies showing histological changes in the skin.

Answer:

Science Says
There is CP uptake information into human skin, safe studies, and many histological pictures in the article that is referenced on www.skinbiology.com/copperpeptideregeneration.html.

Copper Peptide and Skin, M.B. Finkley, Y. Appa, S. Bhandarkar, Cosmeceuticals and Active Cosmetic, 2nd Edition (ISBN: 0-8247-4239-7), 2005, pp 549-563. Any good medical library will have the book. The paper describes:

A series of placebo-controlled studies found GHK-Cu skin creams to:
1. Tighten loose skin and improve elasticity
2. Improve skin density and firmness
3. Reduce fine lines and deep wrinkles 4. Improve skin clarity
5. Reduce photodamage and mottled hyperpigmentation
6. Strongly increase keratinocyte proliferation in women of 50 year old range

- Dr. Pickart

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Topic: Copper-Peptides and Alzheimer's Disease?

EDS Trolls say that copper increases Alzheimer's Disease.

Answer:

Science Says
"Copper may protect against Alzehiemer's disease.

Excessive copper has been blamed for many diseases - heart disease, cancer, etc. The problem is that most of this comes from data on blood plasma copper and diseases. But usually, high blood plasma copper is associated with low tissue copper. Most plasma copper - 95% - is in ceruloplasmin - an acute phase reactant that rises with stress and disease. Available copper in the plasma is 5% of the plasma copper and on albumin.

In every case so far, when all the data came in on a disease, it was found that higher tissue copper reduced the disease or condition.

For years, a German physician was preaching that copper caused Alzheimer's. Then a lab said rabbits fed cholesterol and copper developed brain plaques. This led to some very good studies in the best Alzheimer's research labs in Germany, Canada, and the USA and these labs came to the opposite conclusion; that more copper reduced brain plaques.

But the best study was one that gave supplemental copper to Alzheimer's patients. Those given more copper, had less mental decay. 8 mgs of supplemental copper daily is safe in the Alzheimer's patients. See below.

Newer studies have found that more copper 2+ blocks the formation of plaques. See below.

1. Science News
Protective Role For Copper In Alzheimer’s Disease

ScienceDaily (Oct. 13, 2009) — Two articles in a forthcoming issue of the Journal of Alzheimer’s Disease -- by Dr Chris Exley, Reader in Bioinorganic Chemistry in the Research Institute for the Environment, Physical Sciences and Applied Mathematics at Keele University, UK, and Dr Zhao-Feng Jiang, of Beijing Union University, Beijing, China -- have confirmed a potentially protective role for copper in Alzheimer’s disease.

Previous research has shown that copper is one component of the amyloid beta plaques which are found in the brains of people of Alzheimer’s disease.

A central tenet of the Amyloid Cascade Hypothesis of Alzheimer’s disease is the aberrant deposition in the brain of Aβ42 in β-sheets in neuritic or senile plaques. The Keele team have shown in previous research in JAD that copper (Cu(II)) prevents the deposition of Aβ42 in β-sheets while in the current research they show that Cu(II) abolishes the β-sheet structure of preformed amyloid fibrils of Aβ42. A similar finding was made by the group of Jiang for the other form of beta amyloid, Aβ40, and together these observations strongly suggest that copper prevents both the formation and the accumulation of plaques in the brain.

Coincident with the copper-catalysed dissolution of β-sheets of Aβ42, Exley’s group made the first observation of the in vitro formation of spherulites of this peptide. These spherical globules of amyloid have only previously been observed in vitro for the other amyloid-forming proteins insulin and β-lactoglobulin. Copper appeared to have a role in the formation of spherulites of Aβ42 and this will be investigated in future research. The role of metals in the formation, deposition and metabolism of Aβ in Alzheimer’s disease is much debated and these new findings highlight a potential protective role for copper in Alzheimer’s disease.

2. JOURNAL OF ALZHEIMER'S DISEASE
Volume 18, Number 4, December 2009
Pages 811-817
Emily House, Matthew Mold, Joanna Collingwood, Alex Baldwin, Steven Goodwin, Christopher Exley
Copper Abolishes the β-Sheet Secondary Structure of Preformed Amyloid Fibrils of Amyloid-β42
Abstract: The observation of the co-deposition of metals and amyloid-β42 (Aβ42) in brain tissue in Alzheimer’s disease prompted a myriad of investigations into the role played by metals in the precipitation of this peptide. Copper is bound by monomeric Aβ42 and upon precipitation of the copper-peptide complex thereby prevents Aβ42 from adopting a β-sheet secondary structure. Copper is also bound by β-sheet conformers of Aβ42, and herein we have investigated how this interaction affects the conformation of the precipitated peptide. Copper significantly reduced the thioflavin T fluorescence of aged, fibrillar Aβ42 with, for example, a 20-fold excess of the metal resulting in a ca 90% reduction in thioflavin T fluorescence. Transmission electron microscopy showed that copper significantly reduced the quantities of amyloid fibrils while Congo red staining and polarized light demonstrated a copper-induced abolition of apple-green birefringence. Microscopy under cross-polarized light also revealed the first observation of spherulites of Aβ42. The size and appearance of these amyloid structures were found to be very similar to spherulites identified in Alzheimer’s disease tissue. The combined results of these complementary methods strongly suggested that copper abolished the β-sheet secondary structure of pre-formed, aged amyloid fibrils of Aβ42. Copper may protect against the presence of β-sheets of Aβ42 in vivo, and its binding by fibrillar Aβ42 could have implications for Alzheimer’s disease therapy.

3. Increased dietary copper have a slightly positive effect on Alzheimer's patients

J Neural Transm. 2008 Dec;115(12):1651-9. Epub 2008 Oct 30.
Effect of copper intake on CSF parameters in patients with mild Alzheimer's disease: a pilot phase 2 clinical trial.

Kessler H, Pajonk FG, Bach D, Schneider-Axmann T, Falkai P, Herrmann W, Multhaup G, Wiltfang J, Schäfer S, Wirths O, Bayer TA.

Department of Psychiatry and Psychotherapy, Saarland University Hospital, Homburg/Saar, Germany.

A plethora of reports suggest that copper (Cu) homeostasis is disturbed in Alzheimer's disease (AD). In the present report we evaluated the efficacy of oral Cu supplementation on CSF biomarkers for AD. In a prospective, randomized, double-blind, placebo-controlled phase 2 clinical trial (12 months long) patients with mild AD received either Cu-(II)-orotate-dihydrate (verum group; 8 mg Cu daily) or placebo (placebo group). The primary outcome measures in CSF were Abeta42, Tau and Phospho-Tau. The clinical trial demonstrates that long-term oral intake of 8 mg Cu can be excluded as a risk factor for AD based on CSF biomarker analysis. Cu intake had no effect on the progression of Tau and Phospho-Tau levels in CSF. While Abeta42 levels declined by 30% in the placebo group (P = 0.001), they decreased only by 10% (P = 0.04) in the verum group. Since decreased CSF Abeta42 is a diagnostic marker for AD, this observation may indicate that Cu treatment had a positive effect on a relevant AD biomarker. Using mini-mental state examination (MMSE) and Alzheimer disease assessment scale-cognitive subscale (ADAS-cog) we have previously demonstrated that there are no Cu treatment effects on cognitive performance, however. Finally, CSF Abeta42 levels declined significantly in both groups within 12 months supporting the notion that CSF Abeta42 may be valid not only for diagnostic but also for prognostic purposes in AD.

4. Science News
Intake Of Dietary Copper Helps Alzheimer's Patients
ScienceDaily (Oct. 4, 2005) — As one of the services for patients with Alzheimer's disease, the Department of Psychiatry at the Saarland University Medical Center offers participation in a clinical phase II trial. This clinical trial aims to elucidate a potential beneficial effect of copper orotate (an organic copper salt), which is given together with a standard cholinesterase inhibitor. A diagnosis of mild to moderate dementia of the Alzheimer type is a prerequisite. Besides clinical investigations, laboratory investigations of blood and cerebrospinal fluid, and magnet resonance imaging of the brain will be carried out. The study is being conducted by Professor Dr. Thomas Bayer, the Head of the Division of Neurobiology, and Dr. Frank Pajonk, a Psychiatrist, at the Department of Psychiatry, Saarland University Medical Center.

Treatment starts after all prerequisites to participate have been met. Half of the patients receive 8 mg copper orotate per day, the other half a placebo. Both patients and psychiatrists are blinded. During the 12-month long double-blind phase, there will be extensive laboratory, clinical and neuropsychological tests. After the double-blind phase, we offer an open-label phase for all patients. At present, 15 patients have finished the double-blind phase. The copper medication is well tolerated.

Alzheimer is characterized by the presence of amyloid plaques, which are composed primarily of Aß peptide. Aß is produced within neurons and is liberated from the larger amyloid ß protein precursor (AßPP). Lower levels of copper have been reported in the brain of AßPP transgenic mice and post-mortem in AD patients. This concept has been found to be true also in vitro by Professor Dr. Gerd Multhaup (FU Berlin) in 1999. Two recent papers, which have been published in PNAS in 2003 have proven a beneficial effect of elevated copper in transgenic AßPP mice. In the present study, the teams led by Bayer and Multhaup have found that low copper level in blood correlates with advanced memory deficits, as tested by the well established ADAS-cog neuropsychological test battery. Patients with higher blood copper levels make fewer mistakes in this memory test. This result supports the notion of a mild copper deficiency in AD patients. An increased uptake of dietary copper may therefore be therapeutically relevant.

The study has been published in the September 2005 issue of the Journal of Alzheimer's Disease, Volume 8, Issue 1 published by IOS Press: "Cognitive decline correlates with low plasma concentrations of copper in patients with mild to moderate Alzheimer's disease" (JAD, Vol. 8, Issue 1).

5. Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14187-92. Epub 2003 Nov 14.
Dietary Cu stabilizes brain superoxide dismutase 1 activity and reduces amyloid Abeta production in APP23 transgenic mice.

Bayer TA, Schäfer S, Simons A, Kemmling A, Kamer T, Tepest R, Eckert A, Schüssel K, Eikenberg O, Sturchler-Pierrat C, Abramowski D, Staufenbiel M, Multhaup G.

Department of Psychiatry, Division of Neurobiology, University of the Saarland Medical Center, D-66421 Homburg, Germany. thomas.bayer@uniklinik-saarland.de

The Cu-binding beta-amyloid precursor protein (APP), and the amyloid Abeta peptide have been proposed to play a role in physiological metal regulation. There is accumulating evidence of an unbalanced Cu homeostasis with a causative or diagnostic link to Alzheimer's disease. Whereas elevated Cu levels are observed in APP knockout mice, APP overexpression results in reduced Cu in transgenic mouse brain. Moreover, Cu induces a decrease in Abeta levels in APP-transfected cells in vitro. To investigate the influence of bioavailable Cu, transgenic APP23 mice received an oral treatment with Cu-supplemented sucrose-sweetened drinking water (1). Chronic APP overexpression per se reduced superoxide dismutase 1 activity in transgenic mouse brain, which could be restored to normal levels after Cu treatment (2). A significant increase of brain Cu indicated its bioavailability on Cu treatment in APP23 mice, whereas Cu levels remained unaffected in littermate controls (3). Cu treatment lowered endogenous CNS Abeta before a detectable reduction of amyloid plaques. Thus, APP23 mice reveal APP-induced alterations linked to Cu homeostasis, which can be reversed by addition of dietary Cu.

6. Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14193-8. Epub 2003 Nov 14.
In vivo reduction of amyloid-beta by a mutant copper transporter.

Phinney AL, Drisaldi B, Schmidt SD, Lugowski S, Coronado V, Liang Y, Horne P, Yang J, Sekoulidis J, Coomaraswamy J, Chishti MA, Cox DW, Mathews PM, Nixon RA, Carlson GA, St George-Hyslop P, Westaway D.

Center for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada M5S 3H2.

Cu ions have been suggested to enhance the assembly and pathogenic potential of the Alzheimer's disease amyloid-beta (Abeta) peptide. To explore this relationship in vivo, toxic-milk (txJ) mice with a mutant ATPase7b transporter favoring elevated Cu levels were analyzed in combination with the transgenic (Tg) CRND8 amyloid precursor protein mice exhibiting robust Abeta deposition. Unexpectedly, TgCRND8 mice homozygous for the recessive txJ mutation examined at 6 months of age exhibited a reduced number of amyloid plaques and diminished plasma Abeta levels. In addition, homozygosity for txJ increased survival of young TgCRND8 mice and lowered endogenous CNS Abeta at times before detectable increases in Cu in the CNS. These data suggest that the beneficial effect of the txJ mutation on CNS Abeta burden may proceed by a previously undescribed mechanism, likely involving increased clearance of peripheral pools of Abeta peptide." - Dr. Pickart

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Topic: Are Soy Peptides Harmful?

EDS Trolls say that soy peptides are harmful

Answer:

Science Says
Soy peptides may actually prevent age-related chronic diseases

A New Frontier in Soy Bioactive Peptides that May Prevent Age-related Chronic Diseases
Wenyi Wang 1 Elvira Gonzalez de Mejia 1 1 Authors Wang and Mejia are with Dept. of Food Science and Human Nutrition, Univ. of Illinois at Urbana-Champaign, 228 ERML, MC-051, 1202 West Gregory Drive, Urbana-Champaign, IL 61801.

During gastrointestinal digestion or food processing of proteins, small peptides can be released and may act as regulatory compounds with hormone-like activities. Numerous biologically active peptides (bioactive peptides) have been identified. Most bioactive peptides are derived from milk and dairy products, with the most common being angiotensin converting enzyme inhibitory peptides. Soybean protein and soybean derived peptides also play an important role in soybean physiological activities, particularly those related to the prevention of chronic diseases. However, the bioactive potential of soybean derived bioactive peptides is yet to be fully appreciated. After a general introduction of approaches and advances in bioactive peptides from food sources, this review focuses on bioactive peptides derived from soybean proteins and their physiological properties. Technological approaches to generate bioactive peptides, their isolation, purification, characterization, and quantification, and further application in food and drug design are also presented. Safety concerns, such as potential toxicity, allergenicity, and sensory aspect of these peptides are likewise discussed.

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