Rheumatoid Arthritis

Rheumatoid arthritis (RA) affects 1.3 million Americans.

75% of those affected are women.

Overall worldwide prevalence of RA is about 1%.

But some ethnic groups are more severely affected: up to 6% of Native Americans develop RA.

In 2-3% of those with RA, a close relative also has RA (i.e there is a 2-3x increase in risk for close relatives.)

Five years after the initial diagnosis, approximately 33% of patients are unable to work.

After 10 years of disease, approximately 50% have substantial functional disability.

Life expectancy is reduced by 5-10 years in those with RA.

RA is a disease of inflammation.

Let’s get better.

Subscribe to the Rheumatoid Arthritis Feedaccess rheumatoid arthritis information

Rheumatoid arthritis is a chronic, progressive autoimmune disorder characterized by inflammation of the joints and surrounding tissue. It may affect other organs as well.

Introduction to Banjo

Banjo provides fast, effective relief from pain and inflammation because it enables your body’s immune system to function properly. It works just like the fruits and vegetables you eat every day – by naturally inhibiting NF-kB, the inflammation Master Switch.

Banjo works better because it combines the most effective natural extracts and delivers them in a form that ensures maximum bio-availability. You get the full spectrum of phytonutrients your body needs to turn off excess inflammation.

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ALL RHEUMATOID ARTHRITIS POSTS

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Raw, vegan diet for fibromyalgia, rheumatoid arthritis

This is an essential publication because it supports the benefits of diet in providing symptom relief in fibromyalgia and rheumatoid arthritis.

In a nutshell ;-) those suffering with fibromyalgia or rheumatoid arthritis experienced a substantial improvement in their conditions when they switched to a raw, vegan diet. Specifically, they experienced a decrease in pain and stiffness and self-perception of their health was improved.

The problem, of course, is that this diet represents a substantial and some would say extreme departure from our ‘normal’ diet. A vegan diet includes no animal products whatsoever – no milk, eggs, butter. The “living food” diet studied here included only raw foods – no cooking whatsoever.

The obvious reality is that very few people will ever attempt such an extreme dietary modification, and fewer still will adhere to it. Nonetheless, it is one option, and might result in general improvement in conditions related to inflammation other than those specifically studied.

As an alternative, one might want to add more fruits and vegetables to the diet, especially fresh, raw fruits and vegetables. Supplements might be considered as well.

The publication:

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Toxicology. 2000 Nov 30;155(1-3):45-53.

Antioxidants in vegan diet and rheumatic disorders.

Hänninen, Kaartinen K, Rauma AL, Nenonen M, Törrönen R, Häkkinen AS, Adlercreutz H, Laakso J.

Department of Physiology, University of Kuopio, Finland.

Summary of the abstract

Plants are rich natural sources of antioxidants in addition to other nutrients. Interventions and cross sectional studies on subjects consuming uncooked vegan diet called living food (LF) have been carried out. LF is an uncooked vegan diet and consists of berries, fruits, vegetables and roots, nuts, germinated seeds and sprouts, i.e. rich sources of carotenoids, vitamins C and E.

The efficacy of LF in rheumatoid diseases was studied as an example of a health problem where inflammation is one of the main concerns.

The subjects eating LF showed highly increased levels of beta and alfa carotenes, lycopen and lutein in their sera. As the berry intake was 3-fold compared to controls the intake of polyphenolic compounds like quercetin, myricetin and kaempherol was much higher than in the omnivorous controls.

Those with fibromyalgia who changed to the LF diet experienced a decrease of their joint stiffness and pain as well as an improvement in perceived health and quality of life.

Rheumatoid arthritis patients eating the LF diet also reported similar positive responses and the objective measures supported this finding. The improvement of rheumatoid arthritis was significantly correlated with the day-to-day fluctuation of subjective symptoms.

In conclusion the rheumatoid patients subjectively benefited from the vegan diet. The improvements were consistent with objective measures.

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Alzheimer’s & arthritis – inflammation can’t turn off

Deficient NF-kB inhibitor (CARD8) in Alzheimer’s and rheumatoid arthritis

The two studies briefly summarized below are consistent with the theory that excess inflammation often results from the body’s inability to shut down NF-kB – the Master Switch of inflammation.

Turning on NF-kB results in inflammation. If NF-kB cannot be turned off, chronic inflammation results.

One of many ways the body turns off NF-kB is with a protein messenger known as “CARD8.” Normally, CARD8 is made when NF-kB is activated. The negative feedback loop (the result of turning on NF-kB is a product that feeds back and turns off NF-kB) is one reason inflammation does not normally get out of hand.

A genetic defect has been identified that results in less effective CARD8. Less effective CARD8 means the normal, negative feedback loop that helps keep inflammation in check is missing – so inflammation continues.

This defect in CARD8 has been identified as a contributor to Alzheimer’s and rheumatoid arthritis. Some studies have suggested that defective CARD8 might also be associated with Crohn’s disease.

What seems clear is that CARD8 is only one of many ways the body keeps inflammation in control. To the extent that this and other defects result in deficient NF-kB inhibitors, supplementing NF-kB inhibitors, as suggested on this site, might be helpful.

In the first study below, defective CARD8 was found to increase the risk of developing Alzheimer’s 2.4x in women.

In the second study below, defective CARD8 was found to predict the severity of rheumatoid arthritis.

The first publication:

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Dement Geriatr Cogn Disord. 2008;26(3):247-50. Epub 2008 Oct 8.

Deficiency of CARD8 is associated with increased Alzheimer’s disease risk in women.

Fontalba A, Gutiérrez O, Llorca J, Mateo I, Berciano J, Fernández-Luna JL, Combarros O.

Unidad de Genética Molecular, Marqués de Valdecilla University Hospital, Santander, Spain.

Summary of the abstract

NF-kB, a major transcription factor controlling inflammation, is activated in Alzheimer’s disease (AD) brains.

CARD8 protein has been implicated in the suppression of NF-kB activity, but a slight genetic alteration makes CARD8  non-functional and results in more active NF-kB and an amplification of the inflammatory process.

The major genetic risk factor of AD, is associated with hyperactivation of NF-kB and enhanced brain inflammation.

In a case-control study in 300 AD patients and 300 healthy controls, we examined whether the slight genetic alteration leading to non-functional CARD8 might predispose to AD. Women, but not men, had a 2.39-fold higher risk of developing AD than subjects without the alteration.

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The second publication:

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J Immunol. 2007 Oct 1;179(7):4867-73.

Deficiency of the NF-kappaB inhibitor caspase activating and recruitment domain 8 in patients with rheumatoid arthritis is associated with disease severity.

Fontalba A, Martinez-Taboada V, Gutierrez O, Pipaon C, Benito N, Balsa A, Blanco R, Fernandez-Luna JL.

Unidad de Genetica Molecular, Hospital Universitario Marques de Valdecilla, Santander, Spain.

Summary of the abstract

CARD8 potently inhibits NF-kappaB signaling, which plays a key role in inflammation, and may contribute to avoid a pathologic activation of NF-kB; however, the transcriptional mechanisms regulating CARD8 expression and the relevance of this protein in inflammatory diseases are poorly understood.

To study the relevance of CARD8 in chronic inflammatory disorders, we functionally characterized a deleterious polymorphism (p.C10X) and studied its association with rheumatoid arthritis (RA).

Deficiency of CARD8 was found to predict the severity of rheumatoid arthritis.

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NF-kB: Autoimmunity Master Switch

A review of NF-kB and autoimmune disease

The abstract below is a quick overview. It suggests the central importance of NF-kB and then lists a few of the autoimmune conditions related to excess NF-kB activation.

The full text article provides a more thorough review, and is available free online.

The full article includes a number of challenges and potential dangers associated with pharmaceutical inhibition of NF-kB. Please note, however, that on this site I’m mainly discussing NF-kB inhibition by means of natural extracts. You’re already doing that – every day – it’s just that you might not be doing enough of it, especially since we’re all exposed to more inflammation promoters every day.

Of course natural extracts are not necessarily safe. Some can have side effects at high doses, and some are outright poisonous.

So as an added safety precaution, Banjo uses only those ingredients that have at least a 1,000 year history of safe use and for which no dose, however great, has ever been found unsafe. Then Banjo uses a relatively small amount of each extract, but in combination with a unique “trans-mucosal” delivery system, it’s very effective.

So yes – NF-kB inhibition by synthetic pharmaceuticals will probably cause all sorts of side effects.

But the natural extracts? If it was possible to overdose I’d be long gone. I drink a lot of coffee.

The publication:

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Acta Biochim Pol. 2008;55(4):629-47. Epub 2008 Dec 16.

The role of nuclear factor-kappaB in the development of autoimmune diseases: a link between genes and environment.

Kuryłowicz A, Nauman J.

Summary of the abstract (or you can read the free full text online)

Although autoimmune diseases are relatively common, mechanisms that lead to their development remain largely unknown.

Nuclear factor-kappaB (NF-kappaB), as a key transcription factor involved in the regulation of immune responses and apoptosis, appears to be a good candidate for studies on the pathogenesis of autoimmunity.

This review presents how perturbations of the NF-kappaB signaling pathway may contribute to self-tolerance failure, initiation of autoimmune inflammatory response as well as its persistent maintenance and therefore to the development of common autoimmune diseases including:

  • rheumatoid arthritis
  • multiple sclerosis
  • diabetes
  • thyroid autoimmune diseases
  • lupus
  • inflammatory bowel diseases
  • and psoriasis

A special emphasis is put on the genetic variations in the NF-kappaB related genes and their possible association with susceptibility to autoimmune diseases, as well as on the therapeutic potential of the NF-kappaB targeted strategies in the treatment of autoimmunity.

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Turmeric as wonder drug

Curcumin is the active ingredient of turmeric that has been consumed as a dietary spice for ages.

Curcumin, or turmeric, is believed to have many beneficial effects relative to inflammation and disease. It is an inhibitor of NF-kB, but also affects other pathways and mediators of inflammation.

The publication:

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Adv Exp Med Biol. 2007;595:127-48.

Modulation of transcription factors by curcumin.

Shishodia S, Singh T, Chaturvedi MM.

Summary of the abstract

Curcumin is the active ingredient of turmeric that has been consumed as a dietary spice for ages.

Turmeric is widely used in traditional Indian medicine to cure biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis.

Extensive investigation over the last five decades has indicated that curcumin:

  • reduces blood cholesterol
  • prevents low-density lipoprotein oxidation
  • inhibits platelet aggregation
  • suppresses thrombosis and myocardial infarction

And that it suppresses symptoms associated with:

  • type II diabetes
  • rheumatoid arthritis
  • multiple sclerosis
  • Alzheimer’s disease

And that it:

  • inhibits HIV replication
  • enhances wound healing
  • protects from liver injury
  • increases bile secretion
  • protects from cataract formation
  • protects from pulmonary toxicity and fibrosis.

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Comments:

You’re taking a daily dose of curcumin, right?

The only ‘problem’ with curcumin seems to be its low level of bio-availability. That is, not enough curcumin gets into the blood, and to the cells where it can exert its  beneficial effects.

Banjo delivers turmeric (and curcumin, its major active ingredient) trans-mucosaly. That is, the active ingredients are absorbed through the mucous membranes of the mouth. This is believed to substantially increase the bio-availability of all active agents, resulting in a much more effective product.

That’s why Banjo is provided as a lozenge that is held in your mouth until dissolved. Active ingredients coat the mucous membrane lining your mouth, and are absorbed through that mucous membrane while the lozenge dissolves.

If you prefer, the Banjo lozenge can instead be dissolved in water to make a great tasting ‘tea.’ By slowly sipping the tea you achieve the same effect, as the tea coats the membranes of your mouth, allowing active ingredients to be absorbed.

This method of administration bypasses the harsh environment of the stomach and avoids immediate destruction of active ingredients by the liver.

Active ingredients are very rapidly absorbed – directly into the bloodstream. That’s one reason why banjo acts so quickly. Significant relief from pain and inflammation often results within minutes.

Curcumin: Great effects – no side effects

Efficacy of curcumin demonstrated in rheumatoid arthritis, inflammatory eye diseases, inflammatory bowel disease, chronic pancreatitis, psoriasis, hyperlipidemia, and cancers

Patients taking up to 8 grams of pure curcumin daily for 4 months reported no significant side effects.

The publication:

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Adv Exp Med Biol. 2007;595:471-80.

Clinical studies with curcumin

Hsu CH, Cheng AL.

Summary of the abstract

Curcumin has long been expected to be a therapeutic or preventive agent for several major human diseases because of its antioxidative, anti-inflammatory, and anticancerous effects.

In phase I clinical studies, curcumin with doses up to 3600-8000 mg daily for 4 months did not result in discernible toxicities except mild nausea and diarrhea.

The pharmacokinetic studies of curcumin indicated in general a low bioavailability of curcumin.

The effect of curcumin was studied in patients with rheumatoid arthritis, inflammatory eye diseases, inflammatory bowel disease, chronic pancreatitis, psoriasis, hyperlipidemia, and cancers.

Although the preliminary results did support the efficacy of curcumin in these diseases, the data to date are all preliminary and not conclusive. It is imperative that well-designed clinical trials, supported by better formulations of curcumin or novel routes of administration, be conducted in the near future.

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Comments:

The only ‘problem’ with curcumin is solved by a novel route of administration

The only ‘problem’ with curcumin seems to be its low level of bio-availability. That is, not enough curcumin gets into the blood, and to the cells where it can exert its  beneficial effects.

Banjo delivers turmeric (and curcumin, its major active ingredient) trans-mucosaly. That is, the active ingredients are absorbed through the mucous membranes of the mouth. This is believed to substantially increase the bio-availability of all active agents, resulting in a much more effective product.

That’s why Banjo is provided as a lozenge that is held in your mouth until dissolved. Active ingredients coat the mucous membrane lining your mouth, and are absorbed through that mucous membrane while the lozenge dissolves.

If you prefer, the Banjo lozenge can instead be dissolved in water to make a great tasting ‘tea.’ By slowly sipping the tea you achieve the same effect, as the tea coats the membranes of your mouth, allowing active ingredients to be absorbed.

This method of administration bypasses the harsh environment of the stomach and avoids immediate destruction of active ingredients by the liver.

Active ingredients are very rapidly absorbed – directly into the bloodstream. That’s one reason why Banjo acts so quickly. Significant relief from pain and inflammation often results within minutes.

Turmeric reduces synovial hyperplasia

Curcumin – one of the major active components of turmeric – reduced synovial hyperplasia in rheumatoid arthritis

The synovium is normally a very thin, smooth layer of cells that is closely attached to the membrane that encloses the joint and its synovial (lubricating) fluid.

In rheumatoid arthritis the synovium becomes thickened and develops finger-like projections extending out into the joint space. This thickening process is called “hyperplasia,”and typically leads to pannus formation. Pannus means “flap” – and the pannus in rhuematoid arthritis contributes to the joint destruction characteristic of that disease.

One reason the synovium may thicken is that old cells do not die as they are supposed to. So as new cells continue to be made, cells accumulate.

While it might seem strange that cell death is required to maintain health, such is often the case. This “programmed cell death” is called “apoptosis.”

The classic example of cells that do not die as they are supposed to is cancer. In cancer cells, the gene that programs for cell death (apoptosis) has somehow been turned off. So cancer cells live, and proliferate, forever.

The synovial cells in rheumatoid arthritis act like cancer cells in certain ways. They continue to reproduce and live ‘forever.’ They invade and destroy nearby tissue. And what’s ‘nearby’ is the cartilage of the joint capsule.

This, in brief, is how synovial hyperplasia leads to joint destruction. Of course preventing this hyperplasia would be a very good thing.

The publication:

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nt J Mol Med. 2007 Sep;20(3):365-72.

Curcumin induces apoptosis and inhibits prostaglandin E(2) production in synovial fibroblasts of patients with rheumatoid arthritis.

Summary of the abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease that is characterized by hyperplasia of the synovial fibroblasts, which is partly the result of decreased apoptosis.

This study investigated the mechanisms through which curcumin, a polyphenolic compound from the rhizome of Curcuma longa, exerts its anti-proliferative action in the synovial fibroblasts obtained from patients with RA.

Exposure of the synovial fibroblasts to curcumin resulted in growth inhibition and the induction of apoptosis.

Curcumin decreased the expression levels of the cyclooxygenase (COX)-2 mRNA and protein without causing significant changes in the COX-1 levels, which was correlated with the inhibition of prostaglandin E(2) synthesis.

These results show that curcumin might help identify a new therapeutic pathway against hyperplasia of the synovial fibroblasts in RA.

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Comments:

Curcumin was found to stimulate apoptosis – the programmed cell death that is required if synovial cells are to remain as a nice smooth layer and not build up into a joint-destroying pannus.That is, it seemed to make the synovial cells behave properly.

As something of a ’side benefit’ – curcumin was found to inhibit COX-2 without affecting levels of COX-1. COX-1 is required for stomach protection. By inhibiting only COX-2 one would obtain the analgesic and anti-inflammatory benefits without the stomach-related (and kidney related) side effects common to aspirin and other NSAIDs.

Turmeric in autoimmune disease

curcumin turmeric

Turmeric (curcumin) shown to improve multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease

Let’s take a look at a recent publication that briefly reviews curcumin for autoimmune disease.

We’ll see that curcumin (an active ingredient in turmeric,) is recognized as safe, and that it has recently been shown to be effective against several serious conditions in human and/or animal studies.

That sounds promising. But your doctor will never have a chance to prescribe it for you. Why might that be?

Let’s start by taking a look at the abstract.

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Bright JJ., Adv Exp Med Biol. 2007;595:425-51.

Curcumin and autoimmune disease

Summary of the abstract

A breakdown in the immune system often results in infection, cancer, and autoimmune diseases. Multiple sclerosis, rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, myocarditis, thyroiditis, uveitis, systemic lupus erythromatosis, and myasthenia gravis are organ-specific autoimmune diseases that afflict more than 5% of the population worldwide.

Although the etiology (cause) is not known and a cure is still wanting, the use of herbal and dietary supplements is on the rise in patients with autoimmune diseases, mainly because they are effective, inexpensive, and relatively safe.

Curcumin is a polyphenolic compound isolated from the rhizome of the plant Curcuma longa (turmeric) that has traditionally been used for pain and wound-healing. Recent studies have shown that curcumin ameliorates (improves, helps with) multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease in human or animal models.

Curcumin inhibits these autoimmune diseases by regulating inflammatory cytokines such as IL-1beta, IL-6, IL-12, TNF-alpha and IFN-gamma and associated JAK-STAT, AP-1, and NF-kappaB signaling pathways in immune cells.

Although the beneficial effects of nutraceuticals are traditionally achieved through dietary consumption at low levels for long periods of time, the use of purified active compounds such as curcumin at higher doses for therapeutic purposes needs extreme caution. A precise understanding of effective dose, safe regiment, and mechanism of action is required for the use of curcumin in the treatment of human autoimmune diseases.

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The history and likely future of curcumin (turmeric)

The list of disease conditions associated with “a breakdown” of the immune system is sobering. That these very serious, often debilitating and sometimes life threatening conditions collectively effect 5% of the world population should emphasize the urgency with which this problem must be addressed.

The author next observes that dietary supplement use is on the rise. Hardly surprising given the author’s assessment that they are “effective, inexpensive, and relatively safe.”

Next comes a list the conditions for which curcumin (a component of turmeric) seems to be effective, followed by a brief explanation of how curcumin generally affects the immune system – by regulating inflammation.

Given all this, we must be well on our way to a new, effective treatment for these devastating conditions. Very exciting.

But no. Using higher doses for therapeutic treatment requires “extreme caution.” (Not just caution, mind you – “extreme” caution.) We can’t do anything, it seems, until we first have a precise understanding of the effective dose, safe regiment, and mechanism of action. (Not just an understanding – a “precise” understanding.)

I don’t want to seem as if I’m picking on this author. I’m not. I very much appreciate the review.

And I don’t disagree regarding the need for caution, especially when one component of a plant (in this case curcumin) is given in concentrated form. I think the full-spectrum extract (e.g. as used in Banjo) is a better, more effective, safer alternative. I also don’t think that “higher doses” are required. But if you think they are, you can purchase essentially pure curcumin – today – in any health food store. Thousands use curcumin each day, and there are no significant side effects associated with its use.

What I object to is that natural products are viewed with such suspicion. Rather than expressing excitement over what might be an effective treatment for conditions that currently devastate the lives of millions – and for which there are few if any good treatments – only “extreme caution” is recommended. Yes, let’s be cautious – always. But let’s also recognize that curcumin has been in a real world ‘clinical trial’ for thousands of years and that it has performed well. Let’s not throw up artificial, unrealistic barriers to its use, such as the need to “precisely understand” its mechanism of action.

Here are the number of prescription pharmaceuticals for which we “precisely understand” the mechanism of action: 0.

OK, there might be a few where our understanding could be called “precise” – but there are far more where the mechanism of action is entirely unknown. The FDA does not require that the precise mechanism of action be known as a condition of new drug approval. They do require a showing of “safety and efficacy.”

Curcumin (turmeric) has a long history of safe use and is reported by thousands (millions?) to be effective. Additionally, as the author notes, a number of recent studies in animals and humans have shown it to be effective.

Given all this, it seems not much additional work should be required to determine the best dose at which curcumin can be safely and effectively used – either for autoimmune disease or the other many conditions for which it has been shown effective.

Not much work, relatively speaking – but there is a problem. No one is doing that work.

So it’s not just that you might have to wait a long time for your prescription for curcumin. It will never arrive.

That might be (should be) very distressing to you. But it should not lead you to believe what is not true. No, the drug companies do not want to keep you sick. No, there is not a conspiracy among doctors to hide the cure for cancer, or warts, or any other condition. Your doctor genuinely wants you to get well and the pharmaceutical companies genuinely want to offer new, effective drugs. Yes, the pharmaceutical company wants and needs profit – just like your doctor – just like me – just like you.

And that is the problem – or a large part of the problem. There is no economic model that supports development of prescription curcumin. The clinical trials required to satisfy the FDA would cost at least (I’m guessing) $30 million? $50 million? Far more, actually, because in addition to out of pocket expenses the FDA process would require substantial time and effort on the part of many pharmaceutical employees. Other projects would have to be deferred. And since curcumin cannot be patented, their investment would amount to a donation. Anyone could sell it. Walgreen’s would have it on the end cap in all their stores. Sales at GNC would be going gangbusters.

Given that this might be the greatest new drug in the last 50 years (or ever?) maybe you think some generous pharmaceutical company ’should’ make this donation – just for the good of the world. But you cannot believe they are malicious for not doing so. That would not be fair.

So while it’s probably true that no pharmaceutical company is working on curcumin, it’s also true that many are probably working with curcumin – trying to alter it so it becomes patentable. Maybe they can do that without diminishing its efficacy – and without creating a product that has serious side effects. Or maybe they can’t.

I guess we’ll just have to wait and see.

While we’re waiting, there’s turmeric (or curcumin.) Use it as you see fit – but realize you’re on your own.

Very few doctors are well-informed on turmeric (or any natural product,) and fewer still will advocate its use. You will not see television commercials for turmeric. Your insurance company will not pay for it.

You’re on your own. Is this a good thing? No, but it is what it is. You and I can rail against the system, or we can spend our efforts looking for what works – trying to get better.

Should you be cautious, educate yourself and act prudently? Of course. As much or more with this issue as with any other. And yes, there is some dangerous stuff out there. And yes, people do foolish things.

But don’t let anyone tell you that it’s wrong, or dangerous, or foolish to look for what works. Don’t let anyone tell you that you should suffer silently or that you should wait patiently for a drug that might never arrive – or might not arrive in time. That would not be fair.

Gooseberry for rheumatoid arthritis

Indian gooseberry recommended for bone disease – because it is an inhibitor of NF-kB

The publication:

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Ann N Y Acad Sci. 2009 Aug;1171:448-56.

Apoptosis of human primary osteoclasts treated with molecules targeting nuclear factor-kappaB

Summary of the abstract

Osteoclasts (OCs) are involved in several pathologies associated with bone loss, including rheumatoid arthritis, osteoporosis, bone metastasis of myeloma, osteosarcoma, and breast cancer.

In this review we determined the effects of natural compounds, including extracts from medicinal plants, on differentiation and survival of human primary osteoclasts.

With respect to effects of medicinal plants, we found that crude extracts of Emblica officinalis (Indian gooseberry) are able to induce specifically programmed cell death of mature osteoclasts.

Experiments demonstrate that E. officinalis extracts specifically compete with the binding of a transcription factor involved in osteoclastogenesis NF-kappaB to its specific target DNA sequences. This might explain the observed effects of E. officinalis on the expression levels of IL-6, an NF-kappaB-specific target gene.

We suggest the application of natural products as an alternative tool for therapy applied to bone diseases.

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Comments:

Extracts of Indian gooseberry inhibit function of NF-kB by competing at the binding site on the gene

Indian gooseberry has a long history of use as a medicinal plant. See the Wikipedia article on Indian gooseberry for more information.

When researched, plants with a long history of medicinal use are generally found to contain active agents. Not infrequently they are found to be mild inhibitors of NF-kB. In fact, when the plant has a history of use in the treatment of inflammation, it is most often found to act, at least in part, through inhibition of NF-kB.

Indeed, a great number of plant compounds are found to inhibit NF-kB.

These researchers investigated one specific effect – on osteoclasts (the cells responsible for breaking down bone) and found that a particular plant inhibits this bone destruction by inhibiting the activity of NF-kB.

They are right, I believe, to recommend the use of natural agents in the treatment of bone disease. Whether Indian gooseberry is the best option is uncertain.

NF-kB inhibition for rheumatoid arthritis

Two studies suggest the value and importance of NF-kB inhibition in the treatment of rheumatoid arthritis and osteoporosis

The first publication:

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Adv Exp Med Biol. 2009;649:100-13.

RANKL/RANK as key factors for osteoclast development and bone loss in arthropathies

Summary of the abstract

Osteoporosis or rheumatoid arthritis are bone diseases affecting hundreds of millions of people worldwide. Ground-breaking discoveries made in basic science over the last decade shed light on the molecular mechanisms of bone metabolism and bone turnover.

Three molecules, the receptor activator of NF-kappaB (RANK), its ligand (the thing that binds to and activates it) and the decoy receptor (the thing that inhibits it – keeps it from being turned on), have been a major focus of scientists and pharmaceutical companies alike, since experiments using mice in which these genes have been inactivated unanimously established their pivotal role as central regulators of osteoclast function. (Really good things happen when this is blocked.)

Consequently, novel drugs specifically targeting RANK-RANKL and their signaling pathways in osteoclasts are expected to revolutionize the treatment ofvarious bone diseases, such as cancer metastases, osteoporosis, or arthropathies.

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Comments:

Inhibition of NF-kB, by inhibiting the RANK pathway that turns it on, might have an enormous, beneficial impact on the treatment of rheumatoid arthritis and osteoporosis

The authors appear enthusiastic about the possibility of inhibiting NF-kB and how that might revolutionize treatment for hundreds of millions of people worldwide.

I share their enthusiasm.

The second publication:

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J Biol Chem. 2007 Jun 22;282(25):18245-53.

NF-kappaB p50 and p52 regulate receptor activator of NF-kappaB ligand (RANKL) and tumor necrosis factor-induced osteoclast precursor differentiation by activating c-Fos and NFATc1

Summary of the abstract or free full text publication

Postmenopausal osteoporosis and rheumatoid joint destruction result from increased osteoclast formation and bone resorption induced by receptor activator of NF-kappaB ligand (RANKL) and tumor necrosis factor (TNF).

Osteoclast formation induced by these cytokines requires NF-kappaB p50 and p52, c-Fos, and NFATc1 expression in osteoclast precursors.

The relationship between NF-kappaB and these other transcription factors in osteoclastogenesis remains poorly understood.

We conclude that NF-kappaB controls early osteoclast differentiation from precursors induced directly by RANKL and TNF, leading to activation of c-Fos followed by NFATc1.

Inhibition of NF-kappaB should prevent RANKL- and TNF-induced bone resorption.

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Comments:

Rheumatic joint destruction results from increased osteoclast formation that should be prevented by NF-kB inhibition

These authors sought to determine which transcription factors were really important. Their conclusion is that everything is controlled by NF-kB – that it is the Master Switch controlling joint destruction in rheumatoid arthritis.

Therefore the inhibition of NF-kB should prevent, or at least could prevent, joint destruction in rheumatoid arthritis.

Dandelion and turmeric in arthritis

Dandelion and turmeric inhibit bone resorption by inhibiting osteoclasts

The publication:

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Screening of Korean medicinal plants for possible osteoclastogenesis effects in vitro

Summary of the abstract or see the free full text publication

Bone undergoes continuous remodeling through bone formation and resorption, and maintaining the balance for skeletal rigidity. Bone resorption and loss are generally attributed to osteoclasts.

Differentiation of osteoclasts is regulated by receptor activator of nuclear factor NF-kB ligand (RANKL), a member of tumor necrosis factor family. When the balance is disturbed, pathological bone abnormality ensues.

Through the screening of traditional Korean medicinal plants, the effective molecules for inhibition and stimulation of RANKL-induced osteoclast differentiation in mouse bone marrow macrophages were identified. Among 222 methanol extracts, of medicinal plants, 10 samples exhibited ability to induce osteoclast differentiation.

In contrast, Curcuma longa (turmeric) and Taraxacum platycarpa (dandelion) showed inhibitory effects in RANKL-induced osteoclast differentiation.

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Comments:

Excess bone resorption is a characteristic of rheumatoid arthritis

Excessive osteoclastogenesis or activation of mature osteoclasts causes bone destruction. Excessive osteoclastogenesis is implicated as contributing to the pathology of rheumatoid arthritis and osteoporosis.

Prevention of excess osteoclast activity can be protective, especially in conditions like rheumatoid arthritis, characterized by excess bone resorption.

The present study suggests that dandelion and turmeric exert a bone protective effect the inhibition of NF-kB.

Better by Christmas – with Frankincense

At first it’s hard to believe that any one thing could effectively treat so many ailments. But since NF-kB inhibitors fight inflammation, it makes sense. If inflammation contributes to the cause of many conditions (and it does) then whatever relieves inflammation (actually treating the cause, not just masking the symptoms) should be effective in treating many ailments.

Read the full article »