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Rheumatoid Arthritis and Osteoporosis: A Case Study

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Metadichol® is a Nano emulsion of long-chain alcohols called as Policosanol and is present in foods such as rice, sugar cane, wheat, and peanuts. Metadichol® acts on Nuclear Vitamin D receptors (VDR) that are present in cells throughout the body to stimulate the immune system and inhibit a variety of disease processes, resulting from inflammation to infection [1]. We present a case study of a patient with Rheumatoid arthritis with the high levels of RF antibodies, CRP and ESR levels, and low bone mineral density leading to osteoporosis. The case report shows how Metadichol® by its actions on the VDR has affected key biomarkers and mitigated the disease conditions without any side effects. Also, his bone density improved dramatically. Metadichol® is safe because it consists of natural components of conventional foods and has no known adverse side effects. Its constituents are present in many foods that we consume every day. Metadichol® has the potential to serve as a novel, safe solution to help patients with RA and other autoimmune diseases that confront the world today.
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Rheumatoid Arthritis and Osteoporosis: A Case Study
PR Raghavan*
Nanorx Inc., New York, USA
*Corresponding author: PR Raghavan, Nanorx Inc., PO Box 131 Chappaqua, New York 10514, USA, Tel: +1-914-671-0224; E-mail: raghavan@nanorxinc.com
Received date: April 21, 2017; Accepted date: April 25, 2017; Published date: May 5, 2017
Copyright: © 2017 Raghavan. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Metadichol® is a Nano emulsion of long-chain alcohols called as Policosanol and is present in foods such as rice,
sugar cane, wheat, and peanuts. Metadichol® acts on Nuclear Vitamin D receptors (VDR) that are present in cells
throughout the body to stimulate the immune system and inhibit a variety of disease processes, resulting from
inflammation to infection [1].
We present a case study of a patient with Rheumatoid arthritis with the high levels of RF antibodies, CRP and
ESR levels, and low bone mineral density leading to osteoporosis. The case report shows how Metadichol® by its
actions on the VDR has affected key biomarkers and mitigated the disease conditions without any side effects. Also,
his bone density improved dramatically.
Metadichol® is safe because it consists of natural components of conventional foods and has no known adverse
side effects. Its constituents are present in many foods that we consume every day.
Metadichol® has the potential to serve as a novel, safe solution to help patients with RA and other autoimmune
diseases that confront the world today.
Keywords: VDR; Vitamin D; Metadichol®; Innate immunity; Inverse
agonist; Protean agonist; Nano emulsion; Long chain lipid alcohols; RA
factor; ESR; hS-CRP; TNF-alpha Inhibitors; Osteoporosis; Bone
mineral density; BMD
Introduction
Rheumatoid arthritis is a chronic inammatory disease in which the
synovial membrane of the joint becomes inamed, resulting in a
swelling, stiness, pain, limited motion, joint deformity, and disability.
RA is the most common inammatory arthritis across the world and is
an autoimmune disease, in which a person's immune system attacks
his or her healthy tissues .
ere is no known cure for rheumatoid arthritis, and spontaneous
remission in a stable disease is rare. e goal of treatment is today is to
alleviate the current symptoms and prevent the future destruction of
the joints. Pain Relievers do not have any impact on the long-term
consequences.
Clinically the Erythrocyte Sedimentation Rate (ESR), C-reactive
protein, full blood count, renal function, liver enzymes and other
immunological tests are also inammation indicators in RA patients
[2].
Vitamin D plays a role in infections also like tuberculosis and other
infectious like breast cancer, Vitamin D in conjunction with calcium
and phosphorus, maintains healthy bones. High levels of vitamin D
decrease the risk of autoimmune diseases, and the risk of rheumatoid
arthritis remains equivocal.
Major immune system-mediated rheumatic conditions such as RA
such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE)
are due to level of vitamin D which has an inverse correlation with the
conditions [3-5].
In Osteoporosis more bone is lost than replaced. is loss leads to
fragile bones. Osteoporosis patients have lower level of vitamin D in
comparison to those without this condition [6]. Increased Vitamin D
levels has been shown to prevent osteoporotic fractures. Currently,
bone mineral density (BMD) is the biomarker for osteopenia and
osteoporosis [7,8]. Vitamin D does not rebuild lost bone density but
only decrease rate of bone loss.
Vitamin D, through its active metabolite 1,25(OH)2D3 controls
both innate and adaptive immunity but supresses the adaptive
immunity [8,9]. Vitamin D with its immunomodulatory and anti-
inammatory properties is useful in treating RA patients. Vitamin D
inhibits 1 cells and upregulates 2 cells and can block
autoimmunity [10,11].
Vitamin D-binding protein (DBP) is a multifunctional plasma
protein with many essential functions. It transports vitamin D
metabolites, controls bone development, and helps in the binding of
fatty acids, sequestration of actin, and a range of less-dened roles in
modulating immune and inammatory responses [12]. It transports
vitamin D to liver, kidneys, bone, and other target tissues and increases
the half- life of the circulating vitamin D metabolites. As such, Vitamin
D metabolites are rmly correlated with DBP levels in serum [13].
DBP can also be converted to a macrophage activating factor (DBP-
MAF) by the deglycosylation of DBP that can modulate osteoclast
dierentiation and bone resorption by directly activating osteoclast.
DBP-MAF increase because of inammatory conditions that leads to
more osteoclast activity [14-17].
Journal of Arthritis Raghavan, J Arthritis 2017, 6:3
DOI: 10.4172/2167-7921.1000240
Case Report OMICS International
J Arthritis, an open access journal
ISSN:2167-7921
Volume 6 • Issue 3 • 1000240
TNF is another important cytokine that also has a role in host
response to inammatory conditions. It role in many in the
pathogenesis of inammatory diseases such as rheumatoid arthritis
(RA), psoriasis, psoriatic arthritis, and inammatory bowel disease is
well established [18].
Inhibition of TNF-α is an approach to treating rheumatoid arthritis
[18]. Iniximab®, Enrbel®, and Humira® are TNF-alpha inhibitors that
are FDA-approved for treatment of RA. TNF inhibition dramatically
reduces markers of inammation, but it also slows or halts the
structural damage which appears used to be as potent in early disease
as they are in late disease. ese drugs used for the treatment of
patients with chronic inammatory disorders. ere is however a
downside with an increased risk of Tuberculosis [19,20]. ere is a
need today for a safe and eective drug in treatment of such diseases.
Patient Case Presentation
We present here a case report on a 60 years old male patient with
rheumatoid arthritis for the last 18 years. Over the years, his condition
led to low bone mineral density, resulting in osteoporosis. His regular
treatment was monthly injections of cortisones and daily use of
Tylenol. e patient was not on any TNF-alpha inhibitors. Before
treatment with Metadichol his CRP level over 2+ years ago was all
normal (below 2), but it has started creeping up within the last two
years. Two weeks before treatment with Metadichol, his CRP level has
climbed from 27 to 83 (at baseline). Aer using Metadichol, his CRP
has dropped back to 2 within the rst 16 weeks and is remained under
control over the next 62 weeks. His ESR has also shown signicant
improvement from 105 at baseline to 80 at week 36 and 40 at week 78.
His RA Factor dropped from 698 at baseline to 190 at week 24, and 58
at week 78. e treatment results with Metadichol and the
improvement on his biomarkers are indicated in Figures 1-6.
Discussion
Metadichol rapidly acted to reduce ESR and CRP levels. e RA
factor showed a signicant reduction.
Metadichol, as we have shown, is an inverse agonist of VDR, and all
inverse agonists block constitutive response. We have shown
Metadichol exhibits dual properties such as increasing insulin
secretion [21] and reducing insulin in patients with type 2 diabetes [1].
It is likely a Protean agonist, which can act both as positive and
negative agonists on the same receptor, depending on the degree of
constitutive activity that is present. If there is no constitutive activity,
the agonist would be an active agonist. When the constitutive activity
is present, the Protean agonist would be an inverse agonist [22].
Elevated levels of CRP and ESR are associated with disease severity
in RA [23]. Our results show that Metadichol has successfully lowered
both CRP and ESR for the RA patient. His RA factor has also
decreased rapidly. e more striking nding was the improvement in
bone density as seen in Figures 4-6.
Osteoporosis is a condition in which the bone mineral density
(BMD) is 2.5 standard deviations below that of a young healthy,
gender-matched group (T less than -2.5). Osteopenia is dened as
bone mineral density that is 1 to 2.5 standard deviations below that of
a healthy sex-matched population (T-score between -1 and 2.5). BMD
less than -2.5 and with bone fracture indicates severe osteoporosis.
Figures 1-3: e treatment results with Metadichol and the
improvement on his biomarkers are indicated.
Figure 4: Improvement in bone density.
According to International Society for Clinical Densitometry, the
WHO criteria for osteoporosis applies to postmenopausal and
perimenopausal females and men over 60 years [24]. For all other
patients, the Z-score should be used with a cut o the standard of more
than -2.0 [26].
Citation: Raghavan PR (2017) Rheumatoid Arthritis and Osteoporosis: A Case Study. J Arthritis 6: 240. doi:10.4172/2167-7921.1000240
Page 2 of 4
J Arthritis, an open access journal
ISSN:2167-7921
Volume 6 • Issue 3 • 1000240
Figure 5: e more striking nding was the improvement in bone
density.
Figure 6: e more striking nding was the improvement in bone
density.
Using the criteria mentioned above, at baseline, the patient had
osteoporosis in his right femur with an increased risk of fragility
fractures and in his le femur with an increased risk of fragility
fractures by a factor of six which is ve times more than normal. e
bone mineral density of his lumbar spine and right forearm was in the
normal range.
Aer treatment with Metadichol for 52 weeks, the bone mineral
density of femoral and right forearm was in the normal range. BMD of
the lumbar spine normalized at 52 weeks. ere is a denite
improvement when compared to his baseline BMD of femoral.
Metadichol treatment led to the lower levels of the important
inammation biomarkers and alleviated his pain and increased his
mobility. Today’s approach in drug research is a lock (drug target) and
a key (drug) Given the many side eects of drugs, and to overcome it
the search for high selective ligands has been the approach of the drug
discovery community, and that has proven to be cost and time
consuming without any tangible benets [25].
Many useful drugs act via modulation of multiple proteins rather
than single targets. Some protein kinase inhibitors like Student and
Gleevec, act on multiple signaling kinases.
Yıldırım et al. suggest that many keys open a lock rather than one
key to open many locks [26].Mitigating disease states may require a
drug to act via multiple pathways to be potent, because aecting
multiple biological networks is more important than single network.
Such an approach has been highlighted and advocated by Andrew
Hopkins [27].
Eective drugs act via modulation of multiple proteins rather than
single targets. Metadichol does just that.
It’s mode of action is by optimizing multiple activities and
balancing drug-like properties and eliminating undesirable o target
eects. e inverse/protean property exhibited by Metadichol leads to
many pathways. It modulates by targeting, VDR, as well as inhibition
of cytokines like TNF-alpha, MCP-1, PAI-1 and the endogenous
increase of Vitamin C levels which we have shown in our Rat studies
[1]. Given the range and breadth of actions of Metadichol the results
suggest that it mimics the eects of 1,25-dihydroxy Vitamin D3 but
without the toxic eect secondary to Calcemia that limited its use as a
pharmaceutical agent [28]. Metadichol is the rst example of a smart
molecule that can simultaneously modulate multiple targets which can
lead potentially to a successful treatment of many of these challenging
diseases [29-33].
More clinical studies with Metadichol are planned, and
hopefully, it will be lead to overcoming RA and in improving bone
density which is of great importance in aging populations. Metadichol
can be useful an anti- inammatory molecule and has been shown to
have toxicity at doses of up to 5000 mg/kg [34-36]. Metadichol can be
useful in treating chronic diseases like RA.
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Citation: Raghavan PR (2017) Rheumatoid Arthritis and Osteoporosis: A Case Study. J Arthritis 6: 240. doi:10.4172/2167-7921.1000240
Page 4 of 4
J Arthritis, an open access journal
ISSN:2167-7921
Volume 6 • Issue 3 • 1000240
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In the past, laboratory tests were considered of limited value in Crohn?s disease (CD). In the era of biologics, laboratory tests have become essential to evaluate the inflammatory burden of the disease (C-reactive protein, fecal calprotectin) since symptoms-based scores are subjective, to predict the response to pharmacological options and the risk of relapse, to discriminate CD from ulcerative colitis, to select candidates to anti-tumor necrosis factors [screening tests looking for hepatitis B virus and hepatitis C virus status and latent tuberculosis], to assess the risk of adverse events (testing for thiopurine metabolites and thiopurine-methyltransferase activity), and to personalize and optimize therapy (therapeutic drug monitoring). Pharmacogenetics, though presently confined to the assessment of thiopurineme methyltransferase polymorphisms and hematological toxicity associated with thiopurine treatment, is a promising field that will contribute to a better understanding of the molecular mechanisms of the variability in response to the drugs used in CD with the attempt to expand personalized care and precision medicine strategies.
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Background Metadichol (1,2) is a Nano emulsion of long-chain alcohols called policosanols which are found in many foods like rice, wheat, grapes, sugar cane, apple and many others (3). It acts on membrane receptors in cells throughout the body to stimulate the immune system and inhibit a variety of disease processes, including those that result in metabolic diseases such as diabetes, obesity and hypertension. Methods A 38-year-old male of middle eastern origin was diagnosed as diabetic after complaining of tiredness and bouts of hunger. He was not on any medication and chose to be treated with Metadichol @ 10 mg per day. Findings Metadichol helped to lower his fasting blood sugar level from 300 mg/dl to normal in 6 weeks. His HBA1C was reduced from 9.8% to 6.2% in 12 weeks. After 32 more months, his diabetic indicators remain normal. Interpretation Metadichol is safe and effective in controlling blood sugar and HbA1C levels in humans. Metadichol has been shown to bind to the vitamin D receptor (2) as an inverse agonist. However, it acts more like a protean agonist ligand (4) to increase or decrease activity depending on the system. Since Metadichol has no known negative side effects and consists of natural components of common foods, Metadichol has the potential to serve as a novel treatment for type 2 diabetes.
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This study aimed to evaluate the relationship between the 25-hydroxyvitamin D [25(OH)D] level and rheumatoid arthritis (RA) and the correlation between serum vitamin D level and RA activity. Methods We searched the PUBMED, EMBASE, and Cochrane databases and performed a meta-analysis examining the vitamin D level and prevalence of vitamin D deficiency in patients with RA compared to healthy controls and the correlation coefficients between the vitamin D level and disease activity score 28 (DAS28) in RA patients. Results Fifteen studies that included a total of 1,143 RA patients and 963 controls were available for this meta-analysis. The meta-analysis showed that the serum vitamin D level in the RA group was significantly lower than that in the control group (SMD=-0.608, 95% CI=-1.105-[-0.017], p=0.017). In addition, the prevalence of vitamin D deficiency was significantly higher in the RA group than in the control group (55.2% vs. 33.2%; OR = 2.460, 95% CI = 1.135-5.332, p=0.023). Thirteen studies evaluated the correlation between the vitamin D level and its activity in 924 RA patients. Meta-analysis showed a significant inverse correlation between the vitamin D level and DAS28 (Correlation coefficient =-0.278, 95% CI =-0.393-[-0.153], p=1.8 x 10⁻⁵). Conclusion Our meta-analysis demonstrates that serum vitamin D level is significantly low in patients with RA, vitamin D deficiency is prevalent in RA patients compared to controls, and the vitamin D level correlates inversely with RA activity. Our meta-analysis suggests that the vitamin D level is associated with susceptibility to RA and RA activity.
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Since the discovery of group-specific component and its polymorphism by Hirschfeld in 1959, research has put spotlight on this multifunctional transport protein (vitamin D binding protein, DBP). Besides the transport of vitamin D metabolites, DBP is a plasma glycoprotein with many important functions, including sequestration of actin, modulation of immune and inflammatory responses, binding of fatty acids, and control of bone development. A considerable DBP polymorphism has been described with a specific allele distribution in different geographic area. Multiple studies have shed light on the interesting relationship between polymorphisms of the DBP gene and the susceptibility to diseases. In this review, we give an overview of the multifunctional character of DBP and describe the clinical importance of DBP and its polymorphisms. Finally, we discuss the possibilities to use DBP as a novel therapeutic agent.