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Metadichol ® Induced High Levels of Vitamin C: Case Studies

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We recently reported that Metadichol ® [1] brings about a three to four-fold increase in Vitamin C levels in patients without the use of Vitamin C supplementation. In this study of 6 patients who experienced a 5-12 fold increase in plasma Vitamin C levels higher than 80-100 u mol/L level which is the highest reported to date by oral supplementation at high doses of Vitamin C. Metadichol improved in these patients TSH levels, normalized High Blood pressure, fasting glucose levels, reduced eosinophil count, high triglycerides, body fat reduction and increased bone mass, normalized sodium levels, reducing high insulin levels, increased creatinine output in urine and also reducing of Red Cell Distribution width %. Metadichol thus serves as a surrogate for Vitamin C at doses of 5 mg per day as opposed to mega doses that are currently used.
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Metadichol® Induced High Levels of Vitamin C: Case Studies
Raghavan PR*
Nanorx Inc. PO Box 131, Chappaqua, NY 10514, USA
*Corresponding author: Raghavan PR, Nanorx Inc. PO Box 131, Chappaqua, NY 10514, USA, Tel: 9146710224; E-mail: raghavan@nanorxinc.com
Received date: August 14, 2017; Accepted date: September 05, 2017; Published date: September 19, 2017
Copyright: © 2017 Raghavan PR. 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
We recently reported that Metadichol® [1] brings about a three to four-fold increase in Vitamin C levels in patients
without the use of Vitamin C supplementation. In this study of 6 patients who experienced a 5-12 fold increase in
plasma Vitamin C levels higher than 80-100 u mol/L level which is the highest reported to date by oral
supplementation at high doses of Vitamin C. Metadichol improved in these patients TSH levels, normalized High
Blood pressure, fasting glucose levels, reduced eosinophil count, high triglycerides, body fat reduction and
increased bone mass, normalized sodium levels, reducing high insulin levels, increased creatinine output in urine
and also reducing of Red Cell Distribution width %. Metadichol thus serves as a surrogate for Vitamin C at doses of
5 mg per day as opposed to mega doses that are currently used.
Keywords: Vitamin C; Dehydroascorbic acid; Metadichol; Nanolipid;
Long chain saturated alcohols; VDR; Inverse agonist; Glutathione;
RDW; TSH; yroid antibodies; Gulo; Pseudo genes; Bone density;
Asthma; Eosinophil count Vitamin E; G6PD; Glucose Transporters;
Nuclear receptors
Introduction
Vitamin C is a ubiquitous key nutrient. Humans do not have the
ability to produce and synthesize vitamin C in their bodies and must
obtain it from food sources. Vitamin C synthesis is not possible in
guinea pigs, monkeys, and apes. Humans lack the L-Gluconolactone
oxidase (GULO) enzyme that completes the last enzymatic step of
synthesis of vitamin C from glucose [2]. In the genome of humans and
that of the anthropoid primates, a non-functional gene is present. is
inability to synthesize vitamin C in primates is believed to have
occurred about 60 million years ago [3].
Vitamin C is essential to maintain a sensitive balance in the
functioning of the organs in the body. It participates in the: hydrolysis
of individual amino acids, the formation of collagen necessary for body
growth, tissue repair and wound healing, synthesis of the hormone
adrenaline (epinephrine) and the hydroxylation of anti-inammatory
steroids in the adrenal gland, iron and copper metabolism, and folic
acid metabolism. Vitamin C is related to the metabolism of the
vitamins A, E, Bl and B12 [4]. e concentrations of total ascorbic acid
reduced and oxidized forms of ascorbic acid decline with age [5].
A review of the health benets of vitamin C
e role of vitamin C in thyroid disease: Dubey et al. have
documented low levels of ascorbic acid in patients with
hyperthyroidism [6]. ese have been conrmed by Ademoglu et al.
[7] and Alicigüzel et al. [8] Kumar et al. described low levels of vitamin
C in hyperthyroidism, while at the same time lipid peroxides, glucose,
and HbA1C levels were elevated [9].
Vitamin C and hypertension: Some epidemiological studies have
shown a negative correlation between BP and vitamin C [10,11,12].
Vitamin C use as a supplement improves vascular function and reduces
blood pressure in both experimental models and patients Ascorbate
improves vasodilation, probably by increasing Nitric Oxide
bioavailability. Mullan et al. showed that chronic daily
supplementation with 500 mg oral ascorbic acid could lower blood
pressure and improve arterial stiness in patients with type 2 diabetes
(Figure 1).
Vitamin C and bone density: Low plasma levels of vitamin C leads
to scurvy, which, among other ailments, causes gingiva, bone pain, and
impaired wound healing. A review by Patrick et al [13] describes the
importance of vitamin C as it relates to maintenance of bone tissues.
Various epidemiological studies and animal models show that Vitamin
C has a positive on trabecular bone formation by inuencing the
expression of bone matrix genes in osteoblasts.
Vitamin C and metabolic syndrome: Pearson et al. have reviewed
the literature on Vitamin C and its and showed that adults with higher
vitamin C levels show lower weight, BMI and waist circumference, and
improved metabolic health biomarkers like HbA1c, insulin and
triglycerides, that are major risk for type 2 diabetes [14].
Vitamin C and Asthma: Asthma leads to inammation of the
airways. Oxidants are one of the important factors that damage the
airways. Vitamin C is a protective antioxidant of the airways and
decreasing airway eosinophils in asthma is an indicator improved
asthmatic conditions. Low levels of antioxidants lead to more severe
asthma [15]. One needs to take mega doses of vitamin C to be eective.
Typical dietary quantities and low supplemental doses do not work.
[16,17].
Oral and IV Vitamin C and Plasma levels
Vitamin C concentration is controlled by intestinal absorption,
tissue transport, and renal reabsorption [18]. With increasing oral
doses of vitamin C up to 1000 mg, Levine et al. showed that plasma
vitamin C concentration reaches a steady-state concentration (60 to 80
μ mol/L) in healthy young adults [19,20]. Once plasma ascorbic acid
levels reach saturation, additional vitamin C gets excreted in the urine
IV administration of vitamin C bypasses the intestines and high
concentrations of ascorbic acid are achievable in the plasma; over time.
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ISSN: 2376-1318
Vitamins & Minerals
Raghavan, Vitam Miner 2017, 6:4
DOI: 10.4172/2376-1318.1000169
Research Article OMICS International
Vitam Miner, an open access journal
ISSN: 2376-1318
Volume 6 • Issue 4 • 1000169
But renal excretion restores vitamin C to baseline plasma levels [21].
Recent clinical reports indicate that the role of high-dose intravenous
vitamin C therapy in cancer treatment could be useful [22].
e higher blood level of Vitamin C is associated with lower
mortality and morbidity in several chronic conditions [23].
Metabolism of vitamin C, including absorption and its uptake by
several cell types, is inhibited by increasing glucose concentration. e
glucose-ascorbate antagonism (GAA) theory [24] suggests elevated
glucose levels restrict vitamin C from entering cells. Dehydroascorbic
acid (DHAA) transport into cells was shown to be impaired by high
blood glucose level in most cell types including adipocytes,
erythrocytes, neutrophils, osteoblasts and smooth muscle cell [25,26].
Metadichol ® is a mixture of C-26, C-28 and C-30 straight chain
alcohols. It is analogous with Vitamin D which is a cyclic C-27 alcohol.
e generic name is Policosanol. Metadichol is a Nano formulation of
these with a particle size of 53 nm. It is inverse agonist of Vitamin D
receptor (VDR). It is the only one of its kind known in literature today.
We have already documented that it increases Vitamin C levels leading
to improvement in disease conditions as we show in case Studies
below.
Figure 1: Patent No 1: F-61, diabetic, dyslipidemic for 5 years.
Treated with Metadichol 5 mg per day.
Methods and Objective
Non-randomized, Open study of 6 patients with various morbidities
with a below normal Vitamin C at baseline study on ecacy of
improved Vitamin C levels on various biomarkers with use of
Metadichol @ 5 mg per day for 90 days. One patient was followed for
an additional 90 days .
e patient information sheet detailed the procedures involved in
the study (aims, methodology. potential risks, anticipated benets) and
the investigator explained these to each patient. e patient signed the
consent form to indicate that the information had been explained and
understood. e patient was then allowed time to consider the
information presented before signing and dating the informed consent
form to indicate that they fully understood the information and
willingly volunteered to participate in the study. e patient was given
a copy of the informed consent form for their information. e
original copy of the informed consent was kept in a condential le in
the Investigators center records. Criteria for exclusion from the study
included pregnant or lactating females any serious and or uncontrolled
medical conditions interfering with the study or placing the patient at
unacceptable risk. Only patients who fullled all the inclusion criteria
and did not meet any of the exclusion criteria were enrolled into the
study .
Figure 2: Patient No 2. F-43, type 2 diabetic. Diagnosed at age 37.
Treated with Metadichol at 5 mg per day.
Subjects aged 18 years of age Various medical conditions received.
Metadichol at 5 mg per day orally Subject visits were scheduled at
Baseline/Day O (Visit 1). at Day 30 (Visit 2), Day 60 (Visit 3), and Day
90 (Visit 4) End of the Study. All visit occurred within Follow up visit
day+6 days. e study population consisted of male or non-pregnant
female patients aged 18 years of age with a previously diagnosed
medical conditions. All patients provided written informed consent to
participate in the study prior to being screened.
Citation: Raghavan PR (2017) Metadichol® Induced High Levels of Vitamin C: Case Studies. Vitam Miner 6: 169. doi:
10.4172/2376-1318.1000169
Page 2 of 5
Vitam Miner, an open access journal
ISSN: 2376-1318
Volume 6 • Issue 4 • 1000169
Figure 3: Patient No 3F-51. Co-morbidities Asthma and
Hypothyroidism. Metadichol treatment at 5 mg per day.
Figure 4: Patient No 4; M-44. Hypothyroid for past 5 years.
Metadichol treatment at 5 mg per day.
Results and Discussion
e results shown involved patients with a wide variety of disease
symptoms. e common theme is that in all the cases, there was a
signicant increase of Vitamin C, 3 to 11 times, that led to normalizing
key biomarkers for each patient. We have already shown how
Metadichol aects various diseases. Including Type 2 diabetes [27],
decreasing RDW [28], controlling of diastolic and systolic pressure,
[29].
Figure 5: Patient No 5M-50. Hypertension and elevated bilirubin
levels. Metadichol treatment at 5 mg per day.
e role of Vitamin D in thyroid related diseases is well known, and
the effect of, Metadichol on thyroid given its binding to VDR is not
surprising [35].
e actions of Metadichol binding to VDR leads to a proposed
pathway which eciently recycles Vitamin C (Figure 7).
In addition to serving as a substitute for Vitamin D, Metadichol is
also behaving as a Vitamin C substitute. It is possible to envision that
increased Vitamin C levels and VDR binding leads to a synergism
operating through multiple pathways to bring about homeostasis.
Complex diseases need drugs acting on distinct targets, which are part
of a network regulating various physiological responses. Metadichol is
exhibiting a poly pharmacological phenomenon by acting on multiple
targets pertaining to multiple disease pathways [36].
Citation: Raghavan PR (2017) Metadichol® Induced High Levels of Vitamin C: Case Studies. Vitam Miner 6: 169. doi:
10.4172/2376-1318.1000169
Page 3 of 5
Vitam Miner, an open access journal
ISSN: 2376-1318
Volume 6 • Issue 4 • 1000169
Figure 6: Patient NO 6; F-58, Hypertensive and low sodium
Metadichol treatment at 5 mg per day.
Figure 7: e actions of Metadichol binding to VDR leads to a
proposed pathway which eciently recycles Vitamin C.
Conclusion
All the main immune system cell lines function reaches peak
performance levels when there are adequate vitamin C levels in
plasma. Vitamin C depletion leads to inammation or infection [37].
is is why blood levels of vitamin C drop during times of disease or
infection. ere is a need to keep Vitamin C levels higher than what is
achievable by oral dosing. At normal levels of Vitamin C, one does not
see the eects that are seen when one reaches higher levels of Vitamin
C as observed in plasma with Metadichol. IV infusion of Vitamin C
does allow for higher levels to be reached, but that is not a practical
solution and is more useful in life threatening illnesses. Metadichol by
binding to VDR could serve as a useful surrogate of Vitamin C a
leading to in leading to higher levels in plasma and rectifying diseases.
References
1. Raghavan PR (2017) Metadichol ® and Vitamin C Increase In Vivo, an
Open-Label Study. Vitam Miner 6: 163.
2. Nobile S, Woodhill JM (1981) Vitamin C: the mysterious redox-system a
trigger of life? MTP Press; Lancaster, Boston, pp: 1-185.
3. Kagawa Y (2009) Human Specic Vitamin C Metabolism and Xenobiotic
Polymorphism: e Optimal Nutrition. In: Kucharski H, Zajac J (eds.)
Nova Science Publishers, Inc, pp: 45-85.
4. Levy T (2002) Vitamin C, Infectious Diseases, and toxins: Curing the
Incurable. Xlibris Corp, pp: 11-447.
5. Sasaki R, Tohoku J (1983) Inuences of sex and age on serum ascorbic
acid. J Exp Med 140: 97-104.
6. Dubey SS, Singh RP, Udupa KN (1977) Ascorbic acid status of
hyperthyroid patients. Indian J Med Res 65: 865-870.
7. Ademoglu E (1998) e eect of methimazole on the oxidant and
antioxidant system in patients with hyperthyroidism. Pharmacol Res 38:
93-96.
8. Aicigüzel (2001) Erythrocyte, plasma, and serum antioxidant activities in
untreated toxic multinodular goiter patients. Free Radic Biol Med. 30:
665-670.
9. Mohan Kumar KM (2004) Possible link between glycated hemoglobin
and lipid peroxidation in hyperthyroidism. Clin Chim Acta 342: 187-192.
10. Duy SJ, Gokce N, Holbrook M, Liza M, Elizabeth S, et al. (2001) Eect
of ascorbic acid treatment on conduit vessel endothelial dysfunction in
patients with hypertension. Am J Physiol Heart Circ Physiol 280:
528-534.
11. Duy SJ (1999) Treatment of hypertension with ascorbic acid. Lancet,
354: 2048-2049.
12. Rodrigo R, Prat H, Passalacqua W, Araya J, Guichard C, et al. (2007)
Relationship between oxidative stress and essential hypertension.
Hypertens Res 30: 1159-1167.
13. Mullen BA, Young IS, Fee H, McCance DR (2002) Ascorbic Acid Reduces
Blood Pressure and Arterial Stiness in Type 2 Diabetes. Hypertension
40: 804-809.
14. Aghajanian P (2015) J Bone Miner Res 30: 1945-1955.
15. Nasser M, Khan N, Khalid M, Omar S, Attas A, et al. (2013) Selected
Dietary Nutrients and the Prevalence of Metabolic Syndrome in Adult
Males and Females in Saudi Arabia: A Pilot Study. Nutrients 5:
4587-4604.
16. Misso NL, Wildhaber J, Ray S, Vally H, ompson PJ (2005) Plasma
concentrations of dietary and non-dietary antioxidants are low in severe
asthma. Eur Respir J 26: 257-264.
17. Harik-Khan RI, Muller DC, Wise RA (2004) Serum vitamin levels and the
risk of asthma in children. Am J Epidemiol 159: 351-357.
18. Levine M, Padayatty SJ, Espey MG (2011) Vitamin C: a concentration-
function approach yields pharmacology and therapeutic discoveries. Adv
Nutr 2: 78-88.
19. Levine M (1996) Vitamin C pharmacokinetics in healthy volunteers:
evidence for a recommended dietary allowance. Proc Natl Acad Sci 93:
3704-3709.
20. Levine M, Wang Y, Padayatty SJ, Morrow J (2001) A new recommended
dietary allowance of vitamin C for healthy young women. Proc Natl Acad
Sci 98: 9842-9846.
21. Padayatty SJ, Sun H, Wan Y, Hugh D, Hewitt S, et al. (2004) Vitamin C
pharmacokinetics: implications for oral and intravenous use. Ann Intern
Med 140: 533-537.
Citation: Raghavan PR (2017) Metadichol® Induced High Levels of Vitamin C: Case Studies. Vitam Miner 6: 169. doi:
10.4172/2376-1318.1000169
Page 4 of 5
Vitam Miner, an open access journal
ISSN: 2376-1318
Volume 6 • Issue 4 • 1000169
22. Padayatty SJ, Sun H, Wan Y, Hugh D, Hewitt S, et al. (2006) Intravenously
administered vitamin C as cancer therapy: three cases. CMAJ: Canadian
Medical Association 174: 937-942.
23. Clemens Z, Csaba T (2016) Vitamin C and Disease; Insights from the
Evolutionary Perspective, Journal of Evolution and Health 1: 13.
24. Hamel EE, Santisteban GA, Ely JT (1986) Hyperglycemia and
reproductive defects in non-diabetic gravidas: a mouse model test of a
new theory. Life Sci 39: 1425-1428.
25. Malo C, Wilson JX (2000) Glucose modulates vitamin C transport in
adult human small intestinal brush border membrane vesicles. J Nutr 130:
63-69.
26. Wilson JX (2005) Regulation of vitamin C transport. Annu Rev Nutr 25:
105-125.
27. Raghavan PR (2106) Metadichol and Type 2 Diabetes A case report.
Journal of the Science of Healing Outcomes 32: 5-10.
28. Raghavan PR (2017) Metadichol ® and Red Cell Distribution Width
(RDW) in CKD patients. J Stem Cell Res er 7: 392.
29. Raghavan PR (2017) Systolic, and Diastolic BP Control in Metabolic
Syndrome Patients with Metadichol® a Novel Nano Emulsion Lipid. J
Cardiol & Cardiovasc er 5: 555660.
30. Raghavan PR (2017) Metadichol® and MRSA Infections: A Case Report, J
Infect Dis er 5: 2.
31. Raghavan PR US patents, 9.722.093, 9,034,383 and 9,006.292.
32. Raghavan PR (2016) In vitro Inhibition of Zika Virus by Metadichol®. A
Novel Nano Emulsion Lipid, J Immunol Tech Infect Dis 5: 4.
33. Raghavan PR (2016) Inhibition of Dengue and other enveloped viruses by
Metadichol®, a novel Nano emulsion Lipid, Journal of the of Healing
Outcomes 31: 19-25.
34. Chuan Fan, eresa T (1940) Eect of Vitamin C on Creatine and
Creatinine Metabolism. Exp Bio Medi 45: 90-92.
35. Isabelle C (2012) e Vitamin D Receptor in yroid Development and
Function. Eur yroid J 1: 168-175.
36. Hopkins AL (2007) Network pharmacology. Nat Biotechnol 25:
1110-1111.
37. Pavlovic V (2010) A short overview of vitamin C and selected cells of the
immune system. Cent Eur J Med 8: 1-10.
Citation: Raghavan PR (2017) Metadichol® Induced High Levels of Vitamin C: Case Studies. Vitam Miner 6: 169. doi:
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... Moreover, the newly characterized hydroxylase enzymes, which regulate the activity of hypoxiainducible factor gene transcription and cell signalling of immune cells, need vitamin C as a cofactor for optimal activity [55][56][57]. Metadichol administration increases vitamin C levels endogenously by recycling vitamin C and produces levels not reached by oral intake, and those reached bring about changes in improving diverse biomarkers [58][59][60]. ...
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Background New pathogenic virus outbreaks, occurring with increasing regularity, are leading us to explore novel approaches, which will reduce the reliance on time-consuming vaccine modes to halt the outbreaks. The requirement is to find a universal approach to disarm any new and as yet unknown viruses as they appear. A promising approach could be targeting lipid membranes, which are common to all viruses and bacteria.The ongoing pandemic of severe acute respiratory syndrome-coronavirus 2 (SARS-COV-2) has reaffirmed the importance of interactions between components of the host cell plasma membrane and the virus envelope as a critical mechanism of infection. Metadichol®, a nano lipid emulsion, has been examined and shown to be a strong candidate to help stop the proliferation of SARS-COV-2.Naturally derived substances, such as long-chain saturated lipid alcohols, reduce the infectivity of various types of viruses, including coronaviruses such as SARS-COV-2, by modifying lipid-dependent attachment to human host cells. SARS-COV-2 uses the receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. Methods Metadichol was tested against TMPRSS2 ana ACE2 invitro using commercial available kits. Also it was tested against the live virus in Caco2 cells to test for inhibition of viral replication of SARS-COV-2.ResultsMetadichol®, a nano lipid formulation of long-chain alcohols, has been shown to inhibit TMPRSS2 (EC50 96 ng/ml). Compared to the inhibitor camostat mesylate (EC50 26000 ng/ml), it is 270 times more potent. Additionally, Metadichol® is also a weak inhibitor of ACE2 at 31 µg/ml. Further a live virus assay in Caco2 cells, Metadichol® inhibited SARS-CoV-2 replication with an EC90 of 0.16 µg/ml.Conclusions Metadichol inhibits SARS-COV-2 virus and since it a non toxic molecule can be easily tested in humans and as it has LD 50 of over 5000 mg/kilo and could help mitigate the crisis facing the world today.
... Moreover, the newly characterized hydroxylase enzymes, which regulate the activity of hypoxia-inducible factor gene transcription and cell signalling of immune cells, need vitamin C as a cofactor for optimal activity [56][57][58] . Metadichol administration increases vitamin C levels endogenously by recycling vitamin C and produces levels not reached by oral intake, and those reached bring about changes in improving diverse biomarkers [59][60][61] . ...
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Full-text available
New pathogenic virus outbreaks, occurring with increasing regularity, are leading us to explore novel approaches, which will reduce the reliance on time-consuming vaccine modes to halt the outbreaks. The requirement is to find a universal approach to disarm any new and as yet unknown viruses as they appear. A promising approach could be targeting lipid membranes, which are common to all viruses and bacteria. The ongoing pandemic of severe acute respiratory syndrome-coronavirus 2 (SARS-COV-2) has reaffirmed the importance of interactions between components of the host cell plasma membrane and the virus envelope as a critical mechanism of infection. Metadichol®, a nano lipid emulsion, has been examined and shown to be a strong candidate to help stop the proliferation of SARS-COV-2. Naturally derived substances, such as long-chain saturated lipid alcohols, reduce the infectivity of various types of viruses, including coronaviruses such as SARS-COV-2, by modifying lipid-dependent attachment to human host cells. SARS-COV-2 uses the receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. Metadichol®, a nano lipid formulation of long-chain alcohols, has been shown to inhibit TMPRSS2 (EC50 96 ng/ml). Compared to the inhibitor camostat mesylate (EC50 26000 ng/ml), it is 270 times more potent. Additionally, Metadichol® is also a extremely weak inhibitor of ACE2 at 31 µg/ml. Further a live virus assay in Caco2 cells, Metadichol® inhibited SARS-CoV-2 replication with an EC90 of 0.16 µg/ml.
... Vitamin C is also required as a cofactor for the optimal activity of newly characterized hydroxylase enzymes, which regulate the activity, gene transcription, and signaling of hypoxia-inducible factors in immune cells [58][59][60]. Of note, studies have demonstrated that Metadichol administration increases the endogenous vitamin C levels by recycling it to levels that are not achieved by oral intake, and these levels bring about changes in improving diverse biomarkers [61][62][63]. ...
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New pathogenic virus outbreaks, occurring with increasing regularity, are leading us to explore novel approaches, which will reduce the reliance on time-consuming vaccine modes to halt the outbreaks. The requirement is to find a universal approach to disarm any new and as yet unknown viruses as they appear. A promising approach could be targeting lipid membranes, which are common to all viruses and bacteria. The ongoing pandemic of severe acute respiratory syndrome-coronavirus 2 (SARS-COV-2) has reaffirmed the importance of interactions between components of the host cell plasma membrane and the virus envelope as a critical mechanism of infection. Metadichol®, a nano lipid emulsion, has been examined and shown to be a strong candidate to help stop the proliferation of SARS-COV-2. Naturally derived substances, such as long-chain saturated lipid alcohols, reduce the infectivity of various types of viruses, including coronaviruses such as SARS-COV-2, by modifying lipid-dependent attachment to human host cells. SARS-COV-2 uses the receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. Metadichol®, a nano lipid formulation of long-chain alcohols, has been shown to inhibit TMPRSS2 (EC50 96 ng/ml). Compared to the inhibitor camostat mesylate (EC50 26000 ng/ml), it is 270 times more potent. Additionally, Metadichol® is also a weak inhibitor of ACE2 at 31 µg/ml. Further a live virus assay in Caco2 cells, Metadichol® inhibited SARS-CoV-2 replication with an EC90 of 0.16 µg/ml. Keywords: Coronavirus, SARS-COV-2, COVID-19, ACE2, TMPRSS2, VDR, Metadichol
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Increasing outbreaks of new pathogenic viruses have promoted the exploration of novel alternatives to time-consuming vaccines. Thus, it is necessary to develop a universal approach to halt the spread of new and unknown viruses as they are discovered. One such promising approach is to target lipid membranes, which are common to all viruses and bacteria. The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has reaffirmed the importance of interactions between the virus envelope and the host cell plasma membrane as a critical mechanism of infection. Metadichol®, a nanolipid emulsion of long-chain alcohols, has been demonstrated as a strong candidate that inhibits the proliferation of SARS-CoV-2. Naturally derived substances, such as long-chain saturated lipid alcohols, reduce viral infectivity, including that of coronaviruses (such as SARS-CoV-2) by modifying their lipid-dependent attachment mechanism to human host cells. The receptor ACE2 mediates the entry of SARS-CoV-2 into the host cells, whereas the serine protease TMPRSS2 primes the viral S protein. In this study, Metadichol® was found to be 270 times more potent an inhibitor of TMPRSS2 (EC50=96 ng/mL) than camostat mesylate (EC50=26000 ng/mL). Additionally, it inhibits ACE with an EC50 of 71 ng/mL, but it is a very weak inhibitor of ACE2 at an EC50 of 31 μg/mL. Furthermore, the live viral assay performed in Caco-2 cells revealed that Metadichol® inhibits SARS-CoV-2 replication at an EC90 of 0.16 μg/mL. Moreover, Metadichol® had an EC90 of 0.00037 μM, making it 2081 and 3371 times more potent than remdesivir (EC50=0.77 μM) and chloroquine (EC50=1.14 μM), respectively.
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Purpose: Currently, several disorders including burns, trauma, excisional and diabetic wounds, and bedsores threaten the human health. Application of mesenchymal stem cells (MSCs) is recommended for treatment of skin disorders. However, because of oxidative stress and inflammation after skin injury, survival of transplanted MSCs is low which in turn negatively affects the efficiency of the MSCs-based therapy. In an attempt to address the aforementioned challenge and introducing a novel potential therapeutic strategy, we employed combination therapy by Lipocalin (Lcn2)-engineered MSCs and a Metadichol (an inverse agonist of vitamin D receptor (VDR)) nanogel in a rat model of excisional wound. Methods: First, Human umbilical cord MSCs (hUC-MSCs) was transfected by a recombinant plasmid encoding Lipocalin 2 (Lcn2) gene. Next, a combination of Metadichol nanogel and the engineered MSCs was co-applied on wound in rat model of excision injury. Finally the improvement of wound healing in experimental groups was evaluated by photography and histological assessments (hematoxylin and eosin staining). Results: Our findings revealed that the repair rate was higher in the group received combination therapy comparing to control groups. Notably, Metadichol+Lcn2-MSCs showed significantly higher wound contraction rate compared to control group at all time points (p value< 0.001). Furthermore, wound repair rate was 95% 14 days after surgery, and 100% after 21 days in the treatment groups. Our results also revealed that the combination therapy improved and accelerated the wound healing process. Conclusion: Our findings suggest a novel potential therapeutic strategy i.e. Lcn2-engineered MSCs and Metadichol for wound healing. However, further preclinical and clinical studies are required.
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New pathogenic virus outbreaks, occurring with increasing regularity, are leading us to explore novel approaches, which will reduce the reliance on time-consuming vaccine modes to halt the outbreaks. The requirement is to find a universal approach to disarm any new and as yet unknown viruses as they appear. A promising approach could be targeting lipid membranes, which are common to all viruses and bacteria. The ongoing pandemic of severe acute respiratory syndrome-coronavirus 2 (SARS-COV-2) has reaffirmed the importance of interactions between components of the host cell plasma membrane and the virus envelope as a critical mechanism of infection. Metadichol®, a nano lipid emulsion, has been examined and shown to be a strong candidate to help stop the proliferation of SARS-COV-2. Naturally derived substances, such as long-chain saturated lipid alcohols, reduce the infectivity of various types of viruses, including coronaviruses such as SARS-COV-2, by modifying lipid-dependent attachment to human host cells. SARS-COV-2 uses the receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. Metadichol®, a nano lipid formulation of long-chain alcohols, has been shown to inhibit TMPRSS2 (EC50 96 ng/ml). Compared to the inhibitor camostat mesylate (EC50 26000 ng/ml), it is 270 times more potent. Additionally, Metadichol® is also a extremely weak inhibitor of ACE2 at 31 µg/ml. Further a live virus assay in Caco2 cells, Metadichol® inhibited SARS-CoV-2 replication with an EC90 of 0.16 µg/ml.
Preprint
Full-text available
New pathogenic virus outbreaks, occurring with increasing regularity, are leading us to explore novel approaches, which will reduce the reliance on time-consuming vaccine modes to halt the outbreaks. The requirement is to find a universal approach to disarm any new and as yet unknown viruses as they appear. A promising approach could be targeting lipid membranes, which are common to all viruses and bacteria. The ongoing pandemic of severe acute respiratory syndrome-coronavirus 2 (SARS-COV-2) has reaffirmed the importance of interactions between components of the host cell plasma membrane and the virus envelope as a critical mechanism of infection. Metadichol®, a nano lipid emulsion, has been examined and shown to be a strong candidate to help stop the proliferation of SARS-COV-2. Naturally derived substances, such as long-chain saturated lipid alcohols, reduce the infectivity of various types of viruses, including coronaviruses such as SARS-COV-2, by modifying lipid-dependent attachment to human host cells. SARS-COV-2 uses the receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. Metadichol®, a nano lipid formulation of long-chain alcohols, has been shown to inhibit TMPRSS2 (EC50 96 ng/ml). Compared to the inhibitor camostat mesylate (EC50 26000 ng/ml), it is 270 times more potent. Additionally, Metadichol® is also a weak inhibitor of ACE2 at 31 µg/ml. Further a live virus assay in Caco2 cells, Metadichol® inhibited SARS-CoV-2 replication with an EC90 of 0.16 µg/ml.
Preprint
Full-text available
New pathogenic virus outbreaks, occurring with increasing regularity, are leading us to explore novel approaches, which will reduce the reliance on time-consuming vaccine modes to halt the outbreaks. The requirement is to find a universal approach to disarm any new and as yet unknown viruses as they appear. A promising approach could be targeting lipid membranes, which are common to all viruses and bacteria. The ongoing pandemic of severe acute respiratory syndrome-coronavirus 2 (SARS-COV-2) has reaffirmed the importance of interactions between components of the host cell plasma membrane and the virus envelope as a critical mechanism of infection. Metadichol®, a nano lipid emulsion, has been examined and shown to be a strong candidate to help stop the proliferation of SARS-COV-2. Naturally derived substances, such as long-chain saturated lipid alcohols, reduce the infectivity of various types of viruses, including coronaviruses such as SARS-COV-2, by modifying lipid-dependent attachment to human host cells. SARS-COV-2 uses the receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. Metadichol®, a nano lipid formulation of long-chain alcohols, has been shown to inhibit TMPRSS2 (EC50 96 ng/ml). Compared to the inhibitor camostat mesylate (EC50 26000 ng/ml), it is 270 times more potent. Additionally, Metadichol® is also a weak inhibitor of ACE2 at 31 µg/ml. Further a live virus assay in Caco2 cells, Metadichol® inhibited SARS-CoV-2 replication with an EC90 of 0.16 µg/ml.
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Metadichol® a nano formulation and mixture of long chain alcohols that is present in many foods like rice and sugar cane. It is derived from the waste of the sugar cane industry and therefore, it is a renewable resource. Most of the clinical data in the literature are from non-nano formulations either in a tablet or a capsule form which has not shown any efficacy. Given its safety profile, we carried out a small open label pilot study on 14 diabetic patients with hypertension. These patients had co-morbidities such as dyslipidemia, obesity and hypertension, but were not on any hypertensive medication. In this open label study, we treated the patients with 20mg of Metadichol per day for 60 weeks. The results showed that it is possible to bring about improvements in Systolic and Diastolic blood pressure in addition to CRP, VLDL, HDL, Triglycerides, waist circumference reduction, and reduction in insulin resistance. Interestingly, the average Vitamin C level for this study group also doubled. This study showed a vast improvement over existing therapies and with no reported side effects (minor or major).
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Vitamin C, also known as ascorbic acid, is a water-soluble antioxidant. Today we meet our requirements of vitamin C through consumption of fruits and vegetables or by supplementation. Homo sapiens cannot produce vitamin C like many other species that can convert glucose to vitamin C. The gene for enzyme production is dormant in humans. The gene, GULO, that we all carry converts glucose to Vitamin C. in other species but not in humans and primates. The open-label study showed Metadichol ® raised levels of vitamin C by 3 fold, endogenously without supplementation of Vitamin C. Possible mechanisms for the increased Vitamin C levels through antioxidant pathways are presented. Metadichol ® [1] is a nano-formulation of long chain alcohols derived from sugar cane. In addition to increased Vitamin C levels reduction in Potassium and uric acid, and decreased blood pressure and improvement in quality of life issues were also observed.
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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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The role of vitamin C at the physiological and cellular levels is indisputable. In line with this, blood level of vitamin C is inversely related to disease parameters such as risk of cancer, cardiovascular disease and mortality in prospective cohort and correlational studies. At the same time, adequately powered clinical intervention studies consistently provide no evidence for a beneficial effect of supplementing vitamin C. Here we provide a framework to resolve this apparent conflict. Besides providing an overview of the widely-known facts regarding vitamin C, we review evidence that are of potential relevance but are seldomly mentioned in the context of vitamin C. We invoke the glucose-ascorbate antagonism (GAA) theory which predicts that as a consequence of their molecular similarity glucose hinders the entry of vitamin C into cells. Integrating data coming from research at the cellular level, those from clinical, anthropological and dietary studies, in the present hypothesis paper we propose an evolutionary framework which may synthesize currently available data in the relation of vitamin C and disease. We put forward that instead of taking vitamin C as a supplement, an evolutionary adapted human diet based on meat, fat and offal would provide enough vitamin C to cover physiological needs and to ward off diseases associated with vitamin C deficiency.
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Vitamin D is known to modulate thyroid neoplastic and autoimmune disease. We investigated the role of the vitamin D receptor (VDR) in normal thyroid development and function (thyrocytes and C cells). The thyroid phenotype of VDR knockout mice was studied in comparison to wild-type controls. The mice were fed a normal diet or a calcium-rich diet to circumvent effects induced by hypocalcemia. Thyroid morphology was unaltered in VDR knockout mice. Also, expression of different parameters of thyrocyte function was comparable (immunohistochemistry). C cell physiology was, however, affected in the absence of the VDR, resulting in increased thyroidal calcitonin expression (immunohistochemistry), paralleled by increased serum calcitonin levels, but only in normocalcemic mice. To study a possible effect of vitamin D status on basal calcitonin levels in humans, serum calcitonin concentrations were compared between vitamin D-deficient and -sufficient patients (serum 25-OH vitamin D3 ≤10 and ≥40 ng/ml, respectively), but no difference was observed. In mice, the VDR is redundant for normal thyrocyte function, but not for C cell function, where it mediates the negative control of calcitonin by 1,25-dihydroxyvitamin D3. In patients, vitamin D status does not affect basal serum calcitonin levels. A study in healthy individuals is needed to confirm these findings.
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Metadichol ® [1] is a Nanoemulsion 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 have a ubiquitous presence in cells and tissues of the body to stimulate the immune system and inhibit a variety of disease processes, resulting from viral, bacterial and parasitic infections. Infectious agents can cause disease by avoiding normal host defense mechanisms or by subverting them to promote their replication. They do so by blocking VDR receptor that is responsible for innate immunity, and this suppression of the immune response leads to persistent infections. We present a case study of a patient who had acquired MRSA infections and how Metadichol ® by its actions on the VDR has resolved the problem of this deadly disease without any side effects.
Article
The biomedical significance of human vitamin C (VC) metabolism is reviewed in the light of polymorphisms in xenobiotic enzymes deduced from genetic, biochemical, and epidemiological results to estimate optimal nutrition. VC comprises both ascorbic acid (AsA) and dehydroascorbic acid (DAsA). AsA is oxidized to DAsA via short-lived monodehydroascorbate radicals in a series of xenobiotic reactions and by reactive oxygen species (ROS). DAsA is reversibly reduced by glutaredoxin, but is also irreversibly hydrolyzed into 2,3-diketo-L-gulonate by dehydroascorbatase [EC 3.1.1.17] and non-enzymatic reactions. VC is a cofactor in reactions catalyzed by Cu+-dependent monooxygenases [EC 1.13.12.-] and Fe2+-dependent dioxygenases [EC 1.13.11.-]. VC plays a protective role against oxidative stress by ROS and xenobiotics, via monodehydroascorbate radicals. The Vitamin Society of Japan has re-evaluated old data because of the development of life science. The recommended dietary allowance (RDA) of VC is 100 mg/day for adults in Japan to prevent scurvy. RDA is defined as EAR+2SD, i.e. estimated average requirement (EAR) and the standard deviation (SD) obtained by short-term depletion-repletion studies. However, based on VC synthetic rates in rat, Pauling proposed that the optimum intake is 2.3 g/day. This is the problem of RDA vs. optimal nutrition. Optimal nutrition is wider in scope than RDA that covers genetic polymorphisms, long-term health outcome during the lifespan, and xenobiotics. Humans (VC auxotrophs) have relatively low plasma AsA levels and high serum uric acid levels compared to most VC-synthesizing mammals (VC autotrophs) due to gene defects in L-gulonolactone oxidase (GLO [EC 1.1.3.8]) and uricase (urate oxidase) [EC 1.7.3.3], respectively. Extrapolation of metabolic data of VC autotrophs to estimate human optimal nutrition is limited because of the compensatory mechanism for the GLO defect in VC auxotrophs, including DAsA transport by GLUT1, and specific mutations in uricase and dehydroascorbatase. Beneficial effects of long-term VC supplementation remain controversial, perhaps because of 1. genetic heterogeneity in study populations, and 2. the balance of antioxidant and pro-oxidant activities of VC depending on the xenobiotic conditions. Thus, in addition to the biochemical studies on AsA and DAsA, human genetic analysis on VC-loading experiments and epidemiological survey are needed. There are marked interindividual differences (coefficient of variation >45%) in the metabolism of VC. This difference is evident during oral loading with 1 mmol AsA or DAsA in subjects consuming a diet low in VC (less than 5 mg/day) for 3 days before loading in the cross-over experiment. Since tubular maximum reabsorption of AsA (TmAsA) and glomerular filtration rate (GFR) are similar among subjects, degradation steps of VC may be involved in the personal difference. The metabolisms of three most important water-soluble antioxidants in mammals i.e. VC, urate and glutathione are different in humans and other animals. The effects of polymorphism A313G (Ile105Val) in the gene for glutathione S-transferase P1 (GSTP1) [EC 2.5.1.18], one of the most active xenobiotic enzymes in the second phase of detoxification, on human VC metabolism were thus studied. In an epidemiologic survey of Mongolians (n = 164) with very low VC intake, serum VC concentration was only 28%, and the level of reactive oxygen metabolites was 128%, when compared with those in Japanese. The variant frequency of GSTP1 among Japanese subjects (n = 210) was AA, 71.0%; GA, 27.0% and GG, 1.9%. In Mongolian subjects (n = 93), it was AA, 62.4%; GA, 36.6%; and GG, 1.1%.In VC loading experiments, at 24 h after administration of 1 mmol of VC to young women (n = 17; age, 21.0 ± 1.1 y, glomerular filtration rate, GFR = 90 ml/min), total VC excretion (46.7 ± 18.1 mg) by AA homozygotes of GSTP1 was greater (p < 0.0069) than that (28.2 ± 14.0 mg) by GA heterozygotes. One hour after administration of VC, blood total VC levels were also significantly different (p < 0.0036) between the homozygotes and heterozygotes. The results of background experiments were as follows: (1) the VC level in 24-h urine after VC loading did not differ between the two orally administered C forms (AsA and DAsA); (2) VC excretion between 0 and 3 h after VC loading was significantly higher (p < 0.05) for DAsA, while those between 3 and 6, 6 and 9, 9 and 12, and 12 and 24 h after VC loading were significantly higher (p < 0.05 or p < 0.01) for AsA; and (3) blood VC concentrations and the increase in VC at 1 h after VC loading were significantly higher (p < 0.05 and p < 0.01, respectively) in the DAsA group than in the AsA group. The difference between AsA and DAsA dynamics in (2) and (3) may be explained by the sodium-dependent active transport of AsA by SVCT1 and 2, and passive transport of DAsA by glucose transporters (GLUTs) in the presence of glutathione. The large species differences in DAsA metabolism are partly explained by the low activity of human dehydroascorbatase, which has a unique structure, as deduced by X-ray crystallography, and a unique sequence of 299 amino acids. The anti-oxidant and anti-xenobiotic roles of monodehydroascorbate radicals both in vivo and in vitro are important. ROS are generated mainly in mitochondria but DAsA transported through GLUT1 into mitochondria is converted into AsA and prevents oxidative stress. Finally RDA and optimal nutrition are discussed from the standpoint of human specific metabolism of VC including prevention against ROS produced by exercise and pathological conditions.