Metadichol® and Vitamin C Increase In Vivo, an Open-Label Study

Abstract

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.

Full text

Metadichol® and Vitamin C Increase
In Vivo
, an Open-Label Study
Raghavan PR*
Nanorx Inc., Chappaqua, NY, USA
*Corresponding author: Raghavan PR, Nanorx Inc., Chappaqua, NY, USA, Tel: 9146710224; E-mail: raghavan@nanorxinc.com
Received date: July 01, 2017; Accepted date: July 07, 2017; Published date: July 14, 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
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.
Keywords: Vitamin C; Dehydroascorbic acid; Gulo; Pseudogenes;
Metadichol; Nano lipid; Long chain saturated alcohols; VDR; Inverse
agonist; Protean agonist; VDR, Glutathione; Lipoic acid; Coq-10;
Vitamin E; Vitamin C; NRF2; G6PD
Introduction
Vitamin C for treating scurvy was use was discovered by
Christopher Columbus’s sailors with fresh lime juice, during long sea
voyages. e sailors, of course, did not know the chemical formula
which Linus Pauling discovered in his laboratory. Pauling proclaimed
to the world that ascorbic acid if consumed in massive doses, is the
panacea for all human ills. Literature surveys suggest that ascorbate is
essential for the immune system to work eciently and strengthening
the immune system and can help those with impaired immunity [2-5].
Homo sapiens, monkeys, and a few other species do not produce
their own vitamin C. e rest of the animal kingdom synthesize their
own vitamin C. For animals that synthesize vitamin C it is a hormone,
not a dietary-acquired vitamin. Homo sapiens once made vitamin C in
the liver by the production of four enzymes which converted
circulating sugars into ascorbic acid (vitamin C). e rst three of the
four enzymes required to convert glucose (sugar) into ascorbic acid is
present in humans today, but the fourth, not found in humans is the
enzyme Gulo (gluconolactone oxidase) (Figure 1). A mutation at some
same point deactivated the gene for the synthesis of vitamin C and the
production of the fourth enzyme came to an end in humans [6].
Species that make their own vitamin C, live 8 to 10 times beyond their
age of physical maturity. Species without this ability reach only 3 to 4
times their age of physical maturity. Researchers believe the
reinstallation of the Gulo (gulonolactone oxidase) enzyme in humans
would extend the lifespan to hundreds of years [6].
Can gluconolactone oxidase gene somehow be reinserted into the
human genome? Guinea pigs, lacking gluconolactone oxidase, when
given this enzyme by injection, can live on a diet decient in vitamin C
[7]. Scientists have taken the gluconolactone oxidase DNA from rat
liver and successfully transplanted it into the tomato genome [8]. With
advances in gene therapy, the feasibility of inserting the gluconolactone
oxidase gene into the human genome has not been tried so far.
Figure 1: Glucose to Vitamin C pathway.
Supplementation of drinking water with vitamin C increased the
average life span of mice by as much as 20 percent [9]. Pauling
suggested humans supplement their diet continuously as a substitute to
what the liver would make as if the gene for the gluconolactone oxidase
enzyme were active [10]. Males who have higher blood serum levels of
vitamin C had lower levels of mortality [10]. Men and women ages 40
and above a 50-milligram increase in vitamin C consumption reduced
the death rate by 20 percent [11]. Vitamin C is an essential antioxidant
in overcoming the eects of aging. Vitamin C slows down telomeres
decline by 50 to 60 percent [12,13] (Table 1).
Vitamins & Minerals Raghavan, Vitam Miner 2017, 6:2
DOI: 10.4172/2376-1318.1000163
Research Article OMICS International
Vitam Miner, an open access journal
ISSN: 2376-1318
Volume 6 • Issue 2 • 1000163

Gender
Female Age
(Years) Male Age(Years)
N 17 14
Percentage 54.85 45.15
Minimum 31 32
Maximum 65 76
Mean 52 55.4
Std Deviation 10.58 11.78
Height (cm)
Minimum 142 150
Maximum 171 177
Mean 155.76 166
Std Deviation 7.24 7.57
Weight (Kg)
Minimum 52.8 59.7
Maximum 87 116.1
Mean 70.68 75.86
Std Deviation 10.16 15.03
BMI
Minimum 22.6 22.9
Maximum 35.3 37.1
Mean 29.1 27.37
Std Deviation 4.12 3.46
Table 1: Gender showing standard deviation results.
Humans who consume 300 milligrams of daily vitamin C appear to
reduce the risk of cataracts [13]. A 500-milligram daily dose of vitamin
C is seen to reduce blood pressure among hypertensive patients who
previously used prescription drugs [14].
A mouse and a 160-pound goat make about 275 and 13000 mg of
milligrams of vitamin C per day respectively. is correlates in humans
to 2,000-20,000 milligrams per day. e recommended dose today is
only about 90 milligrams of vitamin C a day for adults, but that' dose is
the minimum amount to prevent scurvy and promote general health,
but does not achieve optimal health and longevity [15].
To reach Plasma vitamin C concentration of 0.6-1 mg/dl one needs
a minimum of 1000 mg per day of Vitamin C. Less than 5% of US
population have plasma vitamin C level above the 0.6 mg/dl [16].
A study conducted by NIH investigators states that doses of
supplemental vitamin C above 200 milligrams daily are “nearly
completely excreted in urine.” Furthermore, the concentration of
vitamin C in blood plasma never exceeds much more than 0.6-1.3
mg/dl regardless of the of vitamin C consumed [17].
Two thousand milligrams of oral vitamin C produced 1.3 mg/dl in
plasma levels [18]. All the work reported so far deal with oral
consumption of Vitamin C, but increasing levels endogenously without
supplementation of vitamin C is rare. A recent study [19] showed that
using hydroxytyrosol, the main phenolic component of olive oil at 45
mg per day, allowed the endogenous levels to increase two-fold. e
impetus for this study was that policosanol, the main ingredient in
Metadichol, is present in olive oil [20]. We reasoned that Metadichol
should show similar eects. We now report that Metadichol raised
Vitamin C levels by 3 to 4 folds without any diet restrictions as was the
case in the hydroxytyrosol study.
Study
Primary objective
Non-randomized, open, single group, study to evaluate the safety
and ecacy of Metadichol in subjects with various medical conditions
to improve vitamin C levels from Day 0 to Day 90.
Secondary objective
To evaluate the safety of Metadichol.
is was a 90-day prospective, non-randomized, open, single-group
study. Subjects aged 18 yrs. of age with had on an average three co-
morbidities received Metadichol. Subject visits were scheduled at
baseline/day O (visit 1), day 30 (visit 2), day 60 (visit 3), and day 90
(visit 4). End of the study. All visits occurred within follow-up visit day
within plus /minus six days.
e study population consisted of male or non-pregnant female
patients aged 18 and over with diagnosed various diagnosed medical
conditions. All patients were provided written informed consent to
participate in the study before screening. Twenty enrolled and 27
completed as per protocol (Table 2).
Patient information Number
Enrolled 31
Completed 27
Per Protocol 27
Safety Population 31
Table 2: Patients list before screening test.
e patient information sheet contained procedures involved in the
study (aims, methodology. potential risks, anticipated benets) and
was explained these to each patient. Signed the consent form to from
each patient was obtained to indicate that the information had been
disclosed and understood. 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 investigator's
central records.
Criteria for exclusion from the study included pregnant or lactating
females any serious and 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. Each patient had on
an average three co-morbidities.
Citation: Raghavan PR (2017) Metadichol® and Vitamin C Increase In Vivo, an Open-Label Study. Vitam Miner 6: 163. doi:
10.4172/2376-1318.1000163
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Vitam Miner, an open access journal
ISSN: 2376-1318
Volume 6 • Issue 2 • 1000163

e primary ecacy endpoint
Improvement (change) in vitamin C levels at the end of day 90 as
compared to baseline safety evaluation.
Safety evaluation analysis of the following parameters: e type of
AE(s), the number of AE (s), the frequency of AE(s) and proportion of
patients with AE(s).
Physical examination.
Assessment of vital signs.
Safety Laboratory tests included complete blood count, liver
function tests, urea, creatinine electrolytes, and urine analysis.
Safety results
Metadichol was safe and tolerated, and this was conrmed by no
incidences of adverse events and good compliance.
No deaths, and or any side eects were seen or reported by patients
in this study.
Vital signs were found normal range during the study. ere were no
clinically signicant abnormal ndings at any of the visits. ere were
no abnormal clinical ndings at any of the visits.
Results
e results of this study demonstrate that Metadichol has a better
ecacy prole as evidenced in the changes (improvement) in the levels
of vitamin C (Figure 2). Lymphocyte, ESR, ACE (absolute Eosinophil
counts), potassium, and other biomarkers (Table 3). Metadichol, at the
end of day 90+6 days, is safe and well tolerated. Analysis of Variance
one way was carried out using JMP soware from SAS.
Figures 2-4: 2) Vitamin C; 3) Patients with Vitamin C; 4) Patient
with Low Vitamin C.
e increase in vitamin C levels was remarkable and statistically
signicant with values <0.00001 as shown in Table 4. Vitamin C levels
below 0.6 mg/dl are considered decient. Comparing patients with
vitamin C below 0.6 mg/dl (17 patients) and those above (10 patients)
the increase was remarkable as shown in Figures 3 and 4. Both sets of
patients reached similar levels 1.06-1.09 mg/dl. All patients were
interviewed at the end of their study, and every patient reported a
quality of life improvement and improvement in medical issues of
concern to them. Patient feedback and observations from the doctors
are summarized in Table 5.
Biomarkers Baseline Day 90
Vitamin C (mg/dl) 0.39 1.06
Potassium (mmol/L) 4.38 3.88
Uric acid (mg/dl) 6.23 4.71
ESR (mm/hr) 22.29 18.14
TSH (µlU/ml) 3.58 3.02
Systolic BP (mm Hg) 129.33 123.3
Diastolic BP (mm Hg) 82.27 79.57
Body Fat (%) 37.4 36.03
Bone Mass (%) 2.59 2.69
Muscle Mass (%) 42.71 44.4
Total Body fat (%) 43.77 41.88
Sodium (mEq/L) 135.6 140.1
HbA1C (%) 6.74 6.4
Mean plasma glucose (mg/dl) 146.6 136.88
Citation: Raghavan PR (2017) Metadichol® and Vitamin C Increase In Vivo, an Open-Label Study. Vitam Miner 6: 163. doi:
10.4172/2376-1318.1000163
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Vitam Miner, an open access journal
ISSN: 2376-1318
Volume 6 • Issue 2 • 1000163

Absolute Eisnophil Count (cmm) 390.9 349.9
WBC (thou/µL) 7.25 6.98
Hemoglobin (g/dl) 13.52 13.5
RBC (mil/µlL) 4.9 4.86
Mean plasma glucoe 146.6 136.88
SGPT (U/L) 34 30
SGOT (U/L) 20.45 21.07
Table 3: Biomarkers Baseline.
Baseline Day 90 Total
N 27 27 54
∑X 13.11 29.38 42.49
Mean 0.4856 1.0881 0.7869
∑X2 9.3313 36.7028 46.0341
Std.Dev. 0.3377 0.4267 0.4876
Result Details
Source SS df MS
Between-treatments 4.9021 1 4.9021
Within-Treatments 706987 52 0.1481
Total 12.6008 53 P<0.00001
Table 4: Baseline results.
Discussion
Antioxidant pathways in humans work synergistically to protect
body systems from free radical damage (Figure 5). Antioxidants
operate in biological systems in a lipophilic phase (example,
membranes or lipoproteins such as vitamin E and ubiquinols) or
aqueous phases such as ascorbate, glutathione, and thioredoxin [21].
e human body has several mechanisms to counteract oxidative
stress by producing antioxidants and recycling them. As part of an
antioxidant defense system. Vitamin E, vitamin C and glutathione play
a signicant role in antioxidant metabolism (Figure 5). Oxidized
glutathione and vitamin E and vitamin C have to be converted to their
antioxidant state, for the completion of the antioxidant cycle to prevent
the build of free radicals [22].
Vitamin C, for example, forms the transient ascorbyl radical which
is either quickly recycled to vitamin C, or when oxidative stress is high,
oxidized to form dehydroascorbic acid. Dehydroascorbic acid is
rapidly transported into cells (example: erythrocytes, leukocytes,
Dehydroascorbic acid) and is recycled by conversion back to vitamin C
by many enzyme systems. e recycling of Vitamin C includes
glutathione-dependent systems or reduced nicotinamide adenine
dinucleotide phosphate (NADPH)-dependent systems [23] (Figure 5).
Figure 5: Metadichol and Cellular Homeostasis.
Antioxidant regeneration pathway is limited by the availability of
glutathione, and vitamin C. We have previously shown that Metadichol
increases glutathione in Zucker diabetic rats [1]. Our explanation for
the observed increase in Vitamin C levels is that Metadichol by binding
with VDR increases glutathione levels and thus increases / maintains
required Vitamin C levels (Figure 5). is is not surprising given that
the natural ligand of VDR, 1,25(OH)2D is also known to participate in
the regulation of gamma-glutamyl transpeptidase, an enzyme which
up-regulates the glutathione (GSH) pool [24]. is eect was
associated with the activation of the redox-sensitive transcription
factor NRF2 and decreased activation of NF-kB [25,26]. Metadichol
inhibits NF-KB. e glucose-6-phosphate dehydrogenase (G6PD or
G6PDH) pathway supplies reducing energy to cells by maintaining
steady levels of NADPH, which maintains the level of glutathione to
protect cells against oxidative damage from compounds like hydrogen
peroxide [27].
Based on the results, we are now exploring the possibility that
Metadichol® perhaps may be activating the Gulo gene in the last step
for formation of Vitamin C (Figure 1). e implications of such a
development would lead that it could in principle to the eradication of
diabetes, blood vessel disease, cataracts, gallstones. e breakdown of
collagen with advancing age will be slowed. Ono can only imagine the
social, political and medical ramications if humans could extend their
lifespan by a decade or decades. We have shown that in this study,
Citation: Raghavan PR (2017) Metadichol® and Vitamin C Increase In Vivo, an Open-Label Study. Vitam Miner 6: 163. doi:
10.4172/2376-1318.1000163
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Vitam Miner, an open access journal
ISSN: 2376-1318
Volume 6 • Issue 2 • 1000163

Metadichol® is well tolerated and improves the quality of life of patients
with existing multiple medical conditions.
S.No Feedback and Observations
1 Weakness and tiredness disappeared, Patients felt physically active, and
this was expresses by all.
2 Mental Happiness; Interest in their work, concentration at work. Cooking
etc. Satisfaction was expressed by all people," I am happy".
Enthusiastic.
3 Acidity, Gastritis; Enhanced interest in food intake increased, and food
digestion was complete, and absorption, assimilation, and expulsion was
complete.
4 Arthritis; People could walk with ease and briskly with reduced pain.
5 Asthma; some patients cut completely or reduced to great extent their
inhaler use.
6 Back pain; some patients had much-reduced back pain.
7 Dry skin; Cleared in some patents.
8 Tan; Complexion enhancement has been seen in and reported by all
patients.
9 Dysuria; urination enhanced, frequent micturition stopped.
10 Headaches reduced.
11 Diabetes Millitus, Glucose and HbA1C levels reduced.
12 Hypertension; Reduction in blood pressure observed.
13 Sweating reduced.
14 Skin allergy; Good results were seen in Atopic Dermatitis, Skin rashes
subsided, Submucosal infection also subsided, Vaginal itching reduction
was also reported.
15 Voice clarity was observed and reported by one patient.
16 Loose motions; total relief reported by a few patients.
17 Constipation issues were resolved.
Table 5: Feedback and Observations.
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Citation: Raghavan PR (2017) Metadichol® and Vitamin C Increase In Vivo, an Open-Label Study. Vitam Miner 6: 163. doi:
10.4172/2376-1318.1000163
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Vitam Miner, an open access journal
ISSN: 2376-1318
Volume 6 • Issue 2 • 1000163