observational survey research - grey defence
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Observational Survey Research The Grey Defence User Experience
ABSTRACT
Purpose
Conduct an observational study of existing users of the dietary supplement Grey Defence® to determine its
effectiveness in reversing grey hair. The scope of this application is proposed to fall under a health claim based
on newly developed scientific evidence and include a request for the protection of enclose data as
confidential.
Results
In the study, 100 customers were contacted after using Grey Defence® for at least 5 months and asked to
participate in a product impact study. No compensation was promised or given to the participants. The survey
had a 20% response rate. Of the 20 respondents 13 (65%) indicated that they saw grey hair reversal. This
varied according to how long they had been on the product starting as low as 5% and going as high as 75%. A
T-Test was conducted to determine the statistical significance of the outcomes (percentage reversals). The
outcomes were deemed meaningful (statistically significant) at 99.99% level of confidence and Grey Defence®
was found to effectively reverse grey hair.
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INTRODUCTION
Grey Defence® was formulated to assist the body in reversing grey hair caused by the bleaching effects of
hydrogen peroxide (H2O2) and/or Vitamin B12 and Folic Acid deficiency. Grey Defence® contains essential
amino acids, vitamins and enzymes that form a catalytic force for the metabolic breakdown of H2O2 found in
hair bulb. Assuming normal melanogenesis, in the absence of H2O2 bleaching, the hair should return to its
natural pigmentation during the next anagen growth cycle.
Hydrogen peroxide is produced as a result of “respiratory burst” where the enzyme NADPH oxidase produces
large quantities of superoxides (free radicals) in the mitochondria of each cell as a by-product of the chemical
usage of oxygen (respiration). Superoxides are highly reactive oxygen species (ROS) and to protect the cells
they are quickly neutralized by the enzyme Superoxide dismutase to form hydrogen peroxide. Hydrogen
peroxide, itself also a highly reactive oxygen species, is quickly broken down by the enzymes Catalase and
Glutathione Peroxidase to form oxygen and water. The above three enzymes are produced throughout the
body and are collectively referred to as systemic enzymes.
As part of the aging process, overtime the body reduces the amount of systemic enzymes it produces. This
reduction in systemic enzymes allows minute quantities of H2O2 to escape neutralization. The escaped H2O2
stores itself at the base of the hair follicle (hair bulb) until it gets to a certain concentration that causes the
hair follicle to start greying. Grey Defence® contains Catalase and Selenium (which promotes the production of
Glutathione Peroxidase) to replicate the natural endogenous H2O2 neutralization process that the body does
efficient during youth.
It was shown that the hair bulb of greying hair contains a relatively large concentration of H2O2 as compared to
non-greying hair [1]. Additional studies looked at the role of reactive oxygen species (ROS) in melanocyte
apoptosis and found a causal relationship [8, 9, 10, 15]. This has led to theories on ROS (specifically H2O2)
greying.
In several studies greying was attributed to having occurred due to the creation of an intrinsic release from the melanogenesis pathway caused by H2O2, ultimately yielding apoptosis of hair follicle melanocytes (HFMs) and DNA damage, [10]. Additionally, others have posited or concluded that the decline of melanogenesis is associated with loss of tyrosinase activity, which in turn was due to high concentration of H2O2 irreversibly deactivating the enzyme, thereby introducing a rate-limiting step in melanogenesis [1, 2, 3]. Schallreuter and others have independently demonstrated that the protein repairing enzyme methionine sulfoxide reductases A and B (MSRA and MSRB), are structurally damaged and functionally altered by H2O2-mediated oxidation. This H2O2-mediated oxidation of MSRA and MSRB presents a rate limiting step in melanogenesis as well as prevents the hair follicles from being able to repair themselves [11, 12, 13, 14], however this was found to be reversible with the removal of H2O2 [1]. It has been shown in several human studies that the addition of Selenium to diets increase blood serum levels of Glutathione Peroxidase [4, 5, 3]. Additionally, Oien and Moskovitz [16] demonstrated that Selenium increased the expression of the MSRA and MSRB in mammals. This is because selenium and MSRA are positive expression-regulators of the selenoproteins. MSRB1 and Glutathione Peroxidase are examples of selenoproteins. This finding elucidates a potential pathway through which Grey Defence® may promote the production of both Glutathione Peroxidase and MSRB1, thereby accelerating the grey hair reversal process by (a) the breakdown of H2O2 while simultaneously (b) repairing the methionine sulfoxide reductase (MSR)
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system by promoting the increase production of MSRB1; allowing the hair to repair its melanogenesis pathway by removing the rate-limiting steps mentioned above.
Grey Defence® is also designed to address greying due to nutrient deficiency. Several studies looking at vitiligo
stressed the importance of the nutrients Vitamin B12 and Folic Acid in melanogenesis [6, 7]. Grey Defence®
provides very concentrated doses of these two B vitamins in addition to vitamin B6 which is used up in
melanogenesis in the production of melanin.
GREY DEFENCE® THEORETICAL MODES OF ACTION
Greying is not only a sign of wisdom and experience (results of chronological aging) – which is venerated – but
it is also the embodiment of the ravages of biological aging, where the buildup of metabolic junk causes the
atrophy of cellular vitality and the manifestation of morbidity. The process of reversing greying involves a re-
invigoration of our cells with the removal of accumulated metabolic junk. In short, reversing greying hair is not
just a superficial indulgence, it is a health and wellness endeavor that can improve one’s quality of life,
delaying the onset of the frailty of old-age even as chronological aging marches on.
The oxidative theory of greying, alluded to in the studies referenced above, provide a clear pathway that links
all non-disease and non-nutrient related greying causes. Essentially, for healthy individuals, greying is a result
of reactions caused by reactive oxygen species (ROS greying), primarily H2O2.
ROS greying proceeds in two distinct stages, Stage I and Stage II.
In Stage I, greying is largely due to the bleaching of the hair follicle as it grows by H2O2, as well as, the
reversible impairment of the sulfoxide reductase repair mechanism by H2O2. In Stage I greying, the hair follicle
still maintains the ability to produce color since the undifferentiated melanocyte stem cell is still viable.
Therefore Stage I greying may be reversible with the simple removal of H2O2 from the hair bulb.
In Stage II greying, H2O2 engages in chemical reactions that oxidizes key cellular components in
undifferentiated melanocyte stem cells and/or surrounding support cells. Such reactions include, but are not,
limited to Fenton type oxidative reactions in the presence of iron; an initial first order blow is dealt to cells
whose electrons are stolen for the Fenton reaction, followed on closely by a secondary reaction that steals
additional electrons involving the highly reactive hydroxyl radical (HO•) that was created in the first reaction.
Combined, these reactions deliver a one-two punch that may lead to permanent cell damage [26]. This kind of
cell damage may lead to senescence or apoptosis, preventing the undifferentiated melanocyte stem cell from
dividing and creating daughter cells that can then differentiate and create melanin going forward.
Since oxidative modifications and shortening by reactive oxygen species (ROS) leads to ageing of
the somatic cells, it is expected that antioxidants and reactive free radical scavengers may play a
preventive role and possess anti-ageing properties. … The end-replication problem of shortening
every time there is a cell division will lead eventually to the elimination of telomeres which in turn
will lead to apoptosis or an irreversible growth arrest of the cells [25].
Stage II greying is referred to as genetic greying; in genetic greying the hair follicle loses the ability to create
melanin. Individual hair follicles undergoing Stage II greying cannot regain color with the simple removal of
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H2O2. To reverse Stage II greying, undifferentiated hair follicle melanocyte stem cells needs to be rejuvenated
(or repopulated) so that they can start to divide once more, creating future differentiated melanocyte
daughter cells.
Theoretically speaking, if Stage I greying is eliminated and Stage II greying had not previously commenced,
then it may be possible to delay the onset of Stage II greying indefinitely.
Grey Defence® was designed to work cumulatively overtime. In short, the higher the dosage and the longer
the time period for which said dosage applies, the larger the amount of reversal of greying that occurs. So, all
things being equal, a hypothetical consumer successfully using Grey Defence® would have a 2-dimensional
time series plot of likely reversal outcomes curving upwards and looking somewhat like Graph A.
However, the hypothetical time series plot of an ineffective treatment would resemble Graph B. Interestingly
Graph B would be the same for both an individual, as well as, a group of such individuals (population sample)
whose treatment with Grey Defence® was ineffective.
An effective treatment is defined as a statistically significant positive, non-zero percentage reversal outcome
(in percentage of grey reversed) set against time at a confidence level of 95%. The Null Hypothesis (H0) and
Alternate Hypothesis (H1) are succinctly expressed below.
H0: µ 0 ≤ 0 (Null Hypothesis) H1: µ1 > 0 (Alternate Hypothesis)
µ=mean
Since Grey Defence® was not formulated to reverse Stage II greying; the time series plot of a successfully
treated individual’s outcomes would differ from that of a sample population of such individuals because of
heterogeneity in the stages of greying within any random population. This is because in any random
population sample of such individuals (those successfully treated), greying would lay on a continuum starting
at Stage I greying and terminating just before those exhibiting only Stage II (yellow and pink area in Venn
diagram below). The hypothetical 2-dimensional time series plot of such a successful random population
would resemble Graph C.
Diagram A
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Graph A
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METHODS
Study Design This observational study was conducted on COORGA Nutraceuticals Corporation’s (COORGA) database of existing Grey Defence® users. Users purchased and used the product for a period of at least 5 months. The survey was conducted between February and March 2013. No compensation was promised or given to the participations. The study was conducted by investigators working for COORGA. Objectives:
Determine the safety and efficacy of Grey Defence® by way of an observational study of existing users who
have used Grey Defence® for a minimum of 5 months. An effective treatment is defined as a statistically
significant non-zero percentage reversal outcome over time set at a confidence level of 95%. The Null
Hypothesis then would be that reversal outcomes should be zero at all time periods and any changes observed
are due to random chance (noise in the data). Essentially a time series plot of the null hypothesis look like
Graph B.
Study Questions 1. Have you had any adverse reaction from using Grey Defence®? 2. What percentage, if possible to estimate, of your grey hair do you estimate has reverted to normal
coloring (e.g. 1%, 5%, 20%, etc.)? 3. What is your age? 4. What is your sex (male, female)? 5. At what age did you start greying? 6. Is there a history of premature greying in your family (greying before 28th birthday)? 7. Do you have a history of thyroid illness? 8. Have you ever been diagnosed as Vitamin B12 deficient? 9. Would you recommend Grey Defence® to a friend or family member? 10. Would you be willing to share your responses, with attribution, publicly on our website (i.e., first initial
and last name)? Dosage Characterization
The assumption is made that each participant uses Grey Defence® as directed on the label. The label instructed that two Grey Defence® capsules, representing a single serving, be taken once daily on an empty stomach. The Grey Defence® ingredients were liquefied in a glycerin base and encapsulated in a vegetarian enteric coated capsule. Each serving (2 capsules) contains the following ingredients: Vitamin B6 Folic Acid Vitamin B12 Selenium Astragalus membranaceous root extract Panax Notoginseng leaf extract Pterostilbene L-Methionine Catalase
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Time in Months
Equipment & Method: 100 healthy participants with greying hair ranging in age from 35 years to 71 years were selected for the
study. Each individual selected was required to have used Grey Defence® for a minimum of 5 months. At the
time of the study, 127 individuals satisfied this requirement, the first 100 (based on alphabetical listing) were
selected as candidates in the study.
Emails containing 10 questions were sent out to all participants with a valid email address. Of the emails sent
out 4 responses were received. All the remaining candidates not responding or having no email address were
contacted by telephone; this resulted in an additional 16 responses (see appendix interview recordings).
OUTCOME MEASURES
Participant Self-Reported Outcomes:
A final response rate of 20% was received with the combined email and telephone contact methods. Of the
respondents 65% indicated that they observed some level of color returning to their hair (please see Table 1 &
Graph 1).
Graph 1: Customer Response to ‘Question 2’ of Self Response Survey
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Table 1: Customer Response to ‘Question 2’ of Self Response Survey
Participant Time On Grey Defence® (Months) Percentage Grey Hair Reversed
L. Lund 5.1 30% - 40%
J. R. (withheld by request) 18.6 25%
E. Thayer 18.6 30%
R. M. (withheld by request) 9.7 0%
D. D. (withheld by request) 13.7 0%
M. R. (withheld by request) 12.9 5%
R. Brown 8.7 0%
N. N. (withheld by request) 10.2 40%
M. D. (withheld by request) 16.9 Not Sure
K. Maragni 13.3 60%
C. H. (withheld by request) 7.4 0%
D. S. (withheld by request) 16.9 40%
L. J. (withheld by request) 13.8 0%
R. L. (withheld by request) 17.1 Not Sure
V. K. (withheld by request) 13.4 25%
Roscoe 13.2 > 10% M. Wells 10.1 10%
R. Raman 12.9 75%
R. K. (withheld by request) 8.1 10%
K. Littsey 7.4 55%
Null Hypothesis: Reversal outcomes will be zero or negative at all time periods, any positive changes are random events. P Value = 0.000085919 | Null Hypothesis is false, outcomes are significant | 99.99% confidence level
DISCUSSION
Overall, Customers reported reversal levels as low as zero (no results) to as high as 75%. In total, 65% of
respondents saw some reversal (from 5% to 75%). Reversal was dose dependent – the longer one uses Grey
Defence® the higher the reported reversal amount.
While it would have been nice to have a larger data set thereby reducing the risk of a Type II error (failure to
reject the Null when it is in fact false), the results demonstrated a very high level of significance, allowing
strong conclusions to be drawn and Type II error was not a factor. Essentially, with 99.99% confidence level,
the data shows conclusively that Grey Defence® reverses grey hair. This is especially impressive for such a
small sample size where the results could have been biases towards the Null Hypothesis (no grey reversals);
instead 65% reported some positive reversal outcomes.
The resulting plot of customer responses (Graph 1) appears to be a combination of both Graph B and Graph C.
This makes sense especially given that Grey Defence® was design for Stage I ROS greying only and any random
population will resemble the Venn Diagram above - with Stage I (large reversal evidenced), Stage II (no
reversal evidenced) and individuals in both Stage I and Stage II to varying degree simultaneously (medium to
modest reversal).
To evaluate how well Grey Defence® reverses Stage I greying, it is necessary to remove the noise caused by
those individuals primarily in Stage II greying. Accordingly, the data needs to be scrubbed of such individuals,
which is accomplished by removing anyone who has not crossed the 40% reversal mark by their twelfth month
of usage. This demarcation was chosen to isolate the hypothetically ideal Stage I individual (yellow area of
Venn diagram). Such an individual should have at least 60% reversal by the end of their 16th month of
treatment and the 40/12 benchmark is in line with that. Table 2 and Graph 2 represent such a data scrub.
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Table 2: STAGE 1 Greying Customers
Participant Time On Grey Defence® (Months) Percentage Grey Hair Reversed
L. Lund 5.1 30% - 40%
N. N. (withheld by request) 10.2 40%
K. Maragni 13.3 60%
R. Raman 12.9 75%
K. Littsey 7.4 55%
Graph 2: STAGE 1 Greying Customers
SUMMARY
EFFICACY ASSESSMENT
None of the participants indicated that they had any health issues known to contribute to greying (thyroid
illness) and also none reported any known B12 or folic acid nutrient deficiency issues - it is then reasonable to
conclude that any greying experienced by this sample population is a result of ROS greying.
From the survey responses it is clear that Grey Defence® works to reverse ROS greying with a 99.99%
confidence level; 65% of respondent saw positive results.
Further, because ROS greying can be separated in an early and late stage, the employment of statistical
modelling techniques was used to determine how effectively Grey Defence® addressed Stage I ROS greying.
The results of these techniques were presented in Table 2 and Graph 2, and both clearly show that Grey
Defence® is very effective in reversing Stage I ROS greying. In fact, the sample population regression graph for
Stage I greying sample population shown in Graph 2, very closely approaches Graph A - the hypothetical ideal
successfully treated individual.
This observational study proves conclusively that Grey Defence® reverses grey hair.
SAFETY ASSESSMENT
There has been no reported adverse effects from using Grey Defence® (please see Table A in Appendix) and
therefore Grey Defence® may be deem safe or at a minimum to be a low risk for any serious adverse effects.
y = -0.0022x2 + 0.078x R² = 0.8489
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APPENDIX
Raw Data and References
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Reference
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