ARTHRITIC EPISODES IN PATIENTS WITH VARIOUS AUTO-IMMUNE
DISEASES CHARACTERIZED BY THE COMMON TERMINOLOGY, ARTHRITIS AND PSORIASIS.
A Randomized Clinical
Published 1997, Second Quarter
H. Siemandi, M.D., et al
Objective. Recent published reports offer
anecdotal evidence that Cetyl Myristoleate may provide significant amelioration of various
arthritic conditions. We set out to perform controlled studies to determine if this
material was efficacious, either in the short term, or in some measurable manner, over a
much longer period.
Methods. A prospective, randomized study
design was used to allocate patients to receive Cetyl Myristoleate, Cetyl Myristoleate
plus Glucosamine hydrochloride (GH), sea cucumber (SC) and hydrolyzed cartilage (HC) and a
At the start of this study, the duration, severity, and pattern of arthritic episodes
were found to be similar in the 3 treatment groups. At the end of the study it was found
that the number of arthritic episodes was significantly reduced, and the duration of
episode-free time was significantly prolonged, in the two Cetyl Myristoleate groups
compared with the placebo group.
Conclusion. Cetyl Myristoleate treatment and Cetyl
Myristoleate plus GH, SC & HC were demonstrated to offer significant benefits over the
placebo in the prevention of arthritic episodes. It was further determined that these
results could not be obtained with other standard arthritic therapies based upon
exhaustive reviews of patient records prior to opening of the study. Cetyl Myristoleate
and Cetyl Myristoleate plus GH, SC & HC treatment also seems to permit some relief to
autoimmune inflammatory diseases, which may prove to be long-term. This finding could
provide additional evidence for the theory, reflected by the earlier anecdotal evidence as
well as some animal studies, that Cetyl Myristoleate and Cetyl Myristoleate plus GS, SC
& HC may prove to be of major benefit in the future treatment of autoimmune diseases.
The terms ARTHRITIS AND PSORIASIS have come to some
permanent and some transient. Each condition, however, is typified by certain common
elements such as some sort of inflammatory response with resulting pain, various forms of
cellular degeneration and frequently, permanent loss of mobility and quality of life.
With the exception of Osteoarthritis,
most researchers are beginning to believe all arthritic conditions may have a common,
albeit many-faceted, etiology - autoimmune dysfunction. Unfortunately the great number and
complexity of immune system components and their diverse interplay has made this theory
difficult to prove.
While it has not been proven, the original research done on Cetyl
Myristoleate at NIH indicates a direct connection between the observed effect of Cetyl
Myristoleate and some ability of Cetyl Myristoleate to correct certain immune dysfunction,
which may cause many arthritic conditions.
Patients and Methods
Study design. The study was a 32 week (8 week
cycle, 4 in-hospital & 4 in follow-up), multi-centric, double-blind, randomized,
placebo-controlled parallel trial that compared the efficacy of Cetyl Myristoleate alone,
and Cetyl Myristoleate plus GS, SC & HC, administered over a period of 30 days, with
placebo, for the treatment of various forms of autoimmune diseases commonly characterized
as arthritis and psoriasis. Out of a dose of 90 grams of total fatty acid esters, 18 grams
constituted Cetyl Myristoleate. Those study patients who received the support nutrients
GS, SC, & HC were given a total dosage of 18 grams each of these nutrients.
The study was conducted under the auspices of the Joint European Hospital Studies Program.
This study was designed by a committee, which consisted of rheumatologists and
biostatisticians experienced in the development and execution of clinical trials.
Oversight of the study was accomplished by an executive committee, composed of the primary
researcher and primary statistician, selected participating investigators, consultants;
and an independent sight committee consisting of two experienced federally controlled,
state health department rheumatologists and one state health department biostatistician.
Patients were required to have inflammatory arthritis of at least one year duration in at
least one peripheral joint, excluding the shoulders and hips. Included in this parameter,
affected joints must have had joint tenderness and joint swelling of 2 on a four point
scale and joint patient-physician overall assessment of involvement ranging from; none -
mild - moderate - severe - very severe. The patients inducted into this trial for the
purposes of psoriatic testing were chosen on generally the same criteria - involvement of
epidermal involvement from: none - mild - moderate - severe - very severe.
Criteria for exclusion included unwillingness
to stop the use of tobacco and caffeinated beverages, at least for the duration of the
trial. Tobacco and caffeine use has been reported to greatly hamper the positive (if
anecdotal) result of the use of Cetyl Myristoleate. It also should be noted here that the
use of any other medication in all forms of arthritis as well as psoriasis were not
excluded as it was determined this would limit participation. It was also deemed advisable
to approximate as much as possible, conditions that would be found in the average
arthritic. One exception to this condition was the exclusion of patients showing
sensitivity to salicylates or ibuprofen, which were used as excipients in the placebo.
Potential participants with other
severe chronic conditions were excluded, as it was the opinion of the primary investigator
that this type of participant would limit the potential successful completion of the study
period. All patients had failed to respond to therapy with therapeutic doses of one of the
NSAIDs. All patients who took NSAIDs during the trial were required to be on stable
dosages for one month prior to entry and throughout the trial. No systemic or
intrarticular steroids were used. All
patients were fully informed and voluntarily consented to participate in the research
program. The study protocol was reviewed and approved by the federally controlled state
oversight committee. Prior to entry into this trial, each potential study participant was
informed of the nature, duration, and purpose of the study to be administered, and all the
potential benefits, inconveniences, and hazards that could reasonably be expected.
Patients received either one-half liter of pleasantly flavored oral liquid containing 18
grams of Cetyl Myristoleate or one-half liter of the same liquid with Cetyl Myristoleate.
Both liquids were carefully compounded so as not to be able to be differentiated. Each
patient was also given 180 capsules of the adjunctive medication containing a total each
of 18 grams GL, SC and HC. Identical capsules containing the placebo compound were also
distributed. The Cetyl Myristoleate topical liquid was distributed as a 25% concentration
in 60-ccs. lightly scented lotion and an identical placebo lotion with Cetyl Myristoleate.
The oral liquid was used with meals in one-teaspoon quantities, three times daily. Two
capsules of GL, HC & SC were taken with each meal, three times daily. The topical
lotion was used as needed and determined by each patient according to his or her own
Outcome measures of disease activity and therapeutic efficacy were obtained at the time of
screening (not more than four weeks before study entry), randomization at week zero, and
thereafter at weeks; 1, 2, 3, and 4. Outcome measures included a variety of
patient-reported, clinical, laboratory and radiographic assessments. Patient
self-assessment measures included morning stiffness, night pain, patient overall
assessment and Mobility Functional Index as determined by this published procedure.
Clinical assessment measures included joint counts, dactylitis, Enthesopathy Index,
Spondylitis Articular Index, chest expansion, modified Schobers test, and
finger-to-floor test as detailed elsewhere in this paper. Additionally, the presence of
symptomatic keratoderma, phalangeal and digital deformation as measured from a normal
range of vertical protrusion at rest were measured. These tests, singularly and
collectively were then compiled into a patient-by-patient qualitative scale as; none = O,
mild = 1, moderate = 2, severe = 3 and very severe =4. Laboratory assessment. Laboratory
evaluation included a urinalysis and complete blood cell count, with leukocyte
differential and reticulocyte count. Chemical surveys and a Westergren erythrocyte
sedimentation rate (ESR) determination were done at every visit by secondary researchers
daily in the two hospital settings. The C-reactive protein (CRP) level was evaluated at
the first and last day of the hospital stay. At the screening times, blood was drawn for
HLA-B27 typing and RF and ANA determinations.
At the screening visit, all patients had the following radiographs performed:
anteroposterior views of the pelvis and oblique views of the sacroiliac joints. Adverse
drug reactions (ADRs). Patients were screened for ADRs at every secondary
researchers visit. Patients were withdrawn from the study medication if any of the
following were found; WBC less than 3000/mm3, absolute polymorphonuclear count less than
100000/mm3, acute or progressive decrease in hemoglobin or hematocrit, proteinuria less
than 500 mg. for 24 hours, drug fever or significant rash.
The patients were queried at each secondary researchers visit regarding the dietary
supplement or topical lotion they had used. A capsule count for the trial medication was
done at each consultation to monitor compliance.
Biostatistical considerations. Each
patient was classified as a treatment responder or nonresponder based on the following
definition. Assessment measures were selected a priori, and criteria for clinical
improvement and worsening were defined for each patient self-assessment and physician
assessment (improvement category); joint pain/tenderness score and joint swelling score
(improvement = decrease by 30%; worsening = increase by 30%). Treatment response was then
defined as improvement in at least 2 of these 4 measures, one of which must be joint
pain/tenderness or swelling, and ITO worsening any of the 4 measures. The study was
designated with a 90% power for detecting a placebo response rate of 30% compared with a
Cetyl Myristoleate and Cetyl Myristoleate plus GS, SC & HC response rate of 50%,
assuming a 10% withdrawal rate. This resulted in a target sample size of 431 patients with
an actual sample size of 382.
In short, the analytical method was the change in primary and secondary outcome measures
from baselines to the last available follow-ups analyzed using t-tests for continuous data
and chi-square tests for ordinal and categorical data. Mixed-model analyses were done to
characterize the response patterns over time using SAS PROC MIXED for continuous data and
a program named MIXOR for categorical and ordinal data. All other analyses were conducted
using SAS version 6.08. All statistical tests were two-sided and P0.05 was the criterion
for statistical significance.
population. Four hundred thirty-one patients entered the study. Of these, 106
were randomized to receive Cetyl Myristoleate, 84 were randomized to receive Cetyl
Myristoleate plus GS, SC & HC; 226 received a placebo. Fifteen psoriatics received
Cetyl Myristoleate plus GS, SC & HC, plus CM-25% concentration topical at a 3X
quantity ratio. Even though the study was sponsored by the owners of the respective
private hospitals, recruitment was not limited to the typical fee-paying patients.
Approximately 27% of the patients were actively recruited in the respective local area.
Despite a prolonged accrual period and careful screening, the loss of approximately 11% of
the starting participants occurred largely because of the inability to stop the use of
tobacco and/or caffeinated beverages.
Fulfillment of final parameter of
study size was accomplished by the substantial excess of volunteers wanting to enter the
study - this coupled with the relatively short testing period required to validate the
effects of Cetyl Myristoleate and Cetyl Myristoleate plus GS, SC & HC. Statistical
Chart 1 outlines the baseline demographic, clinical, and laboratory variables. The
duration of disease was 12 years. The Westergren ESR and CRP levels were mildly elevated.
There were no statistically significant differences in any of these baseline parameters
between the patients taking Cetyl Myristoleate and Cetyl Myristoleate plus GS, SC & HC
and those taking placebo.
Compliance. Compliance for
both the Cetyl Myristoleate and Cetyl Myristoleate plus GS, SC & HC and placebo groups
was quite high. There was a statistical trend toward those in the Cetyl Myristoleate and
Cetyl Myristoleate plus GS, SC & HC group taking more tablets per day (96% compliance)
than those in the placebo group (86% compliance) (P = 0.08). The probability of this
observation was due to the rapid response of pain relief in the Cetyl Myristoleate groups.
Primary outcome measures.
The Oversight Committee defined response based on a decision rule as outlined in Patients
and Methods. Statistical Chart 1 shows that based on that definition of treatment
response, using the last-visit analysis, response rates were 63.3% in the Cetyl
Myristoleate group and 87.3% in the Cetyl Myristoleate plus GS, SC & HC group and
14.5% in the placebo group. Trends favoring Cetyl Myristoleate and Cetyl Myristoleate plus
GS, SC & HC groups were noted in components of the response definition. Physician
overall assessment showed an improvement of 58.1% for the patients using Cetyl
Myristoleate alone and 84.2% for the patients using Cetyl Myristoleate plus GS, SC &
HC. Patients experiencing worsening or no reaction totaled 1.0% in all groups, compared
with improvement of 13.9% in placebo gradient overall assessment demonstrated 59.2%
improvement in the Cetyl Myristoleate alone group and 88.2% in the Cetyl Myristoleate plus
GS, SC & HC. Patients experiencing worsening or no reaction totaled 1.0% in all
groups, compared with improvement of 16.1% in placebo group. Joint swelling scores
improved in 47.2% in patients using Cetyl Myristoleate alone and 77.2% in patients using
Cetyl Myristoleate plus GS, SC & HC. Patients experiencing worsening or no reaction
totaled 1.0% in all groups, compared with improvement of 21.1% in placebo group.
Secondary and laboratory
outcome measures. Analysis of secondary outcome results (Statistical Chart 2)
demonstrated a significant reduction in the Spondylitis Articular Index in the Cetyl
Myristoleate group and in the Cetyl Myristoleate plus GS, SC & HC-treated patients.
Trends favoring the Cetyl Myristoleate group and in the Cetyl Myristoleate plus GS, SC
& HC group were also seen in a reduced duration of early stiffness and in an
improvement in the fingers-to-floor result. Laboratory outcome measures showed some
statistically significant changes. Total neutrophils decreased in the Cetyl Myristoleate
group and in the Cetyl Myristoleate plus GS, SC & HC group compared with the placebo
group. The Westergren ESR significantly decreased in the Cetyl Myristoleate group and in
the Cetyl Myristoleate plus GS, SC & HC groups compared with the placebo group. The
CRP values were not significantly different and the values in ESR for the responders was
not statistically significant from the nonresponders.
Withdrawals and adverse
drug reactions. Statistical Chart 3 summarizes the data of patient exits from
the study. Forty-nine patients withdrew from the study before completing the study, 16
from the Cetyl Myristoleate and 10 from Cetyl Myristoleate plus GS, SC & HC groups, 2
from the psoriatic group, and 21 from the placebo group. Follow-ups in all groups averaged
approximately these measurements were combined, combined average - (mean ± SD 6.97 ±
.2.64 months) (P=.06). Withdrawal of consent was the most common reason for discontinuing
the study. Seven patients withdrew because of no improvement or worsening disease. Two
patients had to be withdrawn from the study because of concurrent illnesses requiring
conflicting medication. The majority of withdrawals, however, was the result of patient
addictions to nicotine, caffeine and alcohol and the patient inability to cease these
activities during the study period.
Statistical chart 2 displays the
percentages of study patients showing improvement in the primary outcome variables
(columns 1-3). The numbers to the right display the significance levels for the
differences between treatment groups (columns 4-6). All of the significant levels are much
less than 0.05, which means the differences between groups are considered statistically
valid. For all four primary outcome variables (treatment response, physician assessment,
patient assessment and joint swelling score), Cetyl Myristoleate & GS, SC, and HC did
significantly better than the Cetyl Myristoleate group, and the Cetyl Myristoleate group
did significantly better than placebo. The chart also displays the results for the
secondary outcome variables. The averages (mean average as opposed to median or mode) are
presented in columns 1-3 along with their standard deviations (statistical measurement of
data variations). Again, the numbers to the right display the significance levels for the
difference between treatment groups (columns 4-6). NS, means that there was no
significant difference between any measured groups labeled as such. When the groups are
significantly different from each other, the significance is displayed. None of the
secondary outcome variables were significantly different between the Cetyl Myristoleate
group and placebo. The Cetyl Myristoleate & GS, SC, HC, group did significantly better
than the placebo for dwelling score, Enthesopathy index, spondylitis articular index and
the modified Schobers test. The Cetyl Myristoleate & GS, SC, HC, group did
better than Cetyl Myristoleate alone for the joint pain/tenderness score and the modified
The results of this trial suggest that Cetyl Myristoleate and Cetyl Myristoleate
supporting formulas may be beneficial in the treatment of many forms of arthritic based
diseases, including: psoriatic arthritis. The definition of response was determined a
priori and included assessment of joint pain/tenderness and swelling as well as patient
and physician overall assessments. Cetyl Myristoleate and supporting formulas produced the
best treatment response by a factor of 72.8% more patients than did placebo. Considering
the components of response individually Cetyl Myristoleate and supporting formulas
resulted in 70.3% more patients having improved as assessed by physician, and 56.1% more
having improved joint swelling. Therefore, while the amount of treatment response using
Cetyl Myristoleate and Cetyl Myristoleate and supporting formulas seems to be consistent
with the treatment affects on joint counts, it is obvious that there is a statistically
significant improvement in the use of the CM with supporting formulas. The time-line based
response rate of Cetyl Myristoleate and Cetyl Myristoleate supporting formulas, not
adequately reflected in data, by patient, showed the majority of patients responding to
Cetyl Myristoleate and Cetyl Myristoleate supporting formulas did so within the first
three weeks. Also, not reflected in the data, was the continued use of Cetyl Myristoleate
and Cetyl Myristoleate supporting formulas beyond the study time limits and dispensed on
request to 21 patients. These 21 patients were determined to have received only marginal
benefits from Cetyl Myristoleate and Cetyl Myristoleate supporting formulas but one more
course of treatment showed responses approximately equal to the first patient response
Cetyl Myristoleate and Cetyl Myristoleate supporting formulas were well tolerated in this
trial. This finding was not unexpected as Cetyl Myristoleate and the Cetyl Myristoleate
supporting formula components are naturally occurring and have been used as diet
supplementation for many years and are widely available singly and in various
combinations. In summary, Cetyl Myristoleate and Cetyl Myristoleate supporting formulas
appear to be beneficial in the treatment of a wide range of arthritic conditions including
long standing and refractive cases.
Statistical Chart #1
|Number of Patients
Statistical Chart #2
|Doctor Overall Assessment
|Patient Overall Assessment
|Joint Swelling Score
Statistical Chart #3
|Increased Liver enzymes
|Withdraw from Study
|Adverse Material Reaction
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