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original research
A Program Consisting of a Phytonutrient-rich
Medical Food and an Elimination Diet Ameliorated
Fibromyalgia Symptoms and Promoted Toxic-
element Detoxification in a Pilot Trial
Joseph J. Lamb, MD; Veera R. Konda, PhD; David W. Quig, PhD; Anuradha Desai, PhD; Deanna M. Minich, PhD; Lincoln Bouillon, MS, MBA;
Jyh-Lurn Chang, PhD; Alex Hsi, MPH; Robert H. Lerman, MD, PhD; Jacob Kornberg, MD; Jeffrey S. Bland, PhD; Matthew L. Tripp, PhD
Background • An effective treatment for fibromyalgia (FM) has
yet to become available.
Objective • To assess the efficacy of a lifestyle program consisting
of a modified elimination diet and a supplemental medical food
on clinical symptoms of FM assessed by the Fibromyalgia Impact
Questionnaire (FIQ ), FibroQuest Symptoms Survey (FibroQuest),
Medical Symptoms Questionnaire (MSQ ), metallothionein
mRNA expression, and urinary toxic element excretion.
Methods • Eight women (aged 48-74 years) were enrolled in an
8-week pilot trial employing a sequential design. During the
initial 4-week Program A (control), participants consumed a
modified US Department of Agriculture food pyramid diet and
a rice protein powder supplement that provided basic macro-
nutrient support. During the second 4-week Program B (inter-
vention), participants consumed a modified elimination diet
and a phytonutrient-rich medical food.
Joseph J. Lamb, MD, is director of Intramural Clinical
Research; Veera R. Konda, PhD, is director of the Department
of Molecular and Cellular Biology; Anuradha Desai, PhD, is
principal scientist of the Department of Molecular and
Cellular Biology; Deanna M. Minich, PhD, is vice president of
Research & Development Communications; Lincoln
Bouillon, MS, MBA, is senior manager of Clinical Research;
Jyh-Lurn Chang, PhD, is senior medical writer; Alex Hsi,
MPH, is a biostatistician; Robert H. Lerman, MD, PhD, is
director of Medicine and Extramural Clinical Research; Jacob
Kornberg, MD, is director of Professional & Clinical Services;
Jeffrey S. Bland, PhD, is chief science officer and president;
and Matthew L. Tripp, PhD, is vice president of Research &
Development, all at MetaProteomics LLC, Gig Harbor,
Washington. David W. Quig, PhD, is vice president of
Scientific Support of Doctor’s Data Inc, St Charles, Illinois.
Corresponding author: Joseph J. Lamb, MD
Email address: josephlamb@metagenics.com
36 ALTERNATIVE THERAPIES, mar/apr 2011, VOL. 17, NO. 2
Results • Compared to baseline, both programs showed trends
toward lower mean FIQ total score, MSQ total score, and
FibroQuest total score, FIQ stiffness score, and FibroQuest head-
aches score. Compared to Program A, Program B resulted in a sig-
nificant decrease (P < .05) in the FIQ pain score and stiffness score.
Participants also had better pain tolerance at five tender points
during Program B than during Program A. Higher metallothionein
mRNA expression was observed during Program B. An increase in
creatinine-adjusted mercury excretion and suggestive increase in
creatinine-adjusted arsenic excretion were noted when Program B
was compared to baseline. Urinary mercury/arsenic concentra-
tions were inversely associated with FIQ and FibroQuest scores.
Conclusions • Program B was shown to be a safe and effica-
cious botanically derived medical food treatment program for
the amelioration of FM symptoms. (Altern Ther Health Med.
2011;17(2):36-44.)
Disclosure
The study was conducted by MetaProteomics LLC and finan-
cially supported by MetaProteomics LLC and Doctor’s Data, Inc.
MetaProteomics is a subsidiary of Metagenics Inc that manufactur-
ers the study dietary supplement UltraClear MACRO and medical
food UltraClear RENEW for licensed health care professionals.
C
hronic conditions like fibromyalgia (FM), chronic
fatigue syndrome, and multiple chemical sensitivity
significantly affect the quality of life in a sizeable pro-
portion of the population. FM, characterized by
morning stiffness, fatigue, sleep disturbances, and
widespread pain, is estimated to affect 3.4% of women and 0.5% of
men in the United States.1 FM represents a significant financial
burden for our health care system. A recent epidemiologic survey
showed that the mean annual expenditures for FM patients,
approximately $11 000, are comparable to those for rheumatoid
arthritis patients.2 Twenty percent of these patients reported
Detoxification Program for Fibromyalgia Symptoms
short-term disability, and 65% had work absence days.2 Overall,
FM patients average 39.7 doctor visits per year.3
No clear-cut pathophysiological mechanism has been identi-
fied for FM. It has been suggested that FM is caused by central ner-
vous system malfunction leading to amplification of pain
transmission and interpretation,4 possibly related to neurotransmit-
ter imbalances.5 External stimuli, including infection, trauma, stress,
and toxicity, may contribute to the development of these imbalances.
Some have suggested that FM is a disorder of premature neurologic
aging.6 The lack of a clear etiology challenges the allopathic acute-
care model. All too often, acute-care medicine utilizes a reductionis-
tic “name it, and blame it” model. Diseases and particularly
syndromes, defined by signs and symptoms, are generally assumed
to have one cause and then treatments are selected. Hence, in the
absence of a unique etiology and defined biomarkers, FM is general-
ly diagnosed by exclusion. Indeed, in spite of the serious and perva-
sive disruption in a patient’s life, many practitioners and caregivers
continue to consider FM an entirely psychosomatic illness.
Using a different heuristic, the functional medicine model postu-
lates that complex diseases—FM, as a specific example—often can be
better addressed by restoring balance to basic dysfunctional physio-
logical processes. This approach provides valuable tools to the
researcher and clinician in the assessment of complex chronic diseas-
es such as FM. While it is generally assumed that FM has none of the
common inflammatory characteristics associated with other rheuma-
tologic conditions such as rheumatoid arthritis and systemic lupus
erythematosus, recent literature suggests that FM may be associated
with subtle signs of inflammation and immune dysregulation.7 Two
additional dysfunctions that contribute to an understanding of the
pathophysiology of FM are oxidoreductive imbalances resulting in
oxidative stress and the dysregulation of basic detoxification process-
es. The reduced ability to excrete toxins may play a role in the etiology
or exacerbation of a range of chronic diseases and conditions.8 Lyon et
al have suggested that hepatic detoxification and reduction of toxic
element burden may offer symptom relief.9
In addressing the imbalances that underlie FM, we chose to
focus on the homeodynamics of the body’s natural defenses against
toxic elements. A key component in toxic element excretion is metal-
lothionein, a protein rich in the constituent amino acid cysteine
(~30%), which has the ability to bind toxic elements including mercu-
ry, cadmium, lead, and arsenic.10,11 By binding and sequestering these
toxic elements, metallothionein prevents their biochemical interac-
tion with other biomolecules and reduces the production of reactive
oxygen species,10,12 thereby attenuating their toxicity,13 which may be
associated with FM symptoms.14 Promoter regions of the genes
encoding several Phase II biotransformation enzymes and metallothi-
onein contain several response elements including the xenobiotic
response element, the antioxidant response element, and the metal
response element.15 Signal transduction of external stimuli activates
the response elements and upregulates gene expression with resultant
induction of metallothionein and phase II biotransformation
enzymes. Preliminary work in our facility has demonstrated that cer-
tain phytonutrients—such as rho iso-alpha acids and spent hops
(Humulus lupulus), pomegranate rind extract (Punica granatum),
Detoxification Program for Fibromyalgia Symptoms ALTERNATIVE THERAPIES, mar/apr 2011, VOL. 17, NO. 2
prune skin extract (Prunus domestica), and watercress whole plant
extract (Nasturitum officinalis)—upregulate expression of mRNAs for
glutathione S-transferase, NADPH quinone reductase, and heme oxy-
genase-1, and spent hops upregulates expression of mRNA for metal-
lothionein in vitro (unpublished data).
Few therapies have resulted in demonstrable, predictable
improvement.16 Goldenberg et al have proposed that the approach
should be multimodal and include nonpharmacologic components,
including diet and lifestyle changes.17 Bland et al have previously
shown that a medical food-supplemented detoxification program
could improve chronic health problems.18 Here, we hypothesized that
a lifestyle program consisting of a modified elimination diet and a
novel phytonutrient-rich medical food may potentially be a safe and
efficient way to increase the excretion of toxic elements and to address
symptoms of FM. We conducted a pilot study to assess the efficacy of
this program on clinical symptoms and markers of biotransformation
and detoxification in subjects with FM. The primary endpoints were
the Fibromyalgia Impact Questionnaire (FIQ ),19 the Medical
Symptom Questionnaire (MSQ ), and the FibroQuest Symptoms
Survey (FibroQuest).20 These questionnaires have been used to track
subjective responses of patients to treatment in both clinical and
research settings. Secondary endpoints included the response of ten-
der points, whole blood metallothionein mRNA expression levels,
and urinary excretion of toxic elements.
MATERIALS AND METHODS
Participants
This was an 8-week pilot study that compared two novel lifestyle
programs for the management of FM and toxic element elimination
in eight adult women. Entrance criteria included the diagnosis of FM
based on American College of Rheumatology classification criteria21—
ie, 3 or more months of widespread pain, the presence of tenderness
in at least 11 of the 18 specified tender points, and the presence of four
or more current dental amalgams. Major exclusion criteria included
(1) history of significant liver, kidney or heart disease, uncontrolled
hypertension, HIV infection or AIDS, and serious mental illness; (2)
use of prescription and nonprescription medication and/or nutri-
tional supplements/medical foods for the support of detoxification in
the past 3 months; (3) changes in exercise routine in the past 2 weeks;
(4) pregnancy or lactation; and (5) allergy to one or more of the ingre-
dients in the investigational products. The study was conducted in
accordance with the Declaration of Helsinki and approved by the
Copernicus Institutional Review Board. Informed written consent
was obtained from each participant before enrollment in the study.
Trial Design
The study was conducted at the Functional Medicine
Research Center in Gig Harbor, Washington, from September to
November of 2008. The control arm (Program A) consisted of 4
weeks of a standard American diet (seafood excluded) with food
choices compliant with the US Department of Agriculture
(USDA) food pyramid guidelines plus twice daily supplementa-
tion with a rice protein powder supplement that provided basic
macronutrient support. The treatment arm (Program B) consisted
37
of 4 weeks of a hypoallergenic, modified elimination diet (seafood
excluded) plus twice daily supplementation with a phytonutrient-
rich medical food. Participants were asked to discontinue all sea-
food 1 week prior to the study and make no changes to any
current prescription or nonprescription medications or nutri-
tional supplements throughout the study (Figure 1). Each partici-
pant completed Program A before beginning Program B with no
washout period. In addition to the onsite screening visit, partici-
pants returned to the clinic seven times throughout the study,
during which fasting blood and 24-hour urine samples were col-
lected. At each visit, the study clinician assessed tender points
and grip strength; reviewed patient FIQ, MSQ, and FibroQuest
scores; assessed safety and tolerability; and reviewed compliance
to study product and dietary guidelines.
Measurement for Tender Points and Grip Strength
The same study clinician performed tender point measurement at
nine bilateral tender point sites. The clinician used a modified dolorim-
eter (Chatillon, Kew Gardens, New York) to apply pressure on each
location loading at approximately 1 kg per second and stopped when
the patient indicated pain or at 4 kg of force maximum. The numeric
value of each result was the amount of force tolerated by the participant.
The clinician also performed the grip strength test, an indicator
of overall strength. An adjustable dynamometer (Asimow
Engineering, Santa Monica, California) was used to measure the max-
imum force that a participant was able to exert with her hands. The
test was performed three times individually for each hand alternating
between dominant and nondominant hand in succession. The scale
for measurements ranged from 0 to 90 kg.

Exclude
seafood V1 V2 V3 V4 V5 V6 V7

W0 W1 W2 W3 W4 W5 W6 W7 W8
Program A Program B
Dietary guiedline USDA food pyramid FMRC dietary program
Seafood elimination Yes Yes
Elimination diet No Yes. Eliminate refined and added simple sugars,
artificial colorings, flavorings, and sweeteners;
caffeinated beverages; gluten-containing grains;
eggs and dairy products; and allergenic foods or
foods high in arachidonic acid

Supplementation Rice protein powder supplement Medical food (UltraClear RENEW)

(UltraClear MACRO)

Calories (per serving) 150 kcal 130 kcal

Macronutrients Total fat (4 g), saturated fat (medium chain; 2 g), total Total fat (3 g), saturated fat (medium chain; 1 g), total
carbohydrate (15 g), sugars (4 g), protein (15 g) carbohydrate (20 g), sugars (6 g), protein (12 g)

Fiber Mainly beet fiber and rice bran (3 g) Mainly cellulose gum, rice protein concentrate, and
spent hops (3 g)

Micronutrients Calcium (60 mg), iron (2 mg), phosphorus (350 mg), Beta-carotene (4000 IU), vitamin A (1000 IU), vitamin C
magnesium (200 mg), manganese (1 mg), sodium (300 mg), calcium (150 mg), vitamin D (35 IU), vitamin
(30 mg), potassium (730 mg) E (42 IU), thiamin (2 mg), riboflavin (2 mg), niacin (7
mg), vitamin B6 (3.4 mg), folate (80 μg), vitamin B 12
(3.6 μg), biotin (135 mg), pantothenic acid (36 mg),
sodium (220 mg), potassium (520 mg), iron (1 mg),
phosphorus (230 mg), iodine (53 μg), magnesium
(160 mg), zinc (10 mg), copper (1 mg), manganese
(1 mg), chromium (50 μg), sulfate (20 mg)

Botanical content No Yes. Spent hops (1 g), pomegranate rind extract (50
mg), prune skin extract (125 mg), watercress whole
plant extract (67 mg), and decaffeinated green tea
extract (15 mg)
Abbreviations: V, visit; W week; USDA, US Department of Agriculture; FMRC, Functional Medicine Research Center.

FIGURE 1 Study Design of the 8-week Study and the Description of Studied Lifestyle Programs

38 ALTERNATIVE THERAPIES, mar/apr 2011, VOL. 17, NO. 2 Detoxification Program for Fibromyalgia Symptoms
Laboratory Analysis
For metallothionein mRNA expression, RNA was first
extracted from whole blood using the RiboPure Blood RNA
Isolation Kit (Ambion, Austin, Texas) per manufacturer instruc-
tion. RNA was converted to first strand cDNA by use of the
RETROscript First Strand Synthesis Kit (Ambion) and primed
with oligo-dT according to the manufacturer’s specifications. A
Taqman gene expression assay to quantify GAPDH expression,
which was used as an endogenous control, was obtained from
Applied Biosystems (Foster City, California; assay ID
Hs99999905_m1). Forward and reverse primers and HPLC-
purified Taqman probes labeled with 5’-FAM and 3’-TAMRA were
obtained from Operon Biotechnologies, Inc (Huntsville,
Alabama). Primers and probes for Taqman-based assays targeting
human metallothioneins have been previously described.22 Two-
step Taqman-based RT-qPCR was performed. The cDNA equiva-
lent of 20 ng starting RNA was then included in qPCR reactions.
Reactions to detect metallothionein expression contained 1X
Taqman Master Mix (Applied Biosystems), forward and reverse
primers at 400 nM, and Taqman probe at 200 nM. Reactions to
detect GAPDH expression contained 1X Taqman Master Mix and
1X gene-specific assay reagents as recommended by the manufac-
turer. All reactions were run in triplicate. Reactions that did not
contain template cDNA were included as negative controls.
Reaction plates were processed on an Applied Biosystems 7900HT
Sequence Detection System. The AmpliTaq Gold polymerase was
activated at 95oC for 10 minutes, followed by 40 cycles consisting
of denaturation for 15 seconds at 95oC and annealing and exten-
sion for 60 seconds at 60°C. Amplification data was analyzed with
the ABI Prism SDS 2.1 software (Applied Biosystems). Relative
quantification of gene expression was performed by the ΔΔCt
method,23 with GAPDH expression serving as an endogenous con-
trol to normalize expression within each sample.
Urinary toxic element concentrations were measured using a
commercially available method, ICP-MS (Doctor’s Data, Inc, St
Charles, Illinois). Safety measures were also assessed by tracking
adverse events, vital signs, and performing safety blood tests.
Statistical Analysis
All eight women completed the study and were included in the
analyses. Each questionnaire was collected three times during each
treatment period, and the mean score at each period was calculated.
The mean scores were compared between the two treatment pro-
grams as well as between each individual program and the baseline
mean scores using two-sided paired t-tests. Tender points, grip
strength, and urinary toxic element excretion were analyzed with the
same methods. The metallothionein mRNA expression was present-
ed as fold induction over time relative to baseline expression. All data
are expressed as mean ± SEM.
RESULTS
Fibromyalgia Questionnaires
The eight enrolled participants were white females between
the ages of 48 and 74 years (55.6 ± 9.4) with BMI ranging from
Detoxification Program for Fibromyalgia Symptoms
20.4 to 44.8 (32.9 ± 9.5). Table 1 presents the scores of the subjec-
tive questionnaires from each participant at baseline and during
both treatment periods. Compared to baseline scores, both
Programs A and B showed trends toward lower mean FIQ total
score, MSQ total score, FibroQuest total score, FIQ stiffness
score, and FibroQuest headaches score, but only the MSQ total
score in Program A was statistically significantly lower than base-
line. Comparing the two programs, Program B resulted in lower
mean FIQ total score, MSQ total score, FibroQuest total score,
FIQ pain score, and FIQ stiffness score than Program A but only
reaching statistical significance (P < .05) in FIQ pain and stiffness
scores. There was a nonsignificant increase in FibroQuest head-
aches score in Program B compared to Program A.
Noting the review by Rooks24 and with the suggestion that a
treatment leading to a reduction in FIQ total score by 20% or
more to be clinically significant,25 we performed an analysis of
four “responders” who met the criterion (Figure 2). There were
suggestive trends that Program B resulted in stronger decrease in
all questionnaire scores than Program A.
Tender Points and Grip Strength
Compared to baseline, there was better pain tolerance at
four tender points (left occiput, left low cervical, right trapezius,
and right greater trochanter) during Program A and eight tender
points (left epicondyles, right knee, low cervical on both sides,
right trapezius, supraspinatus on both sides, and right greater
trochanter) during Program B (Table 2). Comparing both pro-
grams, participants during Program B had better pain tolerance
at five tender points (left epicondyles, both knees, left supraspi-
natus, and left gluteal) and worse pain tolerance at the second rib
on the right side. Grip strength on either side was not changed
throughout the study.
Urinary Excretion of Toxic Elements
Compared to baseline, the mean creatinine-adjusted uri-
nary mercury excretion was significantly increased during
Program A and Program B (Figure 3A). Our data suggested that
the mercury excretion was higher in Program B than in Program
A, although it did not reach statistical significance. There was a
trend toward increase (P = .056) in the mean creatinine-adjusted
urinary arsenic excretion during Program B but not Program A
in comparison to baseline; the difference between programs was
not significant (Figure 3B). Creatinine-adjusted cadmium levels
remained similar to baseline after either treatment program.
Compared to baseline, creatinine-adjusted lead levels decreased
significantly during Program B (P = .037) but not Program A; the
difference between programs was not significant. Using 24-hour
excretion data, similar findings were found for all four elements
(data not shown). Data from responders suggested that during
Program B their mean mercury excretion was higher than that
in all participants (1.83 µg/g creatinine and 1.73 µg/g creati-
nine, respectively; Figure 3A). Similar observation was found for
mean arsenic excretion (18.43 µg/g creatinine and 16.08 µg/g
creatinine, respectively; Figure 3B). Data of other toxic elements
ALTERNATIVE THERAPIES, mar/apr 2011, VOL. 17, NO. 2 39
 TABLE 1 Mean Scores of Multiple Fibromyalgia Questionnaires at Baseline and During Program A and Program B

Subject FIQ Total MSQ Total FibroQuest Total

Baseline A B Baseline A B Baseline A B

I (48) 53.9 70.4 71.9 160.0 165.0 200.7 65.0 75.7 92.3
II (52) 44.0 34.2 21.1 88.0 42.7 34.3 57.0 42.2 42.0
III (50) 43.0 42.8 31.4 64.0 54.3 45.3 52.0 46.0 37.3
VI (53) 57.9 49.8 48.6 109.0 113.7 114.3 82.0 63.7 62.3
V (50) 29.6 37.8 29.2 95.0 76.7 55.0 60.0 54.0 47.0
VI (68) 50.7 25.9 4.4 75.0 28.7 27.0 58.0 46.8 14.2
VII (57) 53.7 55.7 64.9 94.0 82.0 81.3 57.0 59.7 76.3
VIII (74) 37.8 31.9 21.5 70.0 42.7 40.3 53.0 42.2 34.0
Mean (SE) 46.3 (3.4) 43.6 (5.1) 36.6 (8.2) 94.4 (10.7) 75.7 (16.0)† 74.8 (20.6) 60.5 (3.4) 53.8 (4.2) 50.7 (8.9)

FIQ Pain FIQ Stiffness FibroQuest Headaches

Baseline A B Baseline A B Baseline A B

I (48) 6.00 9.00 7.67 7.00 8.00 8.00 4.00 3.33 7.67
II (52) 6.00 6.00 5.50 5.00 4.67 1.33 5.00 2.50 2.00
III (50) 7.00 6.00 4.67 5.00 3.67 1.67 5.00 6.00 5.33
VI (53) 7.00 6.33 6.67 7.00 5.33 4.33 9.00 7.00 8.00
V (50) 0.00 4.00 2.67 2.00 6.33 3.67 5.00 1.33 5.00
VI (68) 7.00 5.17 1.50 8.00 4.83 1.33 1.00 0.67 0.00
VII (57) 6.00 6.33 7.33 6.00 7.33 7.33 4.00 5.00 6.00
VIII (74) 5.00 4.67 3.33 7.00 6.00 4.00 10.00 1.00 1.00
Mean (SE) 5.5 (0.82) 5.94 (0.53) 4.92 (0.80)* 5.88 (0.67) 5.77 (0.51) 3.96 (0.92)* 5.38 (1.02) 3.25 (0.87) 4.38 (1.07)
Note: Fibromyalgia Impact Questionnaire (FIQ ) ranges from 0 to 80; Medical Symptoms Questionnaire (MSQ ) ranges from 0 to 284; FibroQuest Symptom Survey
(FibroQuest) total score ranges from 0 to 120; FIQ pain score ranges from 0 to 10; FIQ stiffness score ranges from 0 to 10; FibroQuest headaches score ranges from 0
to 10. Higher scores indicate more severe symptoms. A = Program A (wk 1-wk 4); B = Program B (wk 5-wk 8).
Each individual score under Program A and Program B represents the mean scores from 3 weekly measurements within the treatment period.
*Statistically significant (P < .05) comparing the average scores between the two treatment periods using 2-sided paired t-test.
†Statistically significant (P < .05) comparing the average scores of either program to baseline scores using 2-sided paired t-test.

50 FIQ total score 90 MSQ total score 60 FibroQuest total score

80 50
40 70
30 60 40
50 30
20 40
30 20
10 20 10
43.9 33.7 19.6 10 74.3 42.1 36.8 55 44.3 31.9
0 0 0
Baseline Program A Program B Baseline Program A Program B Baseline Program A Program B

8 FIQ pain score 8 FIQ stiffness score 8 FibroQuest headaches score

7 7 7
6 6 6
5 5 5
4 4 4
3 3 3
2 2 2
1 6.25 5.46 3.75 1 6.25 4.79 2.08 1 5.25 2.33 2.08
0 0 0
Baseline Program A Program B Baseline Program A Program B Baseline Program A Program B
FIGURE 2 Mean Scores of Multiple Fibromyalgia Questionnaires at Baseline and During Both Intervention Programs Among Responders (N=4)
Note: Scores for Program A and Program B represent the mean scores from 3 weekly measurements within the treatment period. Error bars represent SEM.
Abbreviations: FIQ, Fibromyaligia Impact Questionnaire; MSQ, Medical Symptoms Questionnaire.

40 ALTERNATIVE THERAPIES, mar/apr 2011, VOL. 17, NO. 2 Detoxification Program for Fibromyalgia Symptoms
 TABLE 2 Mean Tender Point and Grip Strength Measured at Baseline and During Program A and Program B
Baseline A B
Mean ± SE Mean ± SE Mean ± SE P value*
Tender Point
Second rib L 1.08 ± 0.30 0.92 ± 0.17 1.07 ± 0.21 .404
Second rib R 1.13 ± 0.23 1.14 ± 0.13 0.78 ± 0.14 .008
Epicondyles L 0.83 ± 0.21 1.06 ± 0.19 1.59 ± 0.19† .038
Epicondyles R 1.04 ± 0.14 1.19 ± 0.18 1.48 ± 0.26 .216
Knee L 1.58 ± 0.41 1.29 ± 0.29 1.93 ± 0.23 .002
Knee R 1.24 ± 0.21 1.28 ± 0.26 1.80 ± 0.27† .012
Occiput L 0.85 ± 0.17 1.40 ± 0.29† 1.56 ± 0.42 .521
Occiput R 0.93 ± 0.25 1.30 ± 0.27 1.39 ± 0.38 .625
Low cervical L 1.20 ± 0.34 1.68 ± 0.39† 2.08 ± 0.42† .184
Low cervical R 1.01 ± 0.23 1.60 ± 0.33 2.01 ± 0.38† .111
Trapezius L 1.60 ± 0.31 2.10 ± 0.35 2.30 ± 0.38 .309
Trapezius R 1.63 ± 0.29 2.11 ± 0.35† 2.35 ± 0.39† .237
Supraspinatus L 1.81 ± 0.50 2.18 ± 0.43 2.59 ± 0.47† .024
Supraspinatus R 1.90 ± 0.45 2.19 ± 0.45 2.41 ± 0.42† .139
Gluteal L 2.35 ± 0.40 2.70 ± 0.33 2.94 ± 0.31 .041
Gluteal R 2.40 ± 0.39 2.75 ± 0.32 2.68 ± 0.36 .613
Greater trochanter L 1.81 ± 0.39 2.16 ± 0.26 2.38 ± 0.31 .364
Greater trochanter R 1.75 ± 0.25 2.35 ± 0.32† 2.43 ± 0.29† .635
Grip Strength
First L 21.13 ± 1.81 21.00 ± 1.63 20.29 ± 1.50 .225
Second L 20.63 ± 1.71 20.08 ± 2.13 20.00 ± 1.78 .935
Third L 21.00 ± 2.03 20.17 ± 1.79 20.17 ± 2.03 .999
Derived average L 20.92 ± 1.71 20.47 ± 1.85 20.24 ± 1.77 .771
First R 24.13 ± 1.34 24.17 ± 2.10 23.04 ± 1.90 .073
Second R 23.00 ± 2.21 22.83 ± 2.01 23.13 ± 1.99 .613
Third R 23.25 ± 2.41 22.42 ± 2.14 22.96 ± 2.06 .527
Derived average R 23.46 ± 1.88 23.14 ± 2.06 23.04 ± 1.96 .866
Note: A = Program A (wk 1-wk 4); B = Program B (wk 5-wk 8). Each individual score under Program A and Program B represents the mean scores from 3 weekly
measurements within the treatment period.
*Statistically significant (P < .05) comparing the average scores between the two treatment periods using 2-sided paired t-test.
†Statistically significant (P < .05) comparing the average scores of either program to baseline scores using 2-sided paired t-test.

did not show changes over time or between two programs,
either in all participants or in responders only.
When evaluating the association between questionnaire
scores and the creatinine-adjusted urinary heavy metal excretion,
we found that the urinary mercury concentration was inversely
correlated with the FIQ pain score (R = -0.306; P = .02), and the
urinary arsenic concentration was inversely correlated with FIQ
total score (R = -0.360; P = .007), FibroQuest total score (R =
-0.312; P = .022), and FIQ pain score (R = -0.394; P = .003). Urinary
cadmium and lead concentrations were not associated with any
questionnaire score except that cadmium was positively associat-
ed with MSQ total score (R = 0.331; P = .014).
Metallothionein mRNA Expression
Compared to the baseline, the metallothionein mRNA
expression measured at the end of Program A (the end of week 4)
increased by 7%. The expression measured at the end of Program
B (the end of week 8) increased by 54% (Figure 4).

Detoxification Program for Fibromyalgia Symptoms ALTERNATIVE THERAPIES, mar/apr 2011, VOL. 17, NO. 2 41
 A. Urinary mercury
2.5 All participants 2.5 Responders
P=.020
2.0 2.0

μg/g creatinine
μg/g creatinine

P=.028
1.5 1.5

1.0 1.0

0.5 0.5
0.99 1.36 1.73 0.98 1.16 1.83
0.0 0.0
Baseline Program A Program B Baseline Program A Program B

B. Urinary arsenic

25 All participants 25 Responders

20 P=.056 20

μg/g creatinine
μg/g creatinine

15 15

10 10

05 05
11.24 13.23 16.08 12.63 13.60 18.43
0 0
Baseline Program A Program B Baseline Program A Program B
FIGURE 3 Creatinine-adjusted Urinary Mercury Excretion From (A) All Participants (N=8) and (B) Responders (N=4)
Note: Numbers for Program A and Program B represent the mean levels from 3 weekly measurements within the treatment period. Error bars represent SEM.
P values indicate significance compared to baseline.

rhea, gastrointestinal hypermotility, lethargy, hypersensitivity,

2
upper respiratory tract infection, urinary tract infection, muscle
1.8
spasms, myalgia, headache, nocturia, pruritis, and rash. One of
1.6
21 AEs was deemed to be possibly related to use of the rice pro-
(relative to baseline)

1.4
Fold Induction

tein powder supplement. No AEs were deemed to be related to

1.2 use of phytonutrient-rich medical food. No severe or serious AEs
1 occurred during the study.
0.8 End of
program B
0.6 DISCUSSION
End of
0.4 program A Simms et al compared a variety of parameters designed to
0.2 assess clinical outcome in FM patients, including sleep patterns, ten-
0 der points, and a global assessment of physical functioning.26 Their
Baseline W2 W4 W5 W6 W8
results suggest that, despite the clinical importance of pain as a car-
FIGURE 4 Average Metallothionein mRNA Expression Over Time dinal feature of FM, improvement in pain alone did not discriminate
Note: Data are fold induction compared to baseline. Baseline expression was as well as did a combination of outcome measures. Thus, question-
normalized to 1.0. The error bars represent SEM. naires evaluating different aspects of fatigue and functioning should
be included with tender point analysis when assessing response to
Safety therapy for FM. In this 8-week pilot trial in which eight FM patients
Both programs were well tolerated. During the 8 weeks, six underwent two lifestyle programs, we found that the 4-week regi-
of eight participants experienced a total of 20 mild adverse men of modified elimination diet supplemented with a phytonutri-
events (AEs) and one moderate AE (10 during Program A and 11 ent-rich medical food (Program B) reduced symptom scores on
during Program B), with symptomatology consistent with detoxi- multiple FM questionnaires, increased urinary mercury and arsenic
fication or deemed to be unlikely associated with consumption of excretion, increased pain tolerance at eight tender points, and
either product. Reported symptoms included constipation, diar- increased metallothionein mRNA expression. In comparison,

42 ALTERNATIVE THERAPIES, mar/apr 2011, VOL. 17, NO. 2 Detoxification Program for Fibromyalgia Symptoms
Program B was more effective than the standard American diet sup-
plemented with a rice protein powder supplement (Program A) in
reducing FIQ pain and stiffness scores, increasing urinary mercury
and arsenic excretion, increasing metallothionein mRNA expression,
and reducing tender point sensitivity.
FM is a complicated syndrome, and a reductionistic allopathic
medicine approach is unlikely to find a unifying etiology as caus-
ative in all patients who experience the illness. This has been
acknowledged in the direction that clinical research studies have
taken in their focus on the symptoms experienced by these partici-
pants. Marcus concludes in his recent review, “Fibromyalgia is a
common, disabling, chronic pain condition that predominately
affects women. Symptoms can be effectively treated using both
drug and nondrug therapies,” and further, “The strongest evidence
suggests effective treatment of fibromyalgia with duloxetine and
milnacipran. Studies also report efficacy with gabapentin,
pramipexole, pregabalin, tramadol, and IV tropisetron.”27 The
broad spectrum of pharmacological choices suggests that the focus
on symptom management rather than pathophysiologically cen-
tered therapy is the standard approach. Indeed, Lawson states that
“the primary focus of RCTs has often been toward pain manage-
ment; however, marked efficacy (a ≥50% decrease in pain) was lim-
ited to subgroups of patients, while the majority only gained
marginal benefits. These findings suggest that a single drug class
may not be sufficient to manage the condition.”28
Much attention has been given to the recent FDA approval of
pregabalin (Lyrica, Pfizer, New York, New York) for the treatment
of FM. One trial conducted to support this approval was the
Fibromyalgia Relapse Evaluation and Efficacy for Durability of
Meaningful Relief (FREEDOM) trial.29 In this trial, 1051 people
were enrolled in the initial 6-week open-label run-in treatment
with increasing doses of pregabalin; only 566 (53.8%) of partici-
pants responded (≥50% reduction in pain scored on a visual analog
scale) and were randomized to the second phase of a double-blind
withdrawal trial. During the open-label period, 178 participants
(17%) discontinued due to treatment-related adverse events. The
primary outcome was time to loss of therapeutic response postran-
domization. While a statistically greater number of pregabalin
patients did not lose therapeutic response, it is hard to imagine
that participants remained truly blinded with the difference in AEs
associated with the two treatments. As such, placebo patients were
likely to realize that they had been randomized to placebo instead
of the active substance with which they had been previously treat-
ed. Though it is inherently difficult to compare exploratory work
to large clinical trials with different designs, we did find that half of
the participants in our trial responded (ie, ≥20% reduction in total
FIQ score, a less rigid criterion) during the active treatment phase,
yet no differences in adverse event occurrence were noted between
Program A and Program B.
The functional medicine model, with its exploration of con-
tributing pathophysiological imbalances, provides an etiologic
understanding of FM. We focused on specific imbalances related
to hepatic biotransformation and detoxification in general and
specifically of toxic elements, which are the principles behind the
Detoxification Program for Fibromyalgia Symptoms
design of the Program B intervention in this trial. Our findings of
increased urinary mercury and arsenic excretion correlated with
reductions in FIQ pain and stiffness scores confirm Program B’s
ability to intervene in addressing pathophysiology and not simply
symptomatology.
Granted, nutraceuticals and pharmaceuticals may serve differ-
ent roles in the treatment of FM. Nonetheless, the modified elimi-
nation diet supplemented with a phytonutrient-rich medical food
offers multiple unique advantages for use in this population of
patients. The medical food used in Program B provides specific
nutrients that may be lacking in the diet of FM patients and those
patients who may benefit from additional support of hepatic detoxi-
fication and elimination of toxic elements. In addition to rho iso-
alpha acids and spent hops, pomegranate rind extract, prune skin
extract, and watercress whole plant extract, the medical food also
includes low allergy potential rice protein concentrate with added
limiting amino acids L-lysine and L-threonine to increase the bio-
logical value of the protein. Other ingredients include glycine, tau-
rine, sodium sulfate, and catechins from decaffeinated green tea to
support hepatic detoxification.
Even though our intervention led to favorable outcomes relat-
ed to FM symptom reduction and toxic element excretion, we rec-
ognize several limitations of this pilot study. With only eight
participants in this trial, small sample size and interindividual dif-
ferences are likely to limit the statistical power to detect treatment
effects. The generalization of the study finding to a large population
should be conducted with caution, as the selected sample may not
be representative. Each intervention lasted 4 weeks; future studies
are required to assess the intermediate- and long-term effects of
treatment. The study’s sequential treatment design did not ran-
domize individuals to either the treatment or the control arm.
In studies without a washout period between treatments, the
effect of the first treatment period may carry over to the second
treatment period. In our study, participants were not aware of
which treatment program represented the active phase; they were
only informed that the study was to compare two different pro-
grams. Clinically, it is often noted that there is a honeymoon or pla-
cebo effect with the introduction of new therapies. Wash-in periods
or control interventions allow for this effect, as these effects are gen-
erally transitory. No loss of benefit was noted during Program A,
and benefit was maintained and extended during Program B.
During the first diet period (Program A), participants were instruct-
ed to follow a standard American diet based upon the USDA food
pyramid recommendations. For many participants, this resulted in
the elimination of refined carbohydrates, saturated fats, and partial-
ly hydrogenated trans-fatty acids while a quality source of rice pro-
tein was added through the use of a nutritional supplement. These
changes represent a modification of the baseline diets with proin-
flammatory characteristics and may well have had therapeutic ben-
efit, thus masking a possible honeymoon effect. Regardless of the
explanation for benefit gained during Program A, Program B was
therapeutically stronger.
In conclusion, the 4-week modified elimination diet supplement-
ed with a phytonutrient-rich medical food has been demonstrated to
ALTERNATIVE THERAPIES, mar/apr 2011, VOL. 17, NO. 2 43
be an efficacious, whole food–based dietary program for the treat-
ment of fibromyalgia, with a uniquely benign side effect profile.
Further studies are planned in our research center to expand this work
to larger and more diverse populations.
Acknowledgments
We thank Cynthia Baxter, Meraf Eyassu, Kim Koch, and Leslie Pilkington for expert techni-
cal assistance.
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