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Efficacy of the Autoimmune Protocol Diet as Part of a Multi-disciplinary, Supported Lifestyle Intervention for Hashimoto’s Thyroiditis

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  • Resilient Roots: Functional and Evolutionary Medicine

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Background Hashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is an autoimmune disorder affecting the thyroid gland and is the most common cause of hypothyroidism in the US. Despite medical management with thyroid hormone replacement, many individuals with HT continue to experience symptoms and impaired quality of life. Given the limited number of efficacious treatments outside of hormone replacement and the overall burden of continued symptomatic disease, this pilot study was designed to determine the efficacy of a multi-disciplinary diet and lifestyle intervention for improving the quality of life, clinical symptom burden, and thyroid function in a population of middle-aged women with HT. Materials and methods The study recruited 17 normal or overweight (body mass index (BMI) <29.9) female subjects between the ages of 20 and 45 with a prior diagnosis of HT. The 17 women participated in a 10-week online health coaching program focused on the implementation of a phased elimination diet known as the Autoimmune Protocol (AIP). The 36-Item Short Form Health Survey (SF-36) and Cleveland Clinic Center for Functional Medicine's Medical Symptoms Questionnaire (MSQ) were used to measure the participant's health-related quality of life (HRQL) and clinical symptom burden, respectively, before and after the 10-week program. The participants completed serologic testing that included a complete blood cell count (CBC) with differential, complete metabolic profile (CMP), thyroid function tests, including thyroid stimulating hormone (TSH), total and free T4, and total and free T3, thyroid antibodies, including thyroid peroxidase antibodies (TPO) and anti-thyroglobulin antibodies (TGA), and high-sensitivity C-reactive protein (hs-CRP). Results Sixteen women (n = 16) completed the SF-36 and MSQ before and after the 10-week program. There was a statistically significant improvement in HRQL as measured by all eight subscales of the SF-36 with the most marked improvements noted in the physical role functioning, emotional role functioning, vitality, and general health subscales. The clinical symptom burden, as measured by the MSQ, decreased significantly from an average of 92 (SD 25) prior to the program to 29 (SD 20) after the program. There were no statistically significant changes noted in any measure of thyroid function, including TSH, free and total T4, free and total T3 (n = 12), as well as thyroid antibodies (n = 14). Inflammation, as measured by hs-CRP (n = 14), was noted to significantly decrease by 29% (p = 0.0219) from an average of 1.63 mg/L (SD 1.72) pre-intervention to 1.15 mg/L (SD 1.31) post-intervention. Conclusions Our study suggests that an online diet and lifestyle program facilitated by a multi-disciplinary team can significantly improve HRQL and symptom burden in middle-aged female subjects with HT. While there were no statistically significant changes noted in thyroid function or thyroid antibodies, the study's findings suggest that AIP may decrease systemic inflammation and modulate the immune system as evidenced by a decrease in mean hs-CRP and changes in white blood cell (WBC) counts. Given the improvements seen in the HRQL and participants' symptom burden as well as markers of immune activity and inflammation, further studies in larger populations implementing AIP as part of a multi-disciplinary diet and lifestyle program are warranted.
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Received 03/05/2019
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Review ended 04/24/2019
Published 04/27/2019
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Efficacy of the Autoimmune Protocol Diet as Part
of a Multi-disciplinary, Supported Lifestyle
Intervention for Hashimoto’s Thyroiditis
Robert D. Abbott , Adam Sadowski , Angela G. Alt
1. Independent Researcher, Resilient Roots Functional and Evolutionary Medicine, Charlottesville, USA 2. Helfgott
Research Institute, National University o f Natural Medicine, Portland, USA 3. Independent Researcher, Co lumbia, USA
Corresponding author: Robert D. Abbott, rda4zf@virginia.edu
Disclosures can be found in Additional In formation at the end of the article
Abstract
Background
Hashimoto’s thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is an autoimmune disorder
affecting the thyroid gland and is the most common cause of hypothyroidism in the US. Despite medical
management with thyroid hormone replacement, many individuals with HT continue to experience
symptoms and impaired quality of life. Given the limited number of efficacious treatments outside of
hormone replacement and the overall burden of continued symptomatic disease, this pilot study was
designed to determine the efficacy of a multi-disciplinary diet and lifestyle intervention for improving the
quality of life,clinical symptom burden, and thyroid function in a population of middle-aged women with
HT.
Materials and methods
The study recruited 17 normal or overweight (body mass index (BMI) <29.9) female subjects between the
ages of 20 and 45 with a prior diagnosis of HT. The 17 women participated in a 10-week online health
coaching program focused on the implementation of a phased elimination diet known as the Autoimmune
Protocol (AIP). The 36-Item Short Form Health Survey (SF-36) and Cleveland Clinic Center for Functional
Medicine’s Medical Symptoms Questionnaire (MSQ) were used to measure the participant’s health-related
quality of life (HRQL) and clinical symptom burden, respectively, before and after the 10-week program. The
participants completed serologic testing that included a complete blood cell count (CBC) with differential,
complete metabolic profile (CMP), thyroid function tests, including thyroid stimulating hormone (TSH),
total and free T4, and total and free T3, thyroid antibodies, including thyroid peroxidase antibodies (TPO)
and anti-thyroglobulin antibodies (TGA), and high-sensitivity C-reactive protein (hs-CRP).
Results
Sixteen women (n = 16) completed the SF-36 and MSQ before and after the 10-week program. There
wasastatistically significant improvement in HRQL as measured by all eight subscales of the SF-36 with the
most marked improvements noted in the physical role functioning, emotional role functioning, vitality, and
general health subscales. The clinical symptom burden, as measured by the MSQ, decreased significantly
from an average of 92 (SD 25) prior to the program to 29 (SD 20) after the program. There were no
statistically significant changes noted in any measure of thyroid function, including TSH, free and total T4,
free and total T3 (n = 12), as well as thyroid antibodies (n = 14). Inflammation, as measured byhs-CRP (n =
14), was noted to significantly decrease by 29% (p = 0.0219) from an average of 1.63 mg/L (SD 1.72) pre-
intervention to 1.15 mg/L (SD 1.31) post-intervention.
Conclusions
Our study suggests that an online diet and lifestyle program facilitated by a multi-disciplinary team can
significantly improve HRQLand symptom burden in middle-aged female subjects with HT. While there were
no statistically significant changes noted in thyroid function or thyroid antibodies, the study’s findings
suggest that AIP may decrease systemic inflammation and modulate the immune system as evidenced bya
decrease in meanhs-CRP and changes in white blood cell (WBC) counts. Given the improvements seen in the
HRQL and participants’ symptom burden as well as markers of immune activity and inflammation, further
studies in larger populations implementing AIP as part of a multi-disciplinary diet and lifestyle program are
warranted.
Categories: Endocrinology/Diabetes/Metabolism, Family/General Practice, Internal Medicine
Keywords: autoimmune thyro id disease, hashimoto's thyroiditis, paleo diet, quality of life, lifestyle, health coach ing,
nutrition
Introduction
Hashimoto’s thyroiditis (HT) is the most common autoimmune thyroid condition and the overall cause of
hypothyroidism in the Western world, disproportionately affecting Caucasian females over men and other
ethnic groups [1]. HT is a complex disease with multiple etiologic factors, including environmental
1 2 3
Open Access Original
Article DOI: 10.7759/cureus.4556
How to cite this article
Abbott R D, Sadowski A, Alt A G (April 27, 2019) Efficacy of the Autoimmune Protocol Diet as Part of a
Multi-disciplinary, Supported Lifestyle Intervention for Hashimoto’s Thyroiditis. Cureus 11(4): e4556. DOI
10.7759/cureus.4556
exposures, drug use, pregnancy, nutritional intake, and infectious diseases [2]. Family and twin-based
studies have revealed various genetic susceptibilities primarily related to variations in an individual’s human
leukocyte antigen (HLA) genotype as well as variations in numerous cytokines and the vitamin D receptor
[2]. Given the complexity of HT, with numerous genetic contributors and our emerging understanding of
additional environmental mediators, further research in therapies that can positively modify known
environmental factors and mitigate risk for genetically susceptible individuals is warranted.
Currently, for individuals diagnosed with HT, there are few, if any, efficacious treatments outside of thyroid
hormone replacement. Winther et al. showed that, in a cohort of 78 consecutive individuals newly diagnosed
with HT, baseline markers of quality of life, as measured by the 36-Item Short Form Health Survey (SF-36),
were significantly lower than normative healthy controls [3]. Despite slight improvements in thyroid-specific
and mental-health-specific quality of life, individuals with HT persisted with overall lower quality of life as
compared to healthy controls even after six months of treatment with levothyroxine therapy [3].
Additionally, even after normalizing thyroid function via hormonal replacement, many individuals with HT
persist with numerous symptoms, such as chronic fatigue, dry skin, hair loss, chronic irritability, and
nervousness, impairing quality of life [4].
To address the need for additional therapeutic options targeted at improving quality of life and symptom
burden in individuals with HT, the objective of this study was to determine the efficacy of a multi-week diet
and lifestyle intervention implemented by a physician, a team of nutritional therapy practitioners (NTPs),
and health coaches. The study authors hypothesized that the multi-dimensional intervention would improve
the participant's HRQL as well as decrease the participant's clinical symptom burden. The study authors
additionally hypothesized that the intervention would improve thyroid function as measured by a decrease
in TSH and increases in free and total T3 and T4. It was speculated that some individuals would require less
thyroid replacement medication after the 10-week intervention. Finally, the study authors sought to explore
the effect of the 10-week intervention on inflammation and immune activity as measured by high-
sensitivity C-reactive protein (hs-CRP), white blood cell (WBC) count, differential cell counts, and thyroid
antibodies, including thyroid peroxidase (TPO) antibodies and anti-thyroglobulin antibodies (TGA).
There have beennumerousclinicaltrials evaluating the use of dietary interventions for a variety of
autoimmune diseases, including inflammatory bowel disease (IBD), multiple sclerosis, psoriasis, celiac
disease, autoimmune thyroiditis,and rheumatoid arthritis[5-11].A recent 2017 review assessed the role of
iodine, selenium, vitamin D, and gluten on the management of patients with HT [10]. The authors concluded
that the role of agluten-freediet may be of benefit for patients with HT independent of a comorbid diagnosis
ofceliac disease. Despite the potential benefit from this dietary elimination,they speculated, however, that
quality of lifecould be negatively impacted given therestrictive nature of the gluten-free diet.
Outside of our current understanding regarding the importance of certain key nutrients for the optimal
functioning of the thyroid gland, namely iodine, selenium, zinc, iron, B12, and lipid soluble vitamins,
includingA, E, D, and K, there are no specific dietary guidelines or recommendations for individuals with
autoimmune thyroid disease. While some have speculatedthat over-consumption of dietary goitrogens could
negatively impactthyroid functioning, there is an absence of rigorous trials suggesting the negative effects of
such foods when consumed in normal proportions.
In seeking to identify a dietary template and feasible lifestyle intervention that could positively improve
HRQL and symptom burden in individuals with HT, five criteria were outlined: (1) Consumption of foods
high in micronutrients containing, but not limited to, the aforementioned nutrients essential for thyroid
functioning; (2) Elimination of foods with low nutritional value (sugar-sweetened beverages, ultra-
processed foods, etc.) and foods that could result in an aberrant immune response via dysregulated antigen
presentation or detrimentally affect both the gut microbiome and the integrity of the gastrointestinal
barrier; (3) Implementation of dietary changes in phases, utilizing education and support from health
coaches, NTPs, and a physician to improve dietary adherence; (4) Facilitation of the dietary and lifestyle
intervention as part of an online community allowing participants to engage with other study members;
(5) Prior clinical evidence for the efficacy of the intervention for a specific autoimmune disease.
In light of these five criteria, the Autoimmune Protocol (AIP), as implemented within the “SAD (Standard
American Diet) to AIP in SIX” online, community-basedhealth coaching program was the dietary and
lifestyle program identified as most likely to result in participant adherence and symptom improvement.
AIP, as implemented by the “SAD to AIP in SIX” program, was previously studied in individuals with
inflammatory bowel disease (IBD) and was shown to be able to induce remission and improve symptoms in
over 70% of participants [5].
In terms of its dietary composition, AIP is a modification of the Paleolithic diet that begins with an
elimination of specific foods, dietary additives, emulsifiers, and western dietary patterns that have been
implicated in disrupting the flora of the gastrointestinal microbiome as well as the intestinal barrier, leading
to dysregulated antigen presentation and the development of autoimmunity [12-17].In addition to the
eliminated foods, AIP additionally promotes the consumption of nutrient-dense whole foods such as
vegetables, fruits, mono and polyunsaturated fatty acids, tubers, wild game, poultry, organ meats, and non-
processed meats.
Materials And Methods
Study design and measures
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 2 of 33
Prior to enrolling in the trial, advertising for the study was completed across various social media outlets and
local practitioners treating patients with HT. Upon receiving correspondence from interested participants,
communication was initiated by study investigators to assess the participants’ ability to enroll in the
intervention. A total of 456 subjects were screenedwith inclusion and exclusion criteria, resulting in 17
subjects eligible for inclusion in the trial. Inclusion criteria consisted ofEnglish-speakingmale or females,
20-45 years of age, with a diagnosis of HT and a body mass index (BMI) between 18.4 and 29.9. Exclusion
criteria consisted of individuals outside the listed age or BMI criteria, no definitive diagnosis of HT, prior
experience with AIP for >30 days, pregnant, breastfeeding, six months postpartum, presence of other
comorbidities, including hypertension, diabetes, heart disease, heart failure, liver failure, chronic or end-
stage kidney disease, use of medications outside of Food and Drug Administration (FDA)-approved thyroid
replacement medications, or an individual being unable to complete a two-week washout period before the
start of the trial. In selecting the inclusion and exclusion criteria, the study authors sought to identify
normal or overweight (non-obese) premenopausal women to minimize the influence of hormonal variations
between pre and post-menopausal women as well as to minimize the likelihood for rapid weight loss in
obese individuals. The study authors sought to minimize the risk of adverse effects, complications, and
variations in thyroid function secondary to other disease processes by excluding individuals with chronic
organ disease/organ failure as well as pregnant or breastfeeding women and women in the early post-partum
period.
The two-week washout period consisted of a screening visit prior to the initiation of the formal dietary
intervention wheresubjects signed informed consent, provided demographic information, completed study
questionnaires, including a validated quality of life survey, the 36-Item Short Form Health Survey (SF-36),
the Cleveland Clinic Center for Functional Medicine’s Medical Symptom Questionnaire (MSQ), and the
National Institutes of Health’s (NIH's) food frequency questionnaire (FFQ) [18-19]. Participants provided
fasting blood samples, including complete blood cell count with differential (CBC), complete metabolic
profile (CMP), thyroid stimulating hormone (TSH), free T4, free T3, total T4, total T3, reverse T3, thyroid
peroxidase (TPO) antibodies, anti-thyroglobulin antibodies (TGA), 25-hydroxycholecalciferol, and high
sensitivity C-reactive protein (hs-CRP).In addition,Genova Diagnostics Laboratory supplied organic acid
tests (NutrEvalFMV™, Genova Diagnostics Laboratory, NC, USA) as well as comprehensive stool analysis(GI
Effects™, Genova Diagnostics Laboratory, NC, USA)for participants to complete during the washout period.
After completion of the washout period, participants began a 10-week online dietary and lifestyle
intervention,which consisted of a six-week process of food elimination, the addition of nutrient-dense
foods, and a focus on lifestyle modifications, followed by a four-week maintenance phase (during which no
food group reintroductions were allowed), using the “SAD (Standard American Diet) to AIP in SIX” group
health coaching program. Food eliminations, additions, and lifestyle modifications were done in weekly
stages. Foods eliminated included all grains, legumes, nightshades, dairy, eggs, coffee, alcohol, nuts, seeds,
refined/ultra-processed sugars, oils, and food additives. Micronutrient-dense food additions included foods
rich in mono and polyunsaturated fatty acids, bone broth, seafood, fermented foods, and organ meats.
Lifestyle modifications included the promotion of support systems, sleep hygiene, stress management,
movement, and increasing time spent outdoors.
Certified health coaches and NTPs led the dietary and lifestyle intervention, educating participants with
reasons for food eliminations, additions, and particular lifestyle modifications. They provided plans to help
participants sustain the rigorous elimination process such as menu planning, grocery shopping, cooking
foods, and recipe guides. All of the education and support was provided virtually via email and a private
Facebook group accessible only to invited members. The health coaches and NTPs led daily discussions on
thechangesparticipants were implementing, provided encouragement when participants faced challenges,
answered questions regarding the study process, and troubleshot with participants who experienced
difficulty with the protocol.
For the purposes of the study, the health coaches and NTPs also collaborated with the lead physician in the
event of any medical concerns for study participants. Through lab testing, FFQ, MSQ, and SF-36, the
physician was able to recognize specific issues that individual participants were experiencing and met with
health coaches to discuss methods of addressing the issues within the study framework. Where appropriate,
the lead health coach and physician discussed with individual participants regarding any concerns and
helped the participant address them effectively.
At the end of the intervention, questionnaires and all laboratory work, including organic acid and stool
samples, were repeated. The study was conducted in full accordance with the Valley Health Research Policies
and Procedures and all applicable Federal and State laws and regulations, including 45 CFR 46, 21 CFR parts
50, 54, 312, 314, and 812, as well as the Good Clinical Practice: Consolidated Guideline approved by the
International Conference onHarmonisation. Participants were allowed to drop out of the study at any time.
Data collection, analysis, and outcomes
A per-protocol analysis was conducted using data from participants completing the study in its entirety (n =
16). Individuals (n = 2) who decreased thyroid medications during the study were not included in the final
group analyses of thyroid hormone parameters but were included in the analyses of thyroid antibodies,
including TPO antibodies and TGA. Individuals (n = 2) who were acutely ill during either the pre-
intervention or the post-intervention laboratory testing were not included in the final group analyses of
thyroid hormone parameters, thyroid antibodies, hs-CRP, white blood cell (WBC) count, or differential cell
count analysis. Data from all 17 participants completing pre-intervention testing and 16 participants
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 3 of 33
completing post-intervention testing are included in the Appendix. Specific denotations are listed in the
Appendix to designate the specific data described above that was not included in the respective per protocol
analyses as well as significant outlying data that was not included in the post-hoc secondary analyses.
Paired t-tests were calculated for all SF-36, MSQ, thyroid parameters, including antibodies, WBC count,
differential cell counts, hs-CRP, self-reported weight, and BMI results from pre- to post-dietary intervention
using Prism 8 (GraphPad Software, CA, US), resulting in a total of 27 tested parameters. It was noted during
initial statistical calculations that several individual subscales of the SF-36 failed the Shapiro Wilk test for
normality, and thus, all SF-36 data sets could not be assumed to be normally distributed. Wilcoxon Signed-
Rank tests were thus performed for all eight subscales of the SF-36, and the respective median values were
calculated and recorded alongside the respective inter-quartile range (IQR). All other data sets were
assumed to be normally distributed, with statistics from the resulting paired t-tests represented as a mean
(M) and standard deviation (SD). Effect sizes for normally distributed samples were also calculated using
Hedge's g statistic (g) and are listed when appropriate.
In order to correct for error when performing statistical analyses for multiple hypotheses, balancing the risk
of creating both Type I and Type II errors, the study authors utilized a false discovery rate control
adjustment outlined by Glickman, Rao, and Schultz with a maximum false discovery rate d = 0.05 for n = 27
statistical tests. As part of this adjustment, new thresholds for statistical significance were set and are listed
with their originally calculated and corresponding p-value in the Appendix [20].
The study's primary outcome was a significant change in SF-36 measures. The study's secondary outcomes
consisted of changes in clinical symptom burden as measured by the MSQ, changes in thyroid parameters,
including thyroid antibodies, changes in WBC and differential cell counts, and changes inhs-CRP. Measures
from the organic acid and stool testing were exploratory in nature, however, pre-intervention data from
these tests were utilized to inform specific dietary recommendations for individuals during week five of the
intervention. These recommendations varied and were based on aspects of the organic acid test suggesting
deficits in B vitamins or minerals such as magnesium, copper, riboflavin, B6, folate, or B12 as well as aspects
of the stool testing suggesting overgrowth of bacterial organisms, fat malabsorption, or pancreatic
insufficiency. Clinically relevant specifics of the stool and organic acid testing from individuals pre and post-
intervention, as well as clinical recommendations provided midway through the 10-week intervention, are
discussed as part of participant case summaries in the Appendix. Adverse effects were monitored
throughout the study and recorded.
Results
Seventeen women meeting the study’s inclusion and exclusion criteria were enrolled and completed the
two-week washout period. Baseline demographics, including age, height, weight, BMI, and ethnicity, are
listed in Table 1. Fifteen out of 17 (87.5%) of the women were noted to be Caucasian. One participant became
pregnant during the study and, as a result, discontinued participation in the study and was not included in
the final analysis.
Variable N Mean (SD)
Age, y 16 35.6(5.7)
Height (in) 16 65.3(2.4)
Weight (lbs) 16 149.5(19.5)
BMI 16 24.9(2.6)
TABLE 1: Baseline demographics of participants included for final analysis
y (years), in (inches), lbs (pounds), BMI (bod y mass index), SD (standard deviation), N ( sample size)
Sixteen women (n = 16) completed the SF-36 and MSQ before and after the 10-week program. There was a
statistically significant improvement in HRQL as measured by all eight subscales of the SF-36 (Table 2) with
the most marked improvements noted in the physical role functioning subscale with a pre-intervention
median = 25, IQR 88, and post-intervention median = 100, IQR 50 (p = 0.001), the vitality subscale with a
pre-intervention median = 23, IQR 19, and post-intervention median = 58, IQR 34, p < 0.0001, and the
general health subscale with a pre-intervention median = 40, IQR 26, and post-intervention median = 70,
IQR 35 (p < 0.0001)
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 4 of 33
SF-36 Physical
Functioning
SF-36 Physical
Role Functioning
SF-36 Emotional
Role Functioning
SF-36
Vitality
SF-36
Mental
Health
SF-36 Social
Role
Functioning
SF-36
Bodily
Pain
SF-36
General
Health
N 16 16 16 16 16 16 16 16
Median (IQR)
Pre 80 (29) 25 (88) 33 (92) 23 (19) 54 (25) 63 (22) 68 (22) 40 (26)
Median (IQR)
Post 95 (10) 100 (50) 78 (19) 58 (34) 78 (19) 81 (22) 78 (21) 70 (35)
Median of
Differences
(IQR)
10 (10) 50 (75) 41 (67) 33 (29) 22 (12) 19 (37) 23 (32) 28 (21)
P 0.0001* 0.001* 0.0063* <0.0001* <0.0001* 0.0057* 0.0112* <0.0001*
TABLE 2: SF-36 paired t-tests results and statistics
SF-36 (36-Item Short Form Health Survey), Pre (pre-intervention), Post (post-intervention ), N (sample size), IQR (inter-quartile range) , P (p value), (*)
denotes statistically significant p value
Figure 1 displays a scatter plot of SF-36 Physical Role Functioning scores pre- and post-intervention.
Individual pre-intervention scores are depicted with circles and individual post-intervention scores are
depicted with triangles. Error bars indicate the inter-quartile range (IQR). Solid, bolded vertical lines within
the IQR indicate the median.
FIGURE 1: SF-36 physical role functioning scores pre- and post-
intervention
SF-36 (36-Item Short Form Health Survey), PRF (physical role functioning), Pre (pre-inte rvention), Post (post-
intervention)
Figure 2 displays a scatter plot of SF-36 physical functioning scores pre- and post-intervention. Individual
pre-intervention scores are depicted with circles and individual post-intervention scores are depicted with
triangles. Error bars indicate the inter-quartile range (IQR). Solid, bolded vertical lines within the IQR
indicate the median.
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 5 of 33
FIGURE 2: SF-36 physical functioning scores pre- and post-intervention
SF-36 (36-Item Short Form Health Survey), PF (physical functioning), Pre (pre-interventi on), Post (post-
intervention)
Figure 3 displays a scatter plot of SF-36 vitality scores pre- and post-intervention. Individual pre-
intervention scores are depicted with circles and individual post-intervention scores are depicted with
triangles. Error bars indicate the inter-quartile range (IQR). Solid, bolded vertical lines within the IQR
indicate the median.
FIGURE 3: SF-36 vitality scores pre- and post-intervention
SF-36 (36-Item Short Form Health Survey), Pre (pre-intervention), Post (post-intervention )
Figure 4 displays a scatter plot of SF-36 general health scores pre- and post-intervention. Individual pre-
intervention scores are depicted with circles and individual post-intervention scores are depicted with
triangles. Error bars indicate the inter-quartile range (IQR). Solid, bolded vertical lines within the IQR
indicate the median.
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 6 of 33
FIGURE 4: SF-36 general health scores pre- and post-intervention
SF-36 (36-Item Short Form Health Survey), Gen. Health (general health), Pre (pre-interve ntion), Post (post-
intervention)
The clinical symptom burden as determined by MSQ (Figure 5), which measures symptoms over a four-week
period, decreased significantly from pre-intervention (M = 92, SD 25) to post-intervention (M = 29, SD 20), n
= 16, t(15) = 9.3, p < 0.0001 with a large effect size (g = 2.81).
FIGURE 5: MSQ scores pre-intervention to post-intervention
MSQ (Medical Symptoms Questionnaire), Pre (pre-intervention), Post (post-intervention ), SD (standard
deviation), error bars indicate SD
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 7 of 33
Inflammation, as measured byhs-CRP (Figure 6), decreased significantly from pre-intervention (M = 1.63
mg/L, SD 1.72) to post-intervention (M = 1.15 mg/L, SD 1.31), n = 14, t(13) = 2.60, p = 0.0219 with a small
effect size (g = 0.302). As previously noted, data from two participants who were acutely sick during either
the pre- or post-intervention blood chemistry testing were not included in the final analysis for hs-CRP.
FIGURE 6: Serum hs-CRP from pre-intervention to post-intervention
hs-CRP (high sensitivity C-reactive protein ), Pre (pre-intervention), Post (post-interventi on), SD (standard
deviation), error bars indicate SD
It was additionally noted when performing the statistical analysis that one participant had a significantly
elevated hs-CRP both pre-and post-intervention when compared to the pre- and post-intervention group
means, however, she was not acutely sick during either the pre- or post-intervention blood chemistry
testing. While the participant’s hs-CRP was noted to decrease from pre- to post-intervention, her data still
remained a significant outlier from the group mean as seen in the previous scatter plot (Figure 6). A post-hoc
secondary analysis was conducted removing the statistical outlier, resulting in a sample size of n = 13, a pre-
intervention mean, M = 1.22 mg/L, SD 0.81, and post-intervention mean, M = 0.85 mg/L, SD 0.72, t(12) =
2.34, p = 0.037 with a moderate effect size (g = 0.473). The pre- and post-intervention hs-CRP data tables in
the Appendix denote the specific data from the two acutely sick individuals described above that was not
included in the final analysis as well as the data from the outlier that was not included in the post-hoc
secondary analysis.
Pre- and post-statistics for all thyroid markers, including antibodies, are listed in Table 3. Individuals who
decreased medication use following initial laboratory testing or during the course of the study (n = 2), as
described previously in the methods, were not included in the final analysis. Additionally, data from the two
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 8 of 33
participants (n = 2) who were acutely sick during the pre- or post-intervention thyroid testing were not
included in the final analysis for TSH, free T4 and T3, total T3 and T4, and reverse T3. Data regarding
antibody levels, however, for these two participants were included in the final data analysis. This resulted in
a total of 12 participants analyzed for thyroid markers and 14 analyzed for thyroid antibodies. All data for
the 17 participants completing pre-intervention thyroid testing as well as the 16 participants completing
post-intervention thyroid testing is listed in the Appendix with specific denotations for the individual data
described above that was not included in the final data analysis.
TSH
(μIU/mL)
Total T3
(ng/dL)
Free T3
(pg/mL)
Reverse T3
(ng/dL)
Total T4
(μg/dL)
Free T4
(ng/dL)
TPO
(IU/mL)
TGA
(IU/mL)
N 12 12 12 12 12 12 14 14
Mean (SD)
pre 2.02(1.46) 97.3(18.0) 2.4(0.6) 17.4(4.3) 7.0(1.1) 1.3(0.4) 225(178) 110(261)
Mean (SD)
post 1.98(1.44) 89.0(9.0) 2.4(0.5) 19.1 (5.3) 7.1(1.4) 1.4(0.4) 219(186) 124(293)
t 0.075 1.668 0.1515 1.9717 0.5932 0.841 0.7703 1.4292
P 0.942 0.124 0.882 0.0743 0.565 0.418 0.455 0.176
g 0.029 0.584 0.029 0.355 0.124 0.099 0.035 0.0532
TABLE 3: Thyroid hormone and antibody values pre- and post-intervention with paired t-test
statistics
TPO (thyroid peroxidase antibodies), TGA (anti-thyroglobulin antibodies), pre (pre-intervention), post (post-intervention), N (sample size), SD (standard
deviation), t (t-test statistic), P (p-value), g (He dges' g)
No clinically nor statistically significant changes were seen in TSH, total T3 or T4, and free T3 or T4.
Additionally, no clinically nor statistically significant changes were noted for either TPO antibodies or TGA.
White blood cell (WBC) and differential cell counts pre- and post-intervention are listed in Table 4. It was
noted that there was a decrease in mean WBC count from a pre-intervention mean of 5.6 x 103 / μL (SD 1.4)
to a post-intervention mean of 5.1 x 103/μL (SD 1.4) that did not reach statistical significance, p = 0.1396. As
previously noted, two out of the 16 individuals completing the pre- and post-intervention blood chemistry
were noted to be acutely sick during either the pre- or post-intervention laboratory testing period and could
not be included in the final analysis.
WBC (103/μL) Neutrophils (%) Lymphocytes (%) Monocytes (%) Eosinophils (%)
N 14 14 14 14 14
Mean (SD) Pre 5.6(1.4) 57.9(6.6) 30.8(5.3) 8.4(2.3) 2.4(1.6)
Mean (SD) Post 5.1(1.4) 55.9(8.2) 34.0(7.3) 7.4(1.3) 2.1(1.4)
P 0.1396 0.183 0.0286 0.0684 0.385
g 0.311 0.268 0.502 0.535 0.199
TABLE 4: WBC and differential cell counts pre- and post-intervention with paired t-test statistics
WBC (white blood cell), Pre (pre-intervention ), Post (post-intervention), N (sample size), SD (standard deviation), t (t-test statistic), P (p -value), g (Hedges'
g)
Figure 7 displays a box plot depicting WBC counts both pre- and post-intervention as well as the mean WBC
count with SD. It was noted when performing the paired t-test statistics and creating the box plot that one
individual was a significant outlier when compared to the group mean difference in WBC count with an
increase in WBC from 6.3 x 103/μL pre-intervention to 8.4 x 10 3/μL post-intervention. The box plot also
depicts two participants who began the intervention with low or borderline low WBC counts (normal > 3.3 x
103/μL) and had increases in WBC count at post-intervention trending toward the group post-intervention
mean.
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 9 of 33
FIGURE 7: WBC count pre- and post-intervention
WBC (white blood cell), Pre (pre-intervention ), Post (post-intervention), error bars indicate SD
Statistically significant changes were seen in weight (M = 143.4 lbs, SD 16.7, p = 0.002) and BMI (M = 23.9,
SD 2.2, p = 0.002) from baseline to post-intervention (Table 5).
Weight (lbs) BMI
N 16 16
Mean (SD) Pre 149.5(19.5) 24.9(2.6)
Mean (SD) Post 143.4(16.7) 23.9(2.2)
P 0.002* 0.002*
TABLE 5: Weight and BMI of all participants pre- and post-intervention, (*) denotes statistically
significant P value (p < 0.05)
BMI (body mass index), lbs (pounds), N (sa mple size), SD (standard deviation), Pre (pr e-intervention), Post (post-intervention), P (p- value)
These results remained significant when a subgroup analysis was performed on participants with a baseline
BMI ≥ 25 (M = 27.1, SD 1.0) to post intervention (M = 25.8, SD 1.0, p = 0.011) (Table 6).
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 10 of 33
Weight (lbs) BMI
N 8 8
Mean (SD) Pre 163.0(19.1) 27.1(1.0)
Mean (SD) Post 155.1(15.3) 25.8(1.0)
P 0.011* 0.011*
TABLE 6: Weight and BMI of overweight subjects (24.9 < BMI < 29.9) pre- and post-intervention, (*)
denotes statistically significant P value (p < 0.05)
BMI (body mass index), lbs (pounds), N (sa mple size), SD (standard deviation), Pre (pr e-intervention), Post (post-intervention), P (p- value)
It should be noted that the review of the individual FFQs was used to determine qualitative and
compositional changes in dietary habits with regards to eliminated foods as part of AIP and was not used to
determine portion sizes or total caloric intake.
Six out of the 13 women beginning the study on thyroid replacement medication decreased their dose of
hormone replacement medication after the 10-week intervention. All three individuals who decreased the
dosages of their medication following the pre-intervention testing made subsequent decreases in their
medication dosage in addition to three individuals who decreased their medication dosages following post-
intervention laboratory testing. All three of the women who began the study without the use of hormone
replacement medication continued without the use of replacement medication as of the final post-
intervention study visit.
There were no moderate to severe adverse effects noted during the duration of the study. Some study
participants reported mental challenges during the initial phases of the dietary eliminations, however, this is
was offset very quickly by decreases in overall symptom burden.
Discussion
This single-arm pilot study adds to the current evidence that AIP, a modification of the Paleolithic diet
involving the elimination and promotion of certain foods, may help alleviate symptoms and improve quality
of life in participants with an autoimmune disease. We demonstrated preliminary efficacy in participants
with HT, via statistically and clinically significant improvements in SF-36 and MSQ scores, as well as
statistically and clinically significant decreases in hs-CRP, weight, and BMI despite no statistically
significant changes in thyroid laboratory markers or thyroid antibodies. Reviews of FFQs from participants
during the 10-week program revealed 95%-100% adherence to the strict elimination criteria. The strict
dietary adherence is most likely a result of the intensive health coaching and community-based structure
providing both education and a source of communal accountability. Preliminary study questionnaires
revealed a majority of the participants reporting familiarity with AIP. Some participants even reported
previous attempts at the AIP dietary protocol for fewer than five days, given the lack of education about the
dietary approach, support services, and communal accountability as well as the overall challenge in
preparing 100% AIP-compliant meals. The role of the physician, health coaches, and NTPs, as well as the
participants’ communal group environment, cannot be understated and appears to be the primary mediating
elements behind the high rate of adherence.
These results additionally suggest that the AIP diet and concomitant lifestyle modification, as implemented
by a multi-disciplinary team, can be safely used as adjunctive treatments for people with HT who are already
utilizing hormone replacement therapy. There were no reported serious adverse effects, with many
participants actually reporting noticeable positive changes within the first four weeks of the elimination
diet. While there were no observed changes in mean thyroid laboratory markers and antibodies, six out of 13
women (46.1%) who were taking thyroid replacement medication at the beginning of the study actually
decreased their dosage of hormone replacement medication by the end of the 10-week study period. All
three women who were asked to decrease or alter their medication dosing at the beginning of the study due
to pre-intervention laboratory findings of low TSH or abnormal free hormone levels actually found they
needed to decrease their medications even further following the 10-week program. Three women who began
the study without the utilization of hormone replacement medication were able to continue without
hormone replacement medication. One individual who enrolled with subclinical hypothyroidism and
elevated thyroid antibodies diagnostic of HT had a significantly higher post-intervention TSH, yet nearly
identical free and total hormone levels as well as lower TPO antibodies at post-intervention. It is difficult to
predict the continued disease course of this specific individual outside of the study structure, however, it is
likely that she would require both hormonal replacement therapy with concomitant dietary and lifestyle
support to manage any further progression of autoimmune thyroiditis.
Despite the lack of a significant clinical change in mean thyroid markers, including antibodies, the
statistically and clinically significant decreases observed for hs-CRP point to modulation of the overall
immune and inflammatory response underlying autoimmune thyroiditis. Additionally, a secondary post-hoc
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 11 of 33
analysis of changes in WBC count from pre- to post-intervention (n = 13) that removed one statistical outlier
resulted in a statistically significant change in mean WBC count from 5.5 x 10 3/μL (SD 1.4) to 4.9 x 103/μL
(SD 1.1), p = 0.0205. There was also a noted increase in mean lymphocyte count from pre- to post-
intervention (p = 0.0286) that could not be assumed to be statistically significant after correcting for
multiple hypothesis testing using the false discovery rate correction. It is clear from these
statistical examinations that there is some underlying modulation of the immune system that is not as
statistically or clinically robust as the changes in HRQL and clinical symptom burden but, nonetheless,
should be acknowledged and explored in further study of the AIP dietary intervention. It is also interesting
to note that the pre-intervention mean hs-CRP in the post-hoc secondary analysis that included n = 13
subjects was classified as intermediate risk while the post-intervention mean actually dropped below 1.0
mg/L into low-risk categorization.
The authors speculate that it is possible that one would observe an eventual decrease in thyroid antibodies
and a decreased need for supplemental medication as well as more robust changes in immune and
inflammatory markers in participants adhering to the AIP dietary principles for additional periods of six to
12 months.
In speculating as to the mechanisms behind the observed positive changes in quality of life, symptom
burden, as well as hs-CRP, we suggest a further examination of the original criteria set forth for a feasible
and efficacious dietary and lifestyle intervention. Self-reported FFQs and dietary journals provided
throughout the duration of the study indicate the inclusion of foods with greater nutrient density by all
participants and the exclusion of less nutrient-dense foods. Qualitative post-intervention surveys
additionally appear to indicate that the study participants received a positive benefit from the gradual nature
of the dietary eliminations, the consistent support from the multi-disciplinary team, and the ability to
interact with other participants making the same dietary and lifestyle changes. There was a statistically and
clinically significant change in weight and BMI from pre- to post-intervention within both the cohort as well
as a smaller overweight subpopulation. Despite the dietary intervention lacking a focus on caloric
quantification, the restriction of specific macronutrients, such as carbohydrates or fats, or an emphasis on
the promotion of weight loss, individuals indicated self-reported weight loss from pre- to post-intervention
that likely contributed to improvements in HRQL and symptom burden.
While the study program is inherently confounded due to its multi-faceted design, including social support,
lifestyle education, medical supervision, and dietary guidance, the profound improvements observed in the
quality of life and symptom burden seem to indicate a synergistic and compounding benefit from the
inclusion of multiple therapeutic elements.
There are currently no published studies assessing the utilization of a comprehensive dietary and lifestyle
intervention in participants with HT, making it difficult to provide an analysis of comparative or expected
treatment effects. Winther et al. assessed the role of thyroxine treatment over a six-month period to
improve quality of life in a population of 78 individuals newly diagnosed with HT and either subclinical
hypothyroidism (4 µIU/mL < TSH < 10 µIU/mL), n = 66, or overt hypothyroidism (TSH > 10 µIU/mL ), n = 12
[3]. The authors noted that despite optimal medical management over the six-month period, only the SF-36
subscales of vitality, physical role functioning, and mental health showed statistically significant changes
[3]. When examining the data from the 58 participants completing the six-month study, it should be noted
that the increases in these three domains ranged from only 3%-8%, correlating to a minimal effect size as
well as a potentially insignificant change in clinical status [3].
While we cannot compare SF-36 statistics from the AIP intervention directly with those from Winther et al.,
as we could not assume all SF 36 subscale data sets from the AIP intervention to be normally distributed and
thus could not accurately calculate respective means and SDs, it is worth examining some of the more
notable pre- to post-intervention changes for specific SF-36 subscales between the AIP intervention and
the study group from Winther et al.
In examining the relative magnitude of changes for the SF-36 subscales: physical role functioning, vitality,
mental health, and general health from the current intervention, the study authors observed a remarkable
increase in physical role functioning scores from a median of 25, IQR 88, pre-intervention to a post-
intervention median of 100, IQR 50, corresponding to a median difference of 50, IQR 75. Similar large-
magnitude changes were noted when examining median values pre- and post-intervention for the vitality,
mental health, and general health subscales. The pre-intervention median vitality subscale score was noted
to be 23, IQR 19, however, post-intervention, the median vitality subscale score increased to 58, IQR 34,
with a median difference of 33, IQR 29. The pre-intervention median mental health subscale score was
noted to be 54, IQR 25, however, post-intervention, the median mental health subscale score increased to
78, IQR 19, with a median difference of 22, IQR 12. The pre-intervention median general health subscale
score was noted to be 40, IQR 26, however, post-intervention, the median general health subscale score
increased to 70, IQR 35, with a median difference of 28, IQR 21.
When comparing the magnitude of change noted for these three SF-36 subscales between the study from
Winther et al. and the AIP intervention, it is important, first, to note the small and underpowered sample
size of the AIP study. Additionally, the vitality subscale scores in the AIP trial at baseline were lower when
compared to the baseline scores of participants in the Winther et al. trial, with both study populations
becoming clinically equivalent post-intervention.
Mental health scores in this trial at baseline were clinically similar to those of Winther et al. (AIP pre-
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 12 of 33
intervention median = 54, IQR 25; Winter et al. pre-intervention mean = 47 (SD 9), however, at post-
intervention, there was a marked difference between these two study groups with the median mental health
score post-intervention from the AIP study being equal to 78 (IQR 19) while the mean mental health score
post-intervention from the Winther et al. trial was 50 (SD 10) [3] . When comparing the other SF-36 domains,
greater improvements were also seen in the physical functioning, bodily pain, emotional role functioning,
and social role functioning scales for participants in the AIP trial as compared to those in the Winther et al.
trial [3].
In examining the bodily pain SF-36 subscale in the AIP trial, there was a notable increase from a pre-
intervention median of 68 (IQR 22) to 78 (21) at post-intervention (p = 0.0112) as compared to Winther et
al.: 52 (SD 12) pre-intervention to 55 (SD 10), p > 0.05 following six months of levothyroxine therapy [3]. In
reviewing the specific subscales of the MSQ, it appeared that the improvements seen in bodily pain as
measured by the SF-36 were primarily related to improvements in joint pain, muscle aches, and headaches as
indicated more specifically by scores from the MSQ. Given the current concerns surrounding opioid
misuse/overuse in those suffering from chronic pain conditions, including individuals with HT, multi-
dimensional, non-pharmacologic interventions, such as the AIP dietary and lifestyle intervention utilized in
this trial, may provide clinicians with novel, efficacious, and low-risk treatments for chronic pain.
Improvements in quality of life and symptom burden may be of critical benefit for both patients and
clinicians, as it may help increase trust in providers as well as adherence to continued medical and lifestyle
therapy. Despite prior work indicating that quality of lifecould be negativelyimpacted by restrictive diets,
this study suggests that quality of life was not negatively impacted but markedly enhanced [10].
The reason for our conflicting findings regarding changes in quality of life, as previously suggested, may be
due to the AIP study’s multi-dimensional treatment design involving frequent monitoring and interactions
between participants with the team of health coaches and NTPs via a private Facebook group. Research on
cancer survivors has shown preliminary evidence linking increased fruit and vegetable intake to increased
social support as well as feelings of hope, possibly indicating a mechanism by which social support alone can
improve one’s overall food choices [21].
Additional research indicates a strong association between a person’s quantity and quality of social
interactions and their perceived health and quality of life [22]. It is unlikely, however, that given the
profound improvements in the physical role functioning as well as vitality and general health subscales of
the SF-36 that social interaction alone, whether between study participants themselves or between study
participants and the multi-disciplinary team could account for all of the observed improvements in quality
of life as well as overall symptom burden.
Limitations to the study include its small sample size, the lack of a control group, the lack of blinding, the
possibility for selection bias of participants enrolling in the study, as well as response bias from participants
regarding their weights. Additional limitations include the use of a medical symptoms questionnaire that
has yet to be validated in large populations as well as the potentially transient nature of the participant’s
symptoms being documented by the questionnaire. Further limitations to this study include the lack of data
collection on physical activity, sleep, social support, stress management, or the effect that eliminated foods
would have had if they were to be reintroduced systematically.
Conclusions
Our pilot study suggests that an online, community-based AIP diet and lifestyle program facilitated by a
multi-disciplinary team can significantly improveHRQLand symptom burden in middle-aged female
subjects with HT. While there were no statistically significant changes noted in thyroid function or thyroid
antibodies, the study’s findings suggest that AIP may decrease systemic inflammation and modulate the
immune system, as evidenced bythedecreases in averagehs-CRP. Dietary and lifestyle changes may be a
significant life stressor, but the use of health coaches and NTPs, in addition to nutritionally trained
physicians, may offset this and provide an increase in quality of life. Larger randomized controlled trials are
necessary to validate these findings and examine long-term follow-up, adherence, and any adverse events
during the elimination and/or maintenance phase of AIP. Given the low-risk nature of the AIP dietary and
lifestyle intervention as well as the improvements seen in HRQL and the participants’ symptom burden,
further study in larger populations of individuals with HT implementing AIP as part of a multi-disciplinary
diet and lifestyle program is warranted.
Appendices
Case summariesand exploratory analyses
Case 1
Case 1 involved a29-year-oldfemale with a past medical history of chronic rhinosinusitis. She was on
multiple anti-inflammatory and allergy medications in addition to T4 and T3 therapy. She sought to adopt
sustainable dietary, exercise, and stress management practices from participating in the study. She enrolled
with a very high symptom burden (MSQ = 126) with the worst symptoms related to chronic rhinosinusitis,
dermatological, musculoskeletal, and gastrointestinal systems. Her complaints specifically consisted of
acne, dry skin, hair loss, joint and muscle aches, belching, bloating, and alterations in bowel habits,
including constipation and diarrhea. She additionally complained of excessive weight, food cravings,
compulsive eating, as well as cognitive and mood concerns with poor concentration, poor memory, anxiety,
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 13 of 33
and depressed mood. Her initial FFQ revealed dietary patterns consisting of gluten-free refined products,
refined potatoes, a variety of fruits, vegetables, processed and unprocessed meats, and dairy substitute
products. She endorsed a predilection and craving for carbohydrate-rich foods.
Initial laboratory findings were skewed and invalid, as the participant was actively sick with an acute on
chronic sinus infection. She was taking antibiotic medications at the time of the laboratory evaluation,
however, there was some concern that the participant was possibly overmedicated with a suppressed TSH
and elevated T4 and T3. The use of urinary organic acid testing revealed an increased need for vitamin B
supplementation, most noticeably folate, as suggested by elevatedformiminoglutamic acid (FIGLU) [23]. The
participant also had a significantly elevated plasma copper.Stool testing revealed decreased short-chain
fatty acids (SCFAs), most noticeably butyrate.SCFAs consist primarily of acetate, butyrate, and propionate,
which are physiologically active byproducts produced via the fermentation of soluble dietary fibers and
resistant starches by commensal bacteria throughout the colon [24]. Their concentrations vary along the
length of the gastrointestinal tract with the highest levels in the cecum and proximal colon [24]. Butyrate
acts as a fuel source for colonic enterocytes, with immune modulating properties through histone
deacetylase inhibition, allowing for the suppression of macrophages and dendritic cells [24].
Additionally, SCFAs have an overall pH-lowering effect on the colon, allowing for the growth of beneficial
bacteria, specifically Lactobacillus and Bifidobacterium [24].
At week six of the program, the participant was counseled to increase the consumption of folate-rich foods,
such as organ meats and leafy greens, and experiment with eliminating foods high in fermentable
oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) for gastrointestinal
symptom relief [25]. She was encouraged to explore whether fermented foods exacerbated her allergy
symptoms. She was instructed to consider lowering her thyroid medication dose given the concerning
elevations found at study onset and to monitor for potential signs and symptoms of hyperthyroidism.
Following theprogram,the participant’s MSQ decreased from 126 to 43, with residual symptoms primarily
related to her continued sinus and allergy complaints. She reported the exacerbation of allergy symptoms
with fermented foods, a 12-pound weight loss, and the start of corticosteroid treatment just prior to final
laboratory testing given another sinus infection. She later notified the medical team of further imaging
revealing an anatomic abnormality of her maxillosinus structure and pursuit of corrective surgery.
A review of her second FFQ documenting the10-weekprogram showed strict adherence to the AIP diet with
the elimination of refined carbohydrates, white potatoes, processed meats, eggs, nuts, grains, and dairy, as
well as increased consumption of unprocessed meat, vegetables, and fruit, and the new inclusion of coconut,
plantains, cassava flour, and maple syrup as the only sweetener.The participant’s exit survey revealed
improvements in sleep, the beginning of an exercise program, and improvements in body composition.
Laboratory testing revealed continued suppressed TSH with elevated total and free T4. The participant
notified the team that she had previously decreased her thyroid medication, Synthroid, from 112 mcg to 100
mcg at week six followed by a further decrease to 88 mcg just prior to her final interview at week 10. She
reported still experiencing signs concerning for hyperthyroidism and was planning to pursue an additional
decrease in medication in conjunction with further treatment for chronic sinusitis.
Review of repeat nutritional testing showed stable, but continued, elevation in her FIGLU as well as plasma
copper. Repeat stool testing showed continued low SCFAs.
Case2
Case2involved a41-year-oldfemale with a history ofdepression,the use of selective serotonin reuptake
inhibitor (SSRI)medication, andT4/T3 therapy. Her goals were to loseweight, improve food cravings, improve
energy, and adopt a healthier lifestyleas a result of the study program. She entered the program with an MSQ
of 98. Her worst symptomsaffected the head, ears, eyes, nose, throat (HEENT), dermatological,
musculoskeletal, neuropsychological, andgenitourinary (GU) systems. More specifically, she complained
ofexcessive mucus production in her pharynx, throat irritation,dry skin, hair loss,hyperhidrosis,jointaches
and stiffness, anxiety, mood swings, irritability, excessive weight gain, food cravings, and compulsiveand
bingeeating behaviors. Her initial FFQ revealed a diet consisting ofrefinedgrainproducts, refined potatoes, a
variety of fruits, vegetables,regularprocessed and unprocessed meats,dairy, andeggs. She reported cravings
for carbohydrate-rich foodsand the regular consumption of sugar-sweetened soda beverages.
Initial laboratory findingsrevealed an elevated TSH at 4.75μIU/mLandhs-CRP of 6.97mg/L. Initial organic
acid nutritional testing showed elevatedsubericand adipic acids as well as an increased need for multiple B
vitamins, most noticeablyriboflavinas suggested by elevatedglutaric acid [26]. Red blood cell (RBC) analysis
for polyunsaturated fatty acid (PUFA) composition revealed elevations in omega-6 fatty acids and the low
end of normal omega-3 fatty acids, resulting in a disturbed omega-3:omega-6 ratio. Stool testing revealed
no pathogenic organisms, however, there was evidence of lipid malabsorption as measured by fecal
phospholipids and cholesterol.
At week six of the program, the participant was counseled to increase the consumptionof fish rich in omega-
3 fatty acids,folate-rich foods,as wellas glycine-rich foods such as bone broth.She was encouraged to
explorethe use of AIP-complaint digestive bitters to assist in the digestion and absorption of nutrients [27].
Following theprogram,the participant’s MSQ decreased from98to12withno further severe symptoms. She
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 14 of 33
reported a 15-pound weight loss, improvements in energy, the cessation of soda consumption, and the
beginning of a formal exercise regimen.
A review of her second FFQ documenting the10-weekprogram showed strict adherence to the AIP diet with
the elimination of refined carbohydrates, potatoes, eggs,legumes, coffee, nuts,seeds,grains, and dairy, as
well as increases in the consumption of unprocessed meat, vegetables, fruit,avocado, and sweet potatoes.
Laboratory testing revealeda decrease in herTSHto 2.34μIU/mL,withotherwise stable hormone levels and
unchanged thyroid antibodies. Herhs-CRP decreased from 6.97 to 5.02mg/L, however, it was noted to be a
significant outlier (despite the decrease) when compared to the group average and was not included in the
post-hoc secondary data analysis.
A review of repeat nutritional testing showedthe improvement and normalization of previously elevated
suberic and adipic acids and the presence of ketone bodies. The participant was noted with a deficiency in
folate as suggested by a markedly elevated FIGLU [23]. The participant saw a decrease in overall omega-6
RBC volume and improved omega-3:omega-6 RBC ratio.Repeat stool testing showed resolved lipid
malabsorption and normalized secretory IgA.
Case3
Case 3 involved a34-year-oldfemale with no significant past medical history. She began the study, taking
only T3 replacement therapy at approximately 5 mcg four to six times daily. She sought to improve her
dietary patterns, removing foods she was sensitive to, improve sleep, as well as begin a formal stress
management program with yoga and meditation. She entered the program with a high MSQ score of 83, with
the worst symptoms affecting the HEENT, dermatological, gastrointestinal, and neuropsychologicalsystems.
More specifically, she complained of dark circles under her eyes, sinus congestion, sneezing, acne,
constipation, bloating, fatigue, lethargy, poor concentration, decreased memory, indecisiveness, depressed
mood, excessive weight gain, food cravings, and behaviors of compulsive and binge eating. Her initial FFQ
revealed a diet consisting of occasional gluten-free products and a variety of fruits, vegetables, potatoes,
unprocessed meats, eggs, and infrequent dairy except for ice cream.
Initial laboratory findings revealed a TSH of 3.55μIU/mLwith low free T4 (fT4 = 0.31 ng/dL). Initial thyroid
peroxidase (TPO) antibodies were 135IU/mLand anti-thyroglobulin antibodies (TGA) were 2.0 IU/mL.Given
these findings, the participant was counseled to begin either T4 only or combination T4/T3 therapy based on
her weight.Initial organic acid nutritional testing showed an increased need for vitamin B6 as suggested by
elevated xanthurenic acid [28]. RBC analysis for PUFA composition revealed elevations in omega-6 fatty
acids, specifically linoleic acid and gamma-linolenic acid, and low normal omega-3 fatty acids, specifically
DPA and DHA. This caused a disturbed omega-3:omega-6 ratio. Stool testing was with microscopic, and
culture analysis revealed rare Blastocystis hominis and an overgrowth of Klebsiellaoxytoca.
At week six of the program, the participant was counseled tocontinue increasing the consumption of omega-
3 fatty fish,organ meats, and foods rich in vitamin B6.Additionally, she was encouraged to explore
theinclusion of fermented foods.
Following theprogram,the participant’s MSQ decreased from83to 10 with no further severe symptoms. She
reported an overall 10-poundweight losswith increasedenergy. She stated she was overall much happier with
the resolution of brain fog as well as gastrointestinal complaints, including bloating, belching, and gas. She
also reported improvements in her skin and acne.
A review of her second FFQ documenting the10-weekprogram revealed strict adherence to the AIP diet with
the elimination of refined carbohydrates, potatoes, eggs, legumes,nuts, seeds, grains, and dairy, as well as
increases in the consumption of unprocessed meat, vegetables, fruit, and avocado, and the new regular
inclusion of coconut products, plantains, homemade liver pate, and bone broth.
Laboratory testing revealed anincrease in TSH to 7.35μIU/mL,however, during the final exit interview, the
participant noted decreasing her use of T3 replacement to only 5 mcg one to two times daily, in addition to
not starting any T4 replacement. An examination of her hormone levels showed an increase of free T4 from
0.31 to 0.77 ng/dL and total T4 from 2.0 to 5.0μg/dL. T3 levels had maintained with the normal range. As the
participant was not taking any replacement T4 and had decreased total T3 replacement use, the authors
speculated that her thyroid began producing increased amounts of T4 due to decreased exogenous
suppression and improvements in endogenous synthesis. The authors additionally speculate that the dietary
intervention, in conjunction with decreased exogenous suppression, contributed to the participant’s
increased T4 levels. As the participant decreased her use of thyroid replacement medications significantly
during the intervention, her thyroid function laboratory datacould not be included in the final data
analysis.It should be noted, however, that the participant’s TGA normalized to <0.9 IU/mL and TPO
antibodies decreased from 135 to 107 IU/mL.
A review of repeat nutritional testing revealed significant improvements in her RBC PUFA, analysis with
increases in RBCeicosapentaenoic acid (EPA), docosapentaenoic acid(DPA), and docosahexaenoic acid (DHA)
and decreases and normalization of RBC linoleic acid and gamma-linolenic acid. Repeat stool testing
showed no overgrowth of pathogenic organisms with no noticeable lipid malabsorption. There was still
overgrowth of additional Klebsiella species but no microscopic visualization ofBlastocystishominis.
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 15 of 33
At the end of the study during the exit interview, given her significant improvements, the participant
informed the study team of her decision to continue her use of Liothyronine 5 mcg one to two times daily
and repeat thyroid testing in three months.
Case 4
Case 4involved a38-year-oldfemale with no additional, significant past medical history who began the study
taking100 mcg of Synthroid.She wanted to improve her diet, sleep,weight, and energy and begin a formal
exercise practice.She entered the program with a moderate symptom burden (MSQ = 55) with the worst
symptoms affecting her dermatological, gastrointestinal, musculoskeletal,and neuropsychologicalsystems.
More specifically, she complained ofacne,hair loss, dry skin, constipation, belching,bloating,joint pain,
stiffness, muscle aches,fatigue, tiredness,lethargy, poor concentration, insomnia, increased weight, food
cravings, compulsive eating, and binge eating. Her initial FFQ revealed a diet consisting of
infrequentgluten-containing products, a variety of fruits, vegetables, regular unprocessedand
processedmeats, eggs, dairy,potatoes, one to three alcoholic beverages weekly, corn-based products, water,
kefir beans, and legumes. Prior to enrollment, she had been taking multiple supplements containing various
vitamins and minerals, a probiotic, occasional fish oil, evening primrose oil, and collagen peptides.
Initial laboratory findings revealed a TSH of2.85μIU/mL, TPO antibodies of 180IU/mL, TGA of603.5 IU/mL,
and a slightly elevated hs-CRP at 2.64 mg/L. Initial organic acid nutritional testing showed balanced
nutritional markers likely related to her previous and ongoing supplementation. RBC analysis for PUFA
composition revealeda high normal omega-6 fatty acidprofile, resulting in a disturbed omega-3:omega-6
ratio. Stool testing showed low normal SCFAs andanovergrowth of Klebsiella pneumonie and Candida
albicans. There was no evidence of lipid malabsorption.
At week six of the program, the participant was counseled to increase consumption of omega-3 fatty fish and
animal protein.She was encouraged to consider including fermented foods and removing foods high in
FODMAP to improve her constellation of gastrointestinal symptoms,including belching, bloating, and
irregular stools [25].
Following theprogram,the participant’s MSQ decreased from55to28withtheonly continued frequent
symptom of hair loss.She reported a 15-poundweight loss with increasedenergy, improved sleep, decreased
food cravings, improved compulsive eating or overeating, and improved cognitive functioning.
A review of her second FFQ documenting the10-weekprogram suggested strict adherence to the AIP diet
with the elimination of refined carbohydrates, potatoes, eggs, legumes, nuts, seeds, grains, and dairy as well
as increases in the consumption of unprocessed meat, vegetables, fruit,and the inclusion of coconut
products,gelatin, collagen, sauerkraut, and kombucha.
Laboratory testing revealed adecreasein her TSH to2.06μIU/mLwithan increase of free T4 from 1.4 to
1.59ng/dL and total T4 from8.3to9.8μg/dL. T3 levels maintained withinthe normal range.Her hs-CRP was
still elevated at 2.90 mg/L withTGA and TPO antibodies also remaining elevated and clinically unchanged.
A review of repeat nutritional testing revealed continued stability in vitamin and mineral markers with
mildimprovements in her RBC PUFA analysis, increased omega-3 RBC volume, and decreased omega-
6RBCvolume. The participant also had elevated ketones related to weight loss and a low carbohydrate
dietary pattern.Repeat stool testing revealed no growth of either K.pneumonieor C. albicans.
Case5
Case 5 involved a26-year-oldfemale with no significant past medical history, who enrolled in the study on
75 mcg of Synthroid. Her primary goal for participating in the program was to conceive a child. She had
reported to the medical team prior to the study that she had been having significant difficulty in becoming
pregnant. Her baseline MSQ was low (MSQ = 37) and was the lowest symptom score of any member of the
study. Initial thyroid testing revealed a normal TSH and thyroid hormone levels with elevations in both TPO
antibodies and TGA. Her hs-CRPwas within normal limits at 0.65 mg/dL. Initial organic acid nutritional
testing revealed no specific vitamin or mineral needs. Stool testing was notable for lipid malabsorption and
low SCFAs.
The participant notified the study team during week eight that she had become pregnant. In conjunction
with the study parameters and at the wishes of the participant, she discontinued participation in the study.
Case6
Case6involved a44-year-oldfemale with no significant past medical history and began the study on 88mcg
ofTirosint.She sought to“feel like herself again,” wanting to improve her mood and energy. She entered the
program with a moderateMSQ (MSQ = 56), with the worst symptoms affecting the gastrointestinal,
musculoskeletal,andneuropsychological systems. Specifically, these complaints consisted of constipation,
belching, bloating, joint pain, stiffness, muscle aches, fatigue, tiredness, lethargy, poor concentration,
comprehension, and memory, anxiety, irritability, mood swings, and headaches. Her initial FFQ revealed a
diet consisting of gluten-free grains,a variety of fruits, vegetables, regular unprocessed meats,
eggs,minimaldairy consumption, potatoes, vegetarian-based soy products, and the regular consumption of
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 16 of 33
lentils,beans, and legumes.She endorsed takingmultiple supplements containing various vitamins and
minerals, fish oil,curcumin, and a flavonoid complex.
Initial laboratory findings revealednormalthyroid function, however, there appeared to be low normal T3
levels and elevated reverse T3, indicating poor T4 to T3 conversion. Herhs-CRP wasnormal at 0.72 mg/L and
TPO antibodies were elevated at 135 IU/mL. TGA was <0.9 IU/mL.Initial organic acid nutritional testing
suggested deficiencies in riboflavin, as suggested by elevated glutaric acid, and vitamin B6, as suggested by
elevated xanthurenate, respectively [26,28]. RBC analysisrevealed a balanced PUFA compositionwith a high
normal omega-3 RBC volume.The participant’s toxin profile revealed a markedly elevated whole blood
mercury at 8.91 mcg/L. During the interview, the participant revealed consuming significant amounts of
seafood and had several amalgam fillings with a history of recent dental work. Stool testingrevealed
lowSCFAsandan overgrowth of Klebsiellaoxytocaand Citrobacter freundii. There was no evidence of lipid
malabsorption; however, there was no measurablefecal secretory IgA.
At week six of the program, the participant was counseled to consume animal protein and organ meats and
increase her intake of vitamin B6-rich foods as well as fermented foods. Following the program, the
participant’s MSQ decreased from 56to33 withan improvement inenergy, headaches, joint pains, and
cognition. She continued to report similar gastrointestinal symptoms of constipation, bloating, and belching
in the setting of an overall excellent rating for her health.
A review of her second FFQ documenting the10-weekprogram showed strict adherence to the AIP diet with
the elimination of refined carbohydrates, potatoes, eggs, legumes, nuts, seeds, grains, and dairy, as well as
increases in the consumption of unprocessed meat, vegetables, and fruit, and the new regular inclusion
ofbone broth andcollagen.
Laboratory testing revealednearly identical values for thyroid function, thyroid antibodies, andhs-CRP, with
no clinically significant changes. There was a decrease in white blood cell (WBC) count from 6.9 x103/µL to
5.9 x 103/µLas well as a decrease in neutrophil percentage from 69% to 59% and increase in lymphocyte
percentage from 21% to 32%.
A review of repeat nutritional testing suggesteda resolution of the riboflavin and vitamin B6 deficiency as
suggested by normalized glutaric acid andxanthurenate [26,28]. Whole blood mercury decreased from an
elevation above 8 mcg/L to within normal limits at 2.56 mcg/L. Repeat stool testingshowed no growth of
either K.oxytocaor C.freundii,anincrease intotal SCFAs, and a normal level of secretory IgA.
Case 7
Case 7 involved a 33-year-oldfemale with a past medical history of dyshidrotic eczema, elevated thyroid
antibodies, including TPO and TGA. She was noted to be euthyroid without the utilization of thyroid
hormone replacement medication prior to enrollment. She wanted to improve stress, improve symptoms in
thyroid autoimmunity while continuing without the use of any thyroid replacement medication, improve
eczema, and find a sustainable dietary template that met her needs. She entered the program with a very
severe symptom burden (MSQ = 114) with the worst symptoms affecting the HEENT, dermatological,
gastrointestinal, musculoskeletal, and neuropsychological systems. More specifically, she complained of
watery eyes, circles under her eyes, hay fever, sinus problems, nasal congestion, frequent throat clearing,
acne, dry skin, rashes, hair loss, constipation, belching, bloating, fatigue, tiredness, lethargy, poor
concentration, confusion, poor memory, anxiety, excessive weight, food cravings, and compulsive binge
eating. Her initial FFQ revealed a diet following a gluten-free and dairy-free template with a variety of
fruits, vegetables, unprocessed and processed meats, eggs, and limitations on starches and potatoes. She was
also taking numerous supplements prior to the study but had recently stabilized on magnesium and fish oil.
Initial laboratory findings revealed a TSH of 1.06μIU/mL, TPO antibodies of 273 IU/mL, TGA of 4.8 IU/mL,
and a normal hs-CRP at 0.43 mg/L. Initial organic acid nutritional testing showed numerous imbalances,
including elevated adipic andsubericacids. The participant had significantly elevated levels of the ketone
body beta-hydroxybutyrate (BHB) likely related to her low carbohydrate consumption. Riboflavin was
deficient, as suggested by elevated glutaric acid [26]. She was otherwise balanced in her additional vitamin
and mineral markers. The participant’s toxic element screen revealed elevated blood mercury at 4.74 mcg/L.
Stool testing revealed additional imbalances, including marked lipid malabsorption, low SCFAs, and an
overgrowth of Klebsiellapneumonieand Citrobacter freundii. Microscopic evaluation also revealed evidence
of trophozoites of Dientamoeba fragilis. Fecal calprotectin and fecal secretory IgA were within normal
limits.
At week six of the program, the participant was counseled to continue with increased consumption of
omega-3 fatty fish, animal protein, and organ meats. She was counseled to take AIP-compliant digestive
bitters to support improved lipid and nutrient absorption [27]. She was counseled on the removal of high
FODMAP-containing foods given her gastrointestinal symptoms, including belching, bloating, and
constipation [25].
Following theprogram,the participant’s MSQ decreased from 114 to 56 with continued eczema and rashes,
despite improvement in acne. Constipation remained despite improvements in bloating and belching. She
reported increased energy, decreased lethargy and apathy, minimal compulsive eating or overeating and
improved cognitive functioning.In continuing discussions with the participant and at the suggestion of the
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 17 of 33
study doctor, she reported secondary evaluations for constipation revealing dyssynergic constipation and
pelvic floor muscular weakness.
A review of her second FFQ documenting the10-weekprogram showed strict adherence to the AIP diet with
the only challenges occurring early in the first few weeks during a 10-day vacation. Laboratory testing
revealed stability in her TSH at 1.13μIU/mL with an increase of free T4 from 1.11 to 1.19 ng/dL and free T3
from 2.2 to 2.5pg/mL.Her hs-CRP remained low at 0.38 mg/L, TGA relatively unchanged at 4.8 IU/mL, and
there was a significant decrease in TPO antibodies from 273 to 190 IU/mL.
A review of repeat nutritional testing revealed continued stability in vitamin and mineral markers with the
normalization of elevated glutaric acid [26], as well as the normalization of previously elevatedsubericand
adipic acids. The participant no longer had elevated ketone bodies, likely related to the inclusion of
additional carbohydrates and certain starches during the program. The previously elevated whole blood
mercury had fallen from 4.74 to 1.79 mcg/L.
Repeat stool testing showed the resolution of previously noted severe lipid malabsorption. There was no
microscopic evidence ofD. fragilis. She was noted to still have low total SCFAs and overgrowth of previously
notedCitrobacterspecies. Fecal calprotectin and fecal secretory IgA remained normal. Upon completion of
the study, the participant continued without the utilization of thyroid hormone replacement.
Case 8
Case 8 involved a33-year-oldfemale with a past medical history of attention deficit hyperactivity disorder
(ADHD) and depression who was recently diagnosed with subclinical hypothyroidism and autoimmune
thyroiditis via elevated TPO antibodies and TGA. She began the study program without the utilization of
thyroid replacement medication. She wanted to improve stress, delay or stop the progression of any thyroid
autoimmunity, continue without the use of any thyroid replacement medication, address poor sleep and low
energy, and improve diet. She entered the program with a very severe symptom burden (MSQ = 108) with the
worst symptoms affecting dermatological, gastrointestinal, musculoskeletal, and neuropsychological
systems. More specifically, she complained of dry skin, flushing, hyperhidrosis, nausea, abdominal pain,
bloating, joint pain, muscle aches, stiffness, fatigue, tiredness, lethargy, poor concentration, confusion, poor
memory, mood swings, irritability, anxiety, excessive weight gain, food cravings, compulsive and binge
eating. Her initial FFQ revealed the intake of chicken, beef, and, occasionally, fish, restrictions on fruit
intake - only berries, a variety of vegetables, grains, potatoes, and some candy and chocolate. She used a
daily B complex as well as magnesium in addition to the prescribed medications Vyvanse, Fluvox and low
dose naltrexone (LDN).
Initial laboratory findings revealed a TSH of 13.45μIU/mL, TPO antibodies of 185 IU/mL, and TGA of 1.8
IU/mL.Her hs-CRP was elevated at 2.59 mg/L and all total and free thyroid hormone levels were within
normal limits. Initial organic acid nutritional testing showed a likely folate deficiency, as suggested by a
markedly elevated FIGLU [25-26]. Plasma copper was high normal at 151.5 mcg/dL. RBC volume of omega-3
fatty acids, including EPA, DPA, and DHA, were within normal limits. Her toxic element screen revealed
elevated whole blood mercury at 4.82 mcg/L, and stool testing revealed an overgrowth of Klebsiella
pneumonie.Fecal calprotectin and fecal secretory IgA were within normal limits.
At week six of the program, the participant was counseled to continue with the previous consumption of
omega-3 fatty fish and increase the intake of various AIP-compliant foods, including animal protein and
organ meats. Additionally,she was encouraged to explore the removal of high FODMAP-containing foods
given her gastrointestinal symptoms, including abdominal pain and bloating [25].
Following theprogram,the participant’s MSQ decreased slightly from 114 to 85, with continued symptoms in
the gastrointestinal, dermatological and musculoskeletal systems despite improvements in acne, bloating,
belching, energy, joint pain, compulsive eating or overeating, and cognitive functioning.
A complete objective analysis of the participant’s health following the program could not be conducted,
however, as she was lost to follow-up, unable to complete her final FFQ, stool, and organic acid testing.
Review of food journals during the study revealed challenges with frequent travel to various social
engagements and consumption of foods outside of the AIP template.
Final laboratory testing was also difficult to interpret, as the participant was acutely ill with an infection as
evidenced by an elevated WBC count, platelets andhs-CRP. In terms of thyroid hormone fluctuations, the
participant’s TSH had risen to 31.92μIU/mL with slight increases in free and total hormones (T3 and T4).
TGA had increased to 4.5 IU/mL, but TPO antibodies had decreased from 185 to 123 IU/mL.As of the final
communication with the participant at the end of the study program, she has not started thyroid
replacement medication.
Case 9
Case 9 involved a36-year-oldfemale with a past medical history of ruptured ovarian cysts, dysmenorrhea
concerning for endometriosis who enrolled in the study on 45 mg of NP thyroid. She wanted to improve
stress, joint pain, fatigue, bloating, IBS-like symptoms, minimize symptom exacerbation during menstrual
cycles, and decrease hair loss. She entered the program with a very severe symptom burden (MSQ = 119)
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 18 of 33
with the worst symptoms affecting the HEENT, dermatological, gastrointestinal, genitourinary,
musculoskeletal, and neuropsychological systems. Specifically, symptoms included headaches, pruritic eyes,
dark circles under her eyes, pruritic ears, otalgia, hay fever, sinus problems, excessive mucus, hair loss,
constipation, belching, bloating, joint pain, stiffness, muscle aches, fatigue, tiredness, poor concentration,
coordination and memory, anxiety, mood swings, irritability, frequent urination, and discharge. Her initial
FFQ revealed a diet low in total animal products with the majority of animal protein coming from eggs and
chicken. She consumed numerous fruits and vegetables, no dairy, minimal gluten consumption with the
majority ofgrain-basedfoods being gluten-free or rice-based. She took magnesium and vitamin D as
supplements and used histamine-2-receptor antagonists as needed for worsening allergic symptoms.
Initial laboratory findings revealed a TSH of 2.79μIU/mL, TPO antibodies of 471 IU/mL, TGA of 3.4 IU/mL,
and hs-CRP within normal limits at 0.76 mg/L. Initial organic acid nutritional testing revealed elevated
adipic acid. RBC analysis of omega-3s was within normal limits due to the regular consumption of fatty fish.
Plasma copper was low at 70.6 mcg/dL and RBC magnesium was also low despite supplementation at 27.8
mcg/g. Vitamin D was noted to be 83.4 ng/dL and the participant was instructed to discontinue the
supplementation of 10,000 IU daily until re-testing in 12 weeks. Her toxic element screen revealed elevated
whole blood mercury at 4.66 mcg/dL.Stool testing revealed low SCFAs and an overgrowth of Citrobacter
species. Fecal calprotectin was normal and fecal secretory IgA was undetectable.
At week six of the program, the participant was counseled to continue with increased consumption of
omega-3 fatty fish and animal protein, including organ meats. She was guided on foods highest in copper
and magnesium. Additionally,she was encouraged to explore the removal of high FODMAP-containing
foods, given her collection of gastrointestinal symptoms, including bloating, abdominal pain, and
constipation [25].She was additionally given education on monitoring allergic symptoms around the intake
of fermented foods.
Following theprogram,the participant’s MSQ decreased dramatically from 119 to 32, with continued
symptoms of painful menstruation and other fluctuations during ovulation. The participant reported
complete elimination of joint pain, as well as anxiety, depressed mood, and impaired cognitive functioning.
Multiple allergic symptoms, including sinus complaints and hay fever, resolved without the use of
medication. She reported increased energy, decreased lethargy and tiredness, as well as resolved frequent
urination and insomnia.
A review of her second FFQ documenting the10-weekprogram showed strict adherence to the AIP diet with
regular consumption of bone broth, organ meats, coconut, and AIP-allowed starches. Laboratory testing
revealed stability in her TSH at 3.06μIU/mL with all total and free hormone remaining in the low normal
ranges. Her hs-CRP remained low and decreased to 0.36 mg/L. TGA remained unchanged at 3.6 IU/mL as did
TPO antibodies measured at 481 IU/mL.
Review of repeat nutritional testing showed improvement in multiple vitamin and mineral markers with
normal levels of all B vitamins. Previously elevated adipic acid had normalized. Plasma copper had increased
into the normal range, however, RBC magnesium still remained unchanged. The previously elevated whole
blood mercury had fallen slightly from 4.74 to inside the normal range at 4.19 mcg/L.
Repeat stool testing showed the normalization of SCFAs. The previous overgrowth of Citrobacter species was
resolved. There was now a detectable and normal level of fecal secretory IgA.
The participant continued following the dietary pattern and increased her thyroid replacement medication
to 60 mg of NP thyroid while seeking further evaluation and support for ongoing menstrual complaints.
Case 10
Case 10 involved a 39-year-old female with a past medical history of mild transaminitis who began the
program on 75 mcg of Levothyroxine and 5 mcg of Liothyronine. Shewanted to improve stress, energy,
bloating, IBS-like symptoms, sleep, and hair loss, and minimize/lower inflammation and lose weight. She
entered the program with a moderate to severe symptom burden (MSQ = 89), with the worst symptoms
affecting the HEENT, dermatological, gastrointestinal, musculoskeletal, and neuropsychological systems.
Specific complaints consisted of headaches, dizziness, pruritic eyes, tinnitus, otalgia, excessive clearing of
throat, sore throat, acne, dry skin, hair loss, diarrhea, constipation, belching, bloating, heartburn, abdominal
pain, joint pain, stiffness, muscle aches, fatigue, tiredness, lethargy, anxiety, mood swings, irritability, and
depressed mood. Her initial FFQ revealed the majority of animal protein coming from chicken and fish,
numerous fruits and vegetables, minimal to no dairy, nut-based dairy substitutes, a mixture of whole grain
and processed grain foods, rice, coffee, and coconut products. She took numerous vitamin and mineral
supplements, including selenium, zinc, magnesium, biotin, iron with vitamin C, B12, and vitamin D.
Initial laboratory findings revealed a TSH of 2.09 μIU/mL, TPO antibodies above the reference range at >600
IU/mL, and TGA at 2.1 IU/mL. Her hs-CRP was elevated at 2.42 mg/L. Initial organic acid nutritional testing
revealed elevated suberic acid. She has elevated FIGLU suggestive of folate deficiency [23] as well as elevated
xanthurenate, suggesting B6 deficiency [28]. RBC analysis of omega-3s was within normal limits and related
to the participant’s regular consumption of fatty fish. Her toxic element screen revealed elevated whole
blood mercury at 7.58 mcg/L and elevated selenium at 427 mcg/L. Upon further questioning, the elevated
selenium may have been caused by 400 mcg of selenium supplementation every day for over a year. She was
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 19 of 33
asked to discontinue supplementation given the concern for toxicity. Her initial blood chemistry revealed an
elevated ALT at 57 IU/L with normal AST at 32 IU/L. Initial stool testing revealed low SCFAs and an
overgrowth of Citrobacter freundii and fungal Geotrichum species. Fecal calprotectin was normal.
At week six of the program, the participant was counseled to continue with increased consumption of
omega-3 fatty fish as well as animal protein, focusing on red meat as well as organ meats. She was educated
on foods highest in copper and magnesium and encouraged to decrease high FODMAP-containing foods
given her gastrointestinal symptoms of bloating, abdominal pain, diarrhea, and constipation [25]. She was
instructed on folate and vitamin B6-rich foods, including organ meats, beef, leafy greens, spinach,
mushrooms, and beets, as well as the use of AIP-compliant bitters to improve digestion [27].
Following the program, the participant’s MSQ decreased dramatically from 89 to 6,with no frequent or
severe symptoms. The participant reported complete elimination of joint pain, anxiety, depressed mood,
irritability, and gastrointestinal symptoms. She reported markedly improved sleep, energy, skin, lethargy,
feelings of soreness, and a 14-pound weight loss.
A review of her second FFQ documenting the 10-week program revealed strict adherence to the AIP diet
with regular consumption of bone broth, organ meats, coconut, and AIP starches. She reported multiple
daily servings of cruciferous and leafy green vegetables and increased intake of animal protein.
Laboratory testing revealed a suppressed TSH at 0.535μIU/mL and the participant reported concern for
overmedication. Her hs-CRP decreased from 2.42 to 0.84 mg/L, TGA decreased slightly from 2.1 to 1.7
IU/mL, TPO antibodies remained above the lab reference range at >600 IU/mL, ALT normalized to 13 IU/L
and AST decreased within the normal range to 16 IU/L.
Repeat nutritional testing revealed marked elevation in ketone bodies likely related to participant’s weight
loss and dietary changes. FIGLU remained elevated, however, xanthurenate had normalized suggesting a
resolved B6 deficiency [28]. Blood selenium remained elevated and previously elevated blood mercury fell
from 7.58 to 6.29 mcg/L. Repeat stool testing revealed resolution of prior Geotrichum yeast overgrowth and
continued overgrowth of C. freundii. The participant continued following the study following the dietary
pattern and chose to decrease her thyroid replacement medication to 50 mcg of levothyroxine.
Case 11
Case 11 involved a 39-year-old female with no significant past medical, who began the program on 75 mcg
of Levothyroxine. Shewanted to decrease stress, improve energy, decrease pain and irritability, and lose
weight. She entered the program with the highest symptom burden of any participant (MSQ = 132), with the
worst symptoms affecting the HEENT, dermatological, cardiac, pulmonary, gastrointestinal, musculoskeletal,
and neuropsychological systems. Specific complaints consisted of headaches, faintness, dizziness, watery
eyes, blurred/tunnel vision, dark circles under her eyes, pruritic ears, ear drainage, stuffy nose, sinus
problems, excessive mucus, sore throat, dry skin, hair loss, flushing, irregular heartbeat, chest congestion,
diarrhea, bloating, abdominal pain, joint pain, stiffness, muscle aches, fatigue, tiredness, lethargy,
restlessness, anxiety, poor concentration, poor memory, mood swings, irritability, depressed mood, and
frequent urination. Her initial FFQ revealed the majority of protein coming from chicken and eggs, with
infrequent fish, red meat, and pork. She consumed numerous fruits and vegetables, regular dairy
consumption, minimal refined grains, with regular whole grain and potato consumption. She took a daily
probiotic and multivitamin.
Initial laboratory findings revealed a high normal TSH of 4.08 μIU/mL. Initial TPO antibodies and TGA were
both within normal ranges although the participant’s previous bloodwork from less than six months prior to
the study showed elevated TPO antibodies. Her hs-CRP was normal at 0.98 mg/L. Initial organic acid
nutritional testing was markedly abnormal with only vitamin C in the normal range. There were marked
elevations in suberic and adipic acids. She had an elevated methylmalonic suggestive of vitamin B12
deficiency [29]. Glutaric acid was elevated, suggesting a riboflavin deficiency [26]. Xanthurenate was
elevated, suggesting a B6 deficiency [28]. RBC analysis of omega-3 volumes was low, with elevations in
omega-6 RBC volume resulting in a markedly disturbed omega-3:omega-6 ratio. Urinary amino acids
suggested significant protein catabolism given elevations in multiple essential and non-essential amino
acids. Her toxic element screen revealed an elevated whole blood lead at 3.41 mcg/dL. Stool testing revealed
low SCFAs and an overgrowth of Morganella morganii. While fecal calprotectin was normal, there was no
identifiable fecal secretory IgA.
At week six of the program, the participant was counseled to continue with consumption of omega-3 fatty
fish as well as increase animal protein, focusing on red meat as well as organ meats. She was encouraged to
try removing high FODMAP-containing foods, given her gastrointestinal symptoms of bloating and
abdominal pain [25]. She was educated on riboflavin, vitamin B6, and vitamin B12-rich foods, and the use of
AIP-compliant digestive bitters to aid digestion [27].
Following the program, the participant’s MSQ decreased dramatically from 132 to 8,with no frequent or
severe symptoms. The participant reported complete elimination of joint pain and muscle aches, as well as
anxiety, depressed mood, and irritability. Gastrointestinal symptoms completely resolved, she reported the
disappearance of rash/hives, improved energy, decreased hunger, panic attacks, termination of headaches,
and a six-pound weight loss, with minimal to no continued hair loss.
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 20 of 33
A review of her second FFQ documenting the 10-week program revealed strict adherence to the AIP diet
with regular consumption of bone broth, organ meats, coconut, and AIP starches. She reported multiple
daily servings of cruciferous and leafy green vegetables and increased intake of animal protein.
Laboratory testing revealed that her TSH had decreased from 4.08 to 2.15 μIU/mL, with an increase in free
T4 from 1.19 to 1.47 ng/dL and a decrease in hs-CRP from 0.98 to 0.9 mg/L. TGA and TPO antibodies
remained within the lab reference range. Review of repeat nutritional testing revealed a marked
improvement in multiple domains with the only continued nutrient deficiency being B12 and riboflavin, as
suggested by elevated methylmalonic acid [29] and glutaric acid [26]. Both methylmalonic acid and glutaric
acid, however, had come down dramatically from severe elevations at pre-intervention to just outside the
reference range at post-intervention. Previously elevated whole blood lead fell to within normal limits at
0.31 mcg/dL. Urinary amino acids had normalized, suggesting a resolution of the previously suspected
catabolic physiology. Suberic and adipic acids were now in the normal range. There was a mild elevation in
ketone bodies likely related to the participant’s dietary pattern and weight loss. RBC omega-3 volume
remained low and imbalanced compared to omega-6 fatty acid volume.
Repeat stool testing revealed the resolution of previous M. morganii overgrowth with continued
insufficiency of beneficial organisms and low SCFAs. There was an isolated elevated fecal phospholipid
without other evidence of lipid malabsorption. Fecal calprotectin remained normal and fecal secretory IgA
increased to within normal limits.
Case 12
Case 12 involved a32-year-oldfemale with a past medical history of iron deficiency and eczema who began
the program on 125 mcg of levothyroxine. She wanted to decrease stress, improve fatigue and eczema, and
address bloating and IBS-like symptoms. She entered the program with a moderately elevated symptom
burden (MSQ = 83), with the worst symptoms affecting the HEENT, dermatological, gastrointestinal,
genitourinary, musculoskeletal, and neuropsychological systems. Her complaints specifically consisted of
headaches, dizziness, dark circles under her eyes, acne, dry skin, hair loss, belching, bloating, joint pain,
stiffness, muscle aches, fatigue, tiredness, apathy, poor memory, indecisiveness, anxiety, mood swings,
irritability, and depressed mood, as well as frequent/urgent urination. Her initial FFQ revealed a diet low in
total animal products, numerous fruits and vegetables, occasional dairy, regular corn, and refined and whole
gluten-containing grain products. Her supplements consisted of collagen and iron.
Initial laboratory findings revealed a TSH of 0.73μIU/mL,TPO antibodies at 438 IU/mL, a TGA of 3.2
IU/mL,and a hs-CRP of 0.29 mg/L. Initial organic acid testing revealed elevated adipic and suberic acids and
increased needs for riboflavin [26], vitamin B6 [28], folate [23], and vitamin B12 [29]. RBC analysis of omega-
3s was within normal limits and related to the participant’s regular consumption of fatty fish. Urinary amino
acids were elevated and suggested catabolic physiology given the participant’s vigorous, regular resistance
and cardiometabolic exercise without sufficient rest. Her toxic element screen revealed elevated whole blood
mercury at 4.50 mcg/L and lipid peroxides were also elevated, with low serum CoQ10.
Stool testing revealed low SCFAs and pancreatic insufficiency as measured by low fecal elastase [30]. There
was also microscopic evidence of Blastocystis hominis, normal fecal calprotectin, and undetectable fecal
secretory IgA.
At week six of the program, the participant was counseled to continue the consumption of animal protein,
including red meat and organ meats as well as other foods high in thiamine, riboflavin, B6, folate, and
B12.Additionally, she was encouraged to explore the inclusion of fermented foods and AIP-compliant bitters
to support digestion [27].
Following theprogram,the participant’s MSQ decreased from 83 to 25, with symptoms of mood swings and
her depressed mood improved. On the exit questionnaire, the participant reported complete resolution of
eczema and joint complaints, improved energy, and satisfaction with the elimination of grains, including
gluten-containing products as well as corn. The participant reported increased resilience amidst continued
life stressors. She did not report changes in weight.
A review of her second FFQ documenting the10-weekprogram revealed strict adherence to the AIP diet, with
significantly increased and regular consumption of unprocessed animal protein, coconut, and AIP starches.
Laboratory testing revealed suppression of her TSH to 0.23 μIU/mL. Her hs-CRP remained low at 0.32 mg/L
and both TGA and TPO antibodies remained unchanged at 4.8 IU/mL and 452 IU/mL, respectively.Given the
stability in the participant’s weight, but decreasing TSH to now suppressed levels, the authors speculated
that the improvements in thyroid function were directly related to elements of the dietary and lifestyle
intervention positively impacting thyroid hormone production and absorption of the participant’s
replacement medication.
Review of repeat nutritional testing revealed normalization of suberic and adipic acids, FIGLU, and glutaric
acid as well as xanthurenate. The participant persisted with borderline elevated methylmalonic acid,
normalization of urinary amino acids, suggesting a reversal of previous catabolic physiology, and
normalization of lipid peroxides. Previously elevated whole blood mercury fell into the normal range from
4.74 to 3.45 mcg/L.
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 21 of 33
Repeat stool testing revealed a continuation of low fecal elastase, as well as continued microscopic evidence
of B. hominis. There was, however, a normalization of fecal secretory IgA, and fecal calprotectin remained
within normal limits.
At the conclusion of the study, the participant decreased her thyroid replacement medication to 100 mcg of
levothyroxine while seeking evaluation and support for pancreatic insufficiency.
Case 13
Case 13 involved a44-year-oldfemale who began the program on 125 mcg of Tirosint and 15 mcg of
Liothyronine. She sought to reduce stress, improve fatigue and eczema, and address bloating and IBS-like
symptoms. She entered the program with a moderately severe symptom burden (MSQ = 77) with the worst
symptoms affecting the HEENT, dermatological, gastrointestinal, musculoskeletal, and neuropsychological
systems. Specifically, her complaints consisted of headaches, dark circles under her eyes, dry skin, hair loss,
diarrhea, constipation, belching, bloating, joint pain, arthritis, stiffness, muscle aches, fatigue, tiredness,
apathy, poor memory, poor concentration, anxiety, mood swings, and irritability. Her initial FFQ revealed a
diet high in animal products, including beef and pork, low intake of eggs and fatty fish, no gluten-based
grains or dairy consumption, infrequent gluten-free grains, and numerous fruits and vegetables. Her
supplements consisted of a probiotic, “adrenal adaptogens,” magnesium, glutamine, vitamin D, vitamin K2,
dehydroepiandrosterone (DHEA), 5-HTP, and liposomal glutathione.
Initial laboratory findings revealed a TSH of 0.65μIU/mL, TPO antibodies of 30 IU/mL, elevated TGA at
826.8 IU/mL, and a hs-CRP of 1.95 mg/L. Initial organic acid nutritional testing revealed mildly elevated
suberic acid. There was suspicion for a folate deficiency, as suggested by elevated FIGLU [23]. Lipid peroxides
were also elevated. Stool testing revealed no lipid malabsorption or pathogenic overgrowth. There were low
normal SCFAs and a normal fecal calprotectin.
At week six of the program, the participant was counseled to continue consumption of fatty fish and organ
meats. She was provided with guidance on folate-rich foods and to consider the inclusion of fermented
foods.
Following theprogram,the participant’s MSQ decreased from 77 to 25, with notable improvements in joint
pain, cognition, and mood. On the exit questionnaire, the participant reported continued challenges with
stress without markedly noticeable changes in her overall health. The participant reported a desire to
continue prioritizing stress management practices.
A review of her second FFQ documenting the10-weekprogram showed strict adherence to the AIP diet, with
increased intake of certain fruits and vegetables and the use of AIP-compliant starches. Repeat laboratory
testing revealed an elevated TSH of 5.07 μIU/mL while free and total hormones remained within the normal
range. On questioning, the participant was surprised by the increased TSH, given some mild improvements
in symptoms and no symptoms of worsening hypothyroidism. She reported that she had large fluctuations
with her TSH in the past, with difficulty titrating medication and maintaining a stable TSH. Her hs-CRP
decreased from 1.95 to 1.63 mg/L, TPO antibodies remained unchanged at 29 IU/mL and TGA rose slightly to
884.3 IU/mL.
Repeat nutritional testing revealed normalized adipic acid but slightly elevated suberic acid. FIGLU
remained elevated, however, lipid peroxides normalized.Repeat stool testing revealed no changes outside of
a notable overgrowth of K. pneumonie. Given the previous concerns for arthritis and the noticeable presence
of K. pneumonie, the participant was counseled on testing for HLA-B27.
Case14
Case 14involved a33-year-oldfemale, with no additional significant past medical history, who began the
study taking120mg ofNP thyroid.She sought toimprove energy, decrease inflammation, and lose weight.
Initial MSQ was 55, with the worst symptoms affecting the HEENT, dermatological, gastrointestinal,
andneuropsychological systems. Complaints consisted of pruritic ears, watery/pruritic eyes, stuffy nose,
sinus problems, hay fever, excessive mucus, hyperhidrosis, mild hair loss, diarrhea, constipation, bloating,
fatigue, tiredness, infrequent poor concentration, comprehension and memory, and anxiety. Her initial FFQ
revealed a diet consisting of a variety of fruits, vegetables, regular unprocessed and occasional processed
meats, infrequent dairy with regular use of non-dairy creamer, both refined and whole grain products,rice,
daily coffee, and weekly alcohol use.She endorsed taking between 5,000 to 10,000 IU vitamin D daily as well
as 100 mcg of vitamin K2.
Initial laboratory findings revealedborderline low TSH at 0.42 μIU/mL and free and total T4 and T3 in the
low normal range. Her hs-CRP wasslightly elevated at 1.71mg/L, TPO antibodies were slightly elevated at 99
IU/mL with TGA <0.9 IU/mL.Vitamin D was noted to be high normal at 81.8 ng/mL and serum calcium just
outside the normal range at 10.3 mg/dL. Given the concern for hypercalcemia and hypervitaminosis D, the
participant was asked to discontinue the use of vitamin D until reassessment at the end of the 10-week
study.
Initial organic acid nutritional testing revealed an elevation in adipic acid. The participant had significantly
elevated ketone bodies despite not following a low carbohydrate diet, which was concerning for possible
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 22 of 33
cellular insulin resistance.Stool testingrevealed very lowSCFAsandan overgrowth of Klebsiellaoxytoca,
Pseudomonas aeruginosa, and Enterobacter cloacae. There was evidence of significant lipid malabsorption,
as evidenced by elevated fecal phospholipids and fecal cholesterol. Fecal secretory IgA and calprotectin were
within normal limits.
At week six of the program, the participant was counseled to continue consuming animal protein, including
organ meats.She was encouraged to explore the inclusion of fermented foodsand the use of AIP-compliant
digestive bitters to support digestion [27]
Following theprogram,the participant’s MSQ decreased from 56to12withimprovements insleep, sustained
energy, and reduction in HEENT symptoms, bloating, and only occasional loose stools. She reported a 12-
pound weight loss and a desire to continue with stress management practices to support her health.
A review of her second FFQ documenting the10-weekprogram revealed strict adherence to the AIP diet, with
the elimination of refined carbohydrates, potatoes, eggs, legumes, nuts, seeds, grains, and dairy, as well as
the increased consumption of unprocessed meat, vegetables, and fruit and the new, regular inclusion ofbone
broth, sweet potatoes, fermented foods, and coconut-based products.
Repeat laboratory testing revealeda significantly suppressed TSH at 0.069 μIU/mL, a free T3 increase from
2.3 to 2.9 ng/dL, a decrease of TPO antibodies from 99 to 75 IUI/mL, TGA <0.9 IU/mL, a decrease in hs-CRP
from 1.71 to 0.70 mg/L, and a normalization of vitamin D at 50.8 ng/mL.
Repeat stool testingrevealed improved, but continued, concern for lipid malabsorption and low SCFAs. There
was no growth of any of the previously identified potentially pathogenic organisms. On the exit interview,
the participant was instructed to seek digestive enzyme supplement therapy and further work-up for
continued lipid malabsorption.
Case 15
Case 15involved a43-year-oldfemale, with no additional significant past medical history, who began the
study taking150 mg of Armour.She expressed a desire to improve her diet, improve sleep,lose weight,
improve energy and cognition, and begin a structured exercise protocol.She entered the program with a
severesymptom burden (MSQ = 103) with the worst symptoms affecting the HEENT, dermatological,
gastrointestinal, genitourinary, musculoskeletal,and neuropsychologicalsystems. More specifically, she
complained of headaches, dizziness, dark circles under her eyes, pruritic ears and otalgia, acne, dry skin,
rashes, hair loss, flushing, constipation,belching,bloating, abdominal pain,joint pain, stiffness, muscle
aches, fatigue, tiredness, lethargy, poor concentration,poor coordination, indecisiveness, anxiety, mood
swings, irritability, frequent urination, and insomnia. She additionally complained of excessive weight gain,
food cravings, and water retention.
Her initial FFQ revealed a diet consisting of a variety of fruits, vegetables, regular unprocessed and
processedmeats, eggs, infrequent seafood, regular dairy consumption, potatoes, limited refined or whole
grains or grain-based products,daily coffee, and weekly alcohol. The participant was not taking any
supplements or additional medications.
Initial laboratory findings revealed a markedly suppressed TSH of0.026μIU/mL, with total and free hormone
levels within normal ranges.TPO antibodies were noted at 141IU/mL, TGA at 21.8IU/mL,and hs-CRP was
elevated at 1.85 mg/L. The participant was asked given the significantly suppressed TSH, to lower her
medication dose to 120 mg.
Initial organic acid nutritional testing revealed borderline elevated methylmalonic acid, suggesting
borderline vitamin B12 deficiency [29], as well as elevated suberic and adipic acids. Her toxic element screen
revealed a slightly elevated whole blood tin at 0.45 mcg/L. Stool testing showed normal SCFAs,
butanovergrowth of C. freundii and E. cloacae.
At week six of the program, the participant was counseled to continue with increased consumption of
omega-3 fatty fish and animal protein, including organ meats, and explore theinclusion of fermented foods
as tolerated.
Following theprogram,the participant’s MSQ significantly decreased from103to36withthe only continued
symptom of hair loss.She reported a 10-poundweight loss, increasedenergy, improved sleep, decreased food
cravings, improved resilience, decreased bloating, and improved cognitive functioning.
A review of her second FFQ documenting the10-weekprogram revealed strict adherence to the AIP diet with
the elimination of refined carbohydrates, potatoes, eggs, legumes, nuts, seeds, grains, and dairy, as well as
increases in the consumption of unprocessed meat, vegetables, fruit, andregular inclusion of coconut
products and AIP-approved starches. The participant did report some accidental consumption of gluten in
beverages and processed products in the first few weeks of the program with noticeable negative effects on
energy and stools that improved after the discovery and elimination of the gluten-containing products.
Repeat laboratory testing revealed TSH of 0.244μIU/mL,withfree and total hormone levels staying within
normal limits, hs-CRP decreased to 0.94 mg/L,TPO antibodies decreased from 141 to 111 IU/mL, and TGA
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 23 of 33
remained clinically unchanged.
Repeat nutritional testing revealedcontinued slight elevation in adipic acid. Methylmalonic acid remained
elevated, suggesting B12 deficiency [29], however, previously elevated whole blood tin had normalized. The
participant also now had slightly elevated ketones likely related to weight loss and lower carbohydrate diet.
Repeat stool testing revealed no evidence of lipid malabsorption and no overgrowth of previously identified
potentially pathogenic organisms, however, there was a reduction in the predominant SCFA butyrate [23].
Upon the completion of the study, the participant decreased her medication from 120 mg Armour to 90 mg.
Given the persistently elevated methylmalonic acid in the setting of normal and even increased animal
protein intake, the participant was instructed by the study doctor to seek further diagnostic evaluation for
potential autoimmune gastritis compromising B12 absorption.
Case 16
Case16involved a26-year-oldfemale, with no additional significant past medical history, who began the
study without the use of thyroid replacement medication. She reported the use of the dietary supplement
Standard Process Thyrotrophin PMG, which is a bovine protomorphogen devoid of active thyroxine.She
sought to improve her dietary patterns, improve energy, cognition, resilience, and become more educated
about dietary and lifestyle choices that could support her health. She entered the program with a
severesymptom burden (MSQ = 106) with the worst symptoms affecting the HEENT, dermatological, cardiac,
respiratory, gastrointestinal, genitourinary, musculoskeletal,neuropsychological and immunesystems. More
specifically, her complaints consisted of headaches, blurred/tunnel vision, excessive mucus, canker sores,
acne, dry skin, rashes,hair loss, flushing, palpitations,shortness of breath/difficulty taking a deep breath,
constipation,bloating, abdominal pain,joint pain, stiffness, muscle aches, fatigue, tiredness,lethargy, poor
memory and concentration, poor coordination, indecisiveness, anxiety, mood swings, depressed mood,
frequent urination and frequent illness. She additionally complained of food cravings and compulsive
eating.
Her initial FFQ revealed a largely vegetarian-based diet with infrequent chicken and egg consumption, a
large variety of fruits,numerous whole grains, pea protein, coffee and tea with no alcohol consumption.
Outside of the previously mentioned dietary supplement, she was taking zinc, selenium, vitamin D, vitamin
K2 and cod liver oil.
Initial laboratory findings revealed a TSH of1.49μIU/mL with total and free hormone levels within normal
ranges.She was noted with initial TPO antibodies of 120IU/mL, TGA of <0.09 IU/mL, a hs-CRP of 1.06 mg/L,
and a low WBC count of 3.3 x 103 / μL.
Initial organic acid nutritional testing revealed no concerning vitamin or mineral deficiencies. Toxic element
screen revealed no concerning findings. RBC analysis for RBC PUFA volume showed high normal omega-3
volume with a normal omega-3: omega-6 ratio.
Stool testing no bacterial overgrowth with slightly low SCFAs. There was no evidence of lipid malabsorption.
At week six of the program, the participant was counseled to continue the consumption of omega-3 fatty
fish and increase animal protein consumption, including organ meats, and well as fermented foods.
Following theprogram,the participant’s MSQ significantly decreased from106to23 with the only continued
significant symptoms of hair loss (improved), headaches (improved), and hyperhidrosis.She reported
significantly increasedenergy, improved sleep, fewer food cravings, improved resilience, resolved joint pain,
decreased depression, less frequent and severe migraines, no significant gastrointestinal symptoms, and
marked improvements in dry skin/ acne, and improved cognitive functioning.She reported significantly
improved functioning in her job as a healthcare provider.
A review of her second FFQ documenting the10-weekprogram revealed strict adherence to the AIP diet with
the elimination of refined carbohydrates, potatoes, eggs, legumes, nuts, seeds, grains, and dairy, as well as
increases in the consumption of vegetables and fruit,andthe new regular inclusion of chicken, kombucha,
fermented foods, coconut products, such as coconut yogurt, and AIP starches such as cassava.
Repeat laboratory testing revealed a post-intervention TSH of 3.48μIU/mL,with very slight increases infree
and total hormone levels. hs-CRP decreased from 1.06 to 0.16 mg/L. TPO antibodies decreased from 120 to
105 IU/mL, and TGA remained clinically unchanged <0.9 IU/mL. Interestingly, the patient’s previously low
WBC count of 3.3 x 103/μL increased at post-intervention to 4.0 x 103/μL. Her monocyte
percentage decreased from an elevated 14% to within normal limits at 9% and her lymphocytes increased
from 36% pre-intervention to 42% post-intervention.
Repeat nutritional testing revealedoverall balanced vitamin and minimal markers with the exception of a
now elevated FIGLU, suggesting folate deficiency [23]. She remained with ideal RBC volume of omega-3 fatty
acids as well as no concerning levels of whole blood heavy metals. Repeat stool testing revealed no
identifiable potentially pathogenic organisms as well as low normal SCFAs. There were still no signs of lipid
malabsorption.
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 24 of 33
Upon completion of the study, the participant remained without the use of thyroid hormone replacement
medication.
Case 17
Case 17involved a27-year-oldfemale, with a significant past medical history within the past year of a severe
varicella zoster infection, slight elevation in anti-CCP antibodies, without clinical evidence of rheumatoid
arthritis, and a diagnosis of HT three months prior to study onset, who began the study on a small dose of
Armour (15 mg).She sought to improve her dietary patterns, improve energy, cognition, resilience, and
become more educated about dietary and lifestyle choices that could support her health. She hoped to
alleviate the most troubling symptoms of fatigue, moodiness, hair loss, and dry skin and reverse HT such
that she would no longer need replacement medication.
She entered the program with a moderate symptom burden (MSQ = 75), with the worst symptoms affecting
the HEENT, skin, gastrointestinal, genitourinary,neuropsychological, and immuneparameters. More
specifically, her complaints consisted of watery or itchy eyes and swollen red eyelids, stuffy nose, excessive
mucus, stuffy nose, sinus problems, canker sores, acne, dry skin, rashes,hair loss, flushing,
constipation,bloating, abdominal pain, fatigue, tiredness,lethargy, poor memory and concentration,
indecisiveness, anxiety, mood swings, irritability, frequent urination, and frequent illness.
Her initial FFQ revealed a diet transitioning from a vegetarian template to now regular chicken, egg, and fish
consumption, non-dairy creamer with no regular dairy consumption, a large variety of fruits, unrefined
whole grains, infrequent rice, numerous nuts and seeds, coconut, decaf coffee, occasional tea, with no
alcohol consumption. She had discontinued supplementation prior to the study but reported previous use of
a B complex, vitamin D, iron, collagen, oregano, quercetin, and magnesium.
Initial laboratory findings revealed a TSH of1.77μIU/mL, with total and free hormone levels within normal
ranges.Her additional initial labs included TPO antibodies of 138IU/mL, TGA of 66.6 IU/mL, hs-CRP of 0.88
mg/L, and a borderline low WBC count of 3.5 x 103/μL and 10% monocytes.
Initial organic acid nutritional testing revealed no concerning vitamin deficiencies. Zinc levels were
borderline low and significantly lower than plasma copper, resulting in a depressed copper to zinc ratio.
Toxic element screen revealed no concerning findings with only a high normal whole blood mercury at 2.64
mcg/L. RBC analysis for RBC PUFA volume showed high normal omega-3 volume with a normal omega-3/6
ratio.
Stool testing revealed numerous imbalances, including mild lipid malabsorption, low butyrate, and an
overgrowth of Citrobacter freundii and Morganella morganii.
At week six of the program, the participant was counseled to continue the consumption of omega-3 fatty
fish, animal protein, including organ meats, as well as the inclusion of fermented foods. She was provided
with education to explore the exclusion of high FODMAP-containing foods, given her symptoms of
constipation and bloating [25]. She was additionally supported with information regarding the use of AIP-
compliant digestive bitters to support improve the digestion and absorption of nutrients [27].
Following theprogram,the participant’s MSQ significantly decreased from75to25, with the only continued
severe symptoms of hair loss (which had become less frequent and overall improved).She reported
significantly increasedenergy, improved sleep, improved resilience, improved sinus and allergic symptoms,
more stable mood, less severe and frequent gastrointestinal symptoms, and improved cognitive
functioning.She reported significantly improved functioning in her job as a healthcare provider.
A review of her second FFQ documenting the10-weekprogram revealed strict adherence to the AIP diet, with
the elimination of refined carbohydrates, potatoes, eggs, legumes, nuts, seeds, grains, and dairy, as well as
increases in the consumption of unprocessed meat, vegetables, and fruit,andthe new, regular inclusion of
more animal protein, fermented foods, and AIP starches.
Repeat laboratory testing revealed a post-intervention TSH of 2.2μIU/mL,with continued stability infree and
total hormone levels. hs-CRP decreased from 0.88 to 0.80 mg/L. TPO antibodies increased slightly from 138
to 155 IU/mL with TGA also slightly increasing from 66.6 to 76.9 IU/mL. Interestingly, the patient’s
previously borderline low WBC count of 3.5 x 103/μL had only increased slightly to a post-intervention level
of 3.6 x 103/μL. Her monocyte percentages remained at 10%.
Repeat nutritional testing revealedbalanced vitamin and mineral markers improved minimal markers, with
the exception of a now slightly elevated FIGLU, suggesting folate deficiency [23]. She remained with an ideal
RBC volume of omega-3 fatty acids as well as no concerning levels of whole blood heavy metals.
Interestingly her plasma copper had decreased from high normal ranges and was now in a nearly 1:1 ratio
with plasma zinc.
Repeat stool testing revealed a marked improvement and increase in butyrate. She continued with an
overgrowth of C. freundii but now had no evidence of M. morganii. Previously noted mild lipid
malabsorption had resolved.
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 25 of 33
Upon completion of the study, the participant remained using only 15 mg of Armour but was going to seek
changing medications to 25 mcg of Tirosint, removing the T3 component, with future considerations for
titrating off medication entirely.
Raw data tables
Table 7 includes the baseline laboratory data for the 17 participants completing blood chemistry testing pre-
intervention.
Lab
AIP 001
(*,** )
AIP 002
(***)
AIP 003
(**)
AIP
004
AIP 005
(#)
AIP
006
AIP
007
AIP
008
AIP
009
AIP
010
AIP
011
AIP
012
AIP 013
(****)
AIP
014
AIP 015
(**)
AIP
016
AIP
017
TSH (μIU/mL)
0.424 (*,**
)
4.75 3.55 (**) 2.85 1.48 1.64 1.06 13.45 2.79 2.09 4.08 0.736 0.653 0.42
0.026
(**)
1.49 1.77
total T4 (μg/dL) 12.3 (*,** ) 6.5 2 (**) 8.3 7.6 8.1 6.5 6.1 4.7 6.5 7.8 7.4 7.6 5.5 6.8 ( **) 6.4 8.2
total T3 (ng/dL) 149 (*,** ) 106 131 (**) 101 118 82 80 137 84 90 95 98 142 78 138 (**) 97 115
free T4 (ng/dL) 2.9 (*,** ) 2.6 0.31 (**) 1.4 1.29 1.48 1.11 1.02 0.82 1.02 1.19 1.41 1.31 1.05 1.07 (**) 1.07 1.26
free T3 (pg/mL) 1.36 (*,** ) 0.91 3.3 (**) 2.7 3.3 2.2 2.2 3.1 2.2 2.3 2.6 3 3.4 2.3 3.4 (**) 2.6 2.8
reverse t3 (ng/dL) 28.2 (*) 17.1 <5.0 (**) 24.7 14.7 27.3 15.9 12.9 15.7 13.4 15.9 15.4 16.1 16.5 15.9 (**) 13.2 17.1
TPO (IU/mL) 477 (*) 374 135 180 365 135 273 185 471 >600 16 438 30 99 141 120 138
TGA (IU/mL) 5.7 (*) 0 2 603.5 200.7 0 4.7 1.8 3.4 2.1 0 3.2 826.8 0 21.8 0 66.6
WBC (x103 / μL) 8.3 (*) 7.9 5.8 4.8 4.5 6.9 4.8 9 6 6.8 7.3 4.6 6.4 (****) 4.9 4.8 3.3 3.5
Neutrophils (%) 50 (*) 63 59 57 40 69 57 70 55 58 68 58 49 58 63 47 49
Lymphocytes (%) 39 (*) 28 30 33 50 21 28 21 33 37 21 30 34 32 29 36 39
Monocytes (%) 9 (*) 8 7 6 8 8 8 6 8 5 9 9 12 7 7 14 1 0
Eosinophils (%) 2 (*) 1 4 3 2 1 6 2 3 0 2 2 4 3 1 2 1
Basophils (%) 0 (*) 0 0 1 0 1 1 1 1 0 0 1 1 0 0 1 1
Absolute Neutrophils
(x103 / μL)
4.2 (*) 5 3.4 2.8 1.8 4.8 2.8 6.3 3.4 3.9 4.9 2.6 3.2 2.8 3 1.5 1.7
Absolute Lymphocytes
(x103 / μL)
3.2 (*) 2.2 1.7 1.6 2.2 1.4 1.3 1.9 2 2.5 1.6 1.4 2.2 1.6 1.4 1.2 1.4
Absolute Monocytes (x103
/ μL)
0.7 (*) 0.6 0.4 0.3 0.4 0.5 0.4 0.5 0.5 0.4 0.6 0.4 0.8 0.3 0.3 0.5 0.4
Absolute Eosinophils
(x103 / μL)
0.1 (*) 0.1 0.2 0.1 0.1 0.1 0.3 0.1 0.2 0 0.2 0.1 0.2 0.1 0 0.1 0
Absolute Basophils (x103 /
μL)
0 0 0 0 0 0.1 0 0.1 0 0 0 0 0.1 0 0 0 0
hs-CRP (mg/L) 14.07 (*) 6.97 (***) 0.23 2.64 0.65 0.72 0.43 2.59 0.67 2.42 0.98 0.29 1.95 1.71 1.85 1 .06 0.88
TABLE 7: Pre-intervention laboratory data including thyroid parameters, thyroid antibodies, WBC,
and differential cell count. Note: TGA <0.9 IU/mL was reported as 0 in the table and treated as 0 in
the statistical analysis. TPO antibodies >600 IU/mL were treated as 600 IU/mL in the statistical
analysis.
AIP (autoimmune protocol), TSH (thyroid stim ulating hormone), TPO (thyroid peroxidase antibodies), TGA (anti-thyroglobulin antibodies), WBC (white
blood cell), hs-CRP (high sensitivity C-reac tive protein), (*) acutely sick, (**) decreased or changed thyroid medication during the stud y because of the pre-
intervention result or because of irregular me dication dosing, (***) hs-CRP outlier, (****) WBC count outlier, (#) did not complete post-intervention testing
Table 8 includes baseline HRQL for the 17 participants completing the SF-36 pre-intervention.
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 26 of 33
SF 36 Score AIP
001
AIP
002
AIP
003
AIP
004
AIP
005
AIP
006
AIP
007
AIP
008
AIP
009
AIP
010
AIP
011
AIP
012
AIP
013
AIP
014
AIP
015
AIP
016
AIP
017
SF 36 Physical
Functioning 65 80 95 75 100 95 85 80 55 90 85 90 60 95 75 55 15
SF 36 Physical Role
Functioning 0 50 100 25 100 0 25 25 0 50 25 100 0 100 100 0 0
SF 36 Emotional Role
Functioning 0 33.3 33.3 100 33.3 0 0 33.3 0 33.3 100 100 100 10 0 66.7 33.3 0
SF 36 Vitality 10 20 25 30 75 40 25 30 5 20 15 25 0 50 10 10 25
SF-36 Mental Health 56 68 44 72 76 52 36 36 60 40 48 40 60 68 72 44 60
SF 36 Social Role
Functioning 62.5 62.5 62.5 62.5 75 50 62.5 50 37.5 25 37.5 100 50 87.5 87.5 50 75
SF 36 Bodily Pain 67.5 45 67.5 67.5 90 67.5 47.5 67.5 32.5 32.5 35 80 67.5 77.5 47.5 55 90
SF 36 General Health 20 35 40 45 75 80 40 35 10 10 30 60 25 65 55 40 40
TABLE 8: Pre-intervention SF-36 subcale scores
SF-36 (36-Item Short Form Health Survey); AIP (autoimmune protocol)
Table 9 includes the baseline clinical symptom burden for the 17 participants completing the MSQ pre-
intervention.
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 27 of 33
MSQ AIP
001
AIP
002
AIP
003
AIP
004
AIP
005
AIP
006
AIP
007
AIP
008
AIP
009
AIP
010
AIP
011
AIP
012
AIP
013
AIP
014
AIP
015
AIP
016
AIP
017
MSQ Head Score 9 4 2 4 2 7 5 7 4 9 10 8 2 1 6 5 1
MSQ Eye Score 6 3 4 0 3 0 10 3 8 1 9 4 5 3 3 4 5
MSQ Ear Score 3 2 0 0 0 0 2 2 9 5 7 0 1 4 7 0 0
MSQ Nose Score 16 5 13 0 1 0 13 2 16 3 9 0 1 7 0 2 13
MSQ Mouth/Throat
Score 3 5 1 0 0 0 6 1 0 9 5 0 1 1 3 1 4
MSQ Skin Score 9 12 7 7 3 0 11 8 6 9 12 8 7 5 11 1 2 8
MSQ Heart Score 0 1 0 0 1 2 1 2 3 1 4 1 2 0 0 6 0
MSQ Lung Score 1 1 0 0 0 0 1 1 0 0 4 0 1 0 0 4 0
MSQ Digestive
Score 14 3 10 9 6 6 12 11 9 14 9 7 5 11 11 10 8
MSQ Joint/Muslce
Score 11 13 4 12 1 13 5 15 16 8 18 20 15 3 15 12 5
MSQ Weight Score 16 20 15 7 15 0 10 16 1 10 8 4 3 1 0 12 10 1
MSQ
Energy/Activity
Score
12 7 8 4 3 6 12 9 6 10 10 10 1 1 2 7 9 9
MSQ Mind Score 12 4 12 5 0 13 14 16 28 2 9 4 12 4 12 14 5
MSQ Emotion
Score 11 11 4 3 2 9 8 12 7 8 13 13 10 4 11 11 6
MSQ Other Score 3 7 3 4 0 0 4 3 6 0 5 4 1 0 5 6 10
MSQ Total Score 12 6 98 83 55 37 5 6 114 108 119 89 132 83 77 55 103 106 75
TABLE 9: Pre-intervention MSQ scores (subscales and total)
MSQ (Medical Symptoms Questionnaire), AIP (autoimmune protocol)
Table 10 includes the post-intervention laboratory data for the 16 participants completing blood chemistry
testing following the 10-week dietary and lifestyle intervention. Note: Participant AIP 005 did not complete
the study and, as such, there is no data presented in the table below.
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 28 of 33
Lab
AIP 001
(*,**)
AIP 002
(***)
AIP 003
(**)
AIP
004
AIP 005
(#)
AIP
006
AIP
007
AIP 008
(*)
AIP
009
AIP
010
AIP
011
AIP
012
AIP 013
(****)
AIP
014
AIP 015
(**)
AIP
016
AIP
017
TSH (μIU/mL) 0.92 (*,**) 2.32 7.35 (**) 2.06 1.55 1.13
31.92
(*)
3.06 0.535 2.15 0.23 5.07 0.069
0.244
(**)
3.48 2.2
total T4 (μg/dL) 13.1 (*,**) 6.1 5 (**) 9.8 8.3 6.6 8.3 (*) 5.2 6.9 8.8 8 7.1 5.4 6.4 (**) 6.6 6.4
total T3 (ng/dL) 98 (*,**) 93 107 (**) 84 78 84 154 (*) 83 79 78 99 92 101 88 (**) 96 101
free T4 (ng/dL) 1.8 (*,**) 2.3 0.77 (**) 1.59 1.49 1.19 1.1 (*) 0.86 1.23 1.47 1.53 1.14 1.07 0.91 (**) 1.11 1.21
free T3 (pg/mL) 1.61 (*,**) 0.91 2.5 (**) 2.6 2.2 2.5 3. 1(*) 2.3 2.4 2.4 2.8 2.4 2.9 2.2 (**) 2.8 2.8
reverse t3 (ng/dL) 54.7 (*,**) 15.9 10.9 (**) 30.5 27.7 17.9 17.5 (*) 13 14.8 23.3 20.6 18 16.3 20.3 (**) 13.6 17.2
TPO (IU/mL) 598 (*) 409 107 177 160 190 123 (*) 481 >600 14 452 29 75 111 105 155
TGA (IU/mL) 3.1 (*) 0 0.9 735.7 0 4.8 4.5 (*) 3.6 1.7 0 4.8 884.3 0 20.7 0 76.9
WBC (x103 / μL) 6.1(*) 6.6 4.4 3.8 5.9 3.9 11.1 (*) 5.5 4.6 6.7 4.5 8.3 (****) 4.2 5.6 4 3.6
Neutrophils (%) 58 (*) 66 57 51 59 55 76 (*) 44 48 71 57 52 61 66 44 51
Lymphocytes (%) 32 (*) 28 31 38 32 34 17 (*) 44 46 19 32 37 29 27 42 37
Monocytes (%) 10 (*) 5 8 7 7 6 5 (*) 7 6 8 9 7 7 7 9 10
Eosinophils (%) 0 (*) 1 4 3 1 4 1 (*) 4 0 2 2 2 3 0 3 1
Basophils (%) 0 (*) 0 0 1 1 1 1 (*) 1 0 0 0 1 0 0 2 1
Absolute Neutrophils
(x103 / μL)
3.5 (*) 4.3 2.5 2 3.5 2.1 8.4 (*) 2.4 2.2 4.7 2.5 4.4 2.6 3.6 1.8 1.8
Absolute Lymphocytes
(x103 / μL)
1.9 (*) 1.9 1.4 1.5 1.9 1.3 1.9 (*) 2.4 2.1 1.2 1.4 3.1 1.2 1.5 1.7 1.3
Absolute Monocytes (x103
/ μL)
0.6 (*) 0.3 0.4 0.3 0.4 0.2 0.6 (*) 0.4 0.3 0.6 0.4 0.6 0.3 0.4 0.4 0.4
Absolute Eosinophils
(x103 / μL)
0 (*) 0.1 0.2 0.1 0 0.2 0.1 (*) 0.2 0 0.1 0.1 0.2 0.1 0 0.1 0
Absolute Basophils (x103 /
μL)
0 (*) 0 0 0 0 0 0.1 (*) 0 0 0 0 0.1 0 0 0.1 0
hs-CRP (mg/L) 11.7 (*) 5.02 (***) 0.42 2.9 0.76 0.38 6.52 (*) 0.36 0.84 0.9 0.32 1.63 0.7 0.94 0.1 6 0.8
TABLE 10: Post-intervention laboratory data, including thyroid parameters, thyroid antibodies,
WBC, and differential cell count. Note TGA <0.9 IU/mL was reported as 0 in the table and treated
as 0 in the statistical analysis. TPO antibodies >600 IU/mL were treated as 600 IU/mL in the
statistical analysis.
AIP (autoimmune protocol), TSH (thyroid stim ulating hormone), TPO (thyroid peroxidase antibodies), TGA (anti-thyroglobulin antibodies), WBC (white
blood cell), hs-CRP (high sensitivity C-reac tive protein), (*) acutely sick, (**) decreased or changed thyroid medication during the stud y because of the pre-
intervention result or because of irregular me dication dosing, (***) hs-CRP outlier, (****) WBC count outlier, (#) did not complete post-intervention testing
Table 11 includes post-intervention HRQL for the 16 participants completing the SF-36 survey following the
10-week dietary intervention. Note: Participant AIP 005 did not complete the study and, as such, there is no
data presented in the table below.
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 29 of 33
SF 36 Score AIP
001
AIP
002
AIP
003
AIP
004
AIP
005 (#)
AIP
006
AIP
007
AIP
008
AIP
009
AIP
010
AIP
011
AIP
012
AIP
013
AIP
014
AIP
015
AIP
016
AIP
017
SF 36 Physical
Functioning 70 95 100 90 95 95 95 95 100 95 100 75 95 80 100 100
SF 36 Physical Role
Functioning 100 100 100 100 75 50 25 50 100 100 100 25 100 100 50 100
SF 36 Emotional Role
Functioning 33.3 100 100 100 66.7 100 0 100 100 100 100 100 100 0 100 0
SF 36 Vitality 30 70 40 65 70 45 35 35 85 70 75 15 80 55 55 60
SF-36 Mental Health 72 88 76 88 80 60 52 84 100 84 68 68 92 76 64 80
SF 36 Social Role
Functioning 87.5 87.5 50 75 100 75 50 75 100 100 87.5 75 100 75 87.5 75
SF 36 Bodily Pain 77.5 77.5 100 90 35 90 7 5 7 7.5 100 90 90 67.5 100 67.5 77.5 67.5
SF 36 General Health 50 65 85 55 95 60 35 40 90 7 5 8 5 5 0 85 70 80 70
TABLE 11: Post-intervention SF-36 subscale scores
AIP (autoimmune protocol), SF-36 (36 Item S hort Form Health Survey), # (did not comple te post-intervention testing)
Table 12 includes the post-intervention clinical symptom burden for the 16 participants completing the
MSQ following the 10-week dietary intervention. Note: Participant AIP 005 did not complete the study and,
as such, there is no data presented in the table below.
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 30 of 33
MSQ AIP
001
AIP
002
AIP
003
AIP
004
AIP
005 (#)
AIP
006
AIP
007
AIP
008
AIP
009
AIP
010
AIP
011
AIP
012
AIP
013
AIP
014
AIP
015
AIP
016
AIP
017
MSQ Head Score 6 0 1 2 2 6 9 1 0 0 0 0 0 1 2 0
MSQ Eye Score 2 3 2 0 1 7 6 3 0 0 0 3 0 3 2 2
MSQ Ear Score 0 0 0 0 0 0 0 0 1 0 0 1 1 0 0 0
MSQ Nose Score 11 1 0 0 0 7 1 1 0 0 0 0 1 1 0 5
MSQ
Mouth/Throat
Score
2000 021010000 2 10
MSQ Skin Score 4 0 1 5 0 5 9 5 3 1 2 3 1 4 7 3
MSQ Heart Score 1 0 0 1 2 0 4 0 0 0 0 0 0 0 2 0
MSQ Lung Score 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0
MSQ Digestive
Score 4113 99116023425 3 4
MSQ Joint/Muslce
Score 1304 419202451 4 0 4
MSQ Weight
Score 3224 449101313 4 4 1
MSQ
Energy/Activity
Score
4002 038201421 2 01
MSQ Mind Score 1 1 2 2 6 7 8 5 1 0 1 3 1 8 1 0
MSQ Emotion
Score 3003 447401831 2 1 3
MSQ Other Score 1 1 1 1 1 1 3 2 0 0 0 0 0 0 0 2
MSQ Total Score 43 12 10 28 33 56 85 32 6 8 25 25 12 36 23 25
TABLE 12: MSQ subscale and total scores post-intervention
AIP (autoimmune protocol), MSQ (Medical S ymptoms Questionnaire), (#) did not compl ete post-intervention testing
Table 13 depicts the originally calculated p-values, ordered from lowest to highest matched
with corresponding corrected p-values for statistical significance following the use of a false discovery rate
correction, given the study's multiple hypotheses. The corrected p-values of significance for n = 27 tests
were calculated assuming a false discovery rate d = 0.05 using the formula pi = d * (i/n), where n is the
number of tests, i is an integer between 1-27, and pi is the corrected p-value for the given ordered integer.
After performing the correction and matching the ordered and previously calculated p values with its
respective pi, the only original p-value affected corresponded to a change in the mean lymphocyte count
from pre- to post-intervention. Given this correction, the study authors could not reliably state that there
was a significant difference between the mean lymphocyte count from pre- to post-intervention. No other p-
values were affected by the false discovery rate correction.
2019 Abbott et al. Cureus 11(4): e4556. DOI 10.7759/cureus.4556 31 of 33
P1 P2 P3 P4 P5 P6 P7 P8 P9 P10 P11 P12 P13 P14 P15 P16 P17 P18 P 19 P20 P21 P22 P23 P24 P25
i 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
Pi
value
0.0019 0.0037 0.0056 0.0074 0.0093 0.0111 0.0130 0.0148 0.0167 0.0185 0.0204 0.0222 0.0241 0.0259 0.0278* 0.0296 0.0315 0.0333 0.0352 0.0370 0.0389 0.0407 0.0426 0.0444 0.0463
Original
p-value
0.0001 0.0001 0.0001 0.0001 0.0001 0.0010 0.0020 0.0020 0.0057 0.0063 0.0110 0.0110 0.0112 0.0219 0.0286* 0.0684 0.0743 0.1240 0.1396 0.176 0.183 0.385 0.418 0.455 0.565
TABLE 13: False discovery rate corrections for p-values
i (integer: 1-27), Pi value (corrected p-value), * (correction to not statistically significant)
Additional Information
Disclosures
Human subjects: Consent was obtained by all participants in this study. Valley Health/Winchester Medical
Center IRB issued approval 20160401. The Institutional Review Board of the Valley Health/Winchester
Medical Center approved theconduction of this study # 20160401 via an expedited review on June 4, 2018.
TheValley Health/Winchester Medical CenterIRB is organized and operated by Policies and Procedures as set
forth in the Federal Register. This is to certify that the following Institutional Review Board/Ethics
Committee is in compliance with Good Clinical Practice Guidelines as defined by the U.S. Food and Drug
Administration under the Code of Federal Regulations (21 CFR Parts 50 and 56; 45 CFR Part 46) and
International Conference onHarmonisation(ICH) Guidelines (Section E6). IRB00006173, expiration date
August 5, 2018, and FWA00015109, expiration date July 7, 2022. Animal subjects: All authors have
confirmed that this study did not involve animal subjects or tissue. Conf licts of interest: In compliance
with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: The
study authors received $11,428.60 as part of a community crowdfunding campaign throughIndieGoGoto pay
for the operating expenses of the study. Genova Diagnostics provided testing supplies that included 40
comprehensive stool analysis (GI Effects™ and 40nutritionalorganic acid tests (NutrEval™) as part of the
study. Financial relationships: Robert Abbott M.D. declare(s) personal fees from Autoimmune Wellness
LLC. Dr. Robert Abbott is medical advisor for the health and wellness initiative Autoimmune Wellness LLC.
He receives financial compensation to the amount of $2000 yearly for his participation in writing scientific
and medical articles for this entity. He has received no direct compensation including grants or financial
support in relation to the completion of this work. . Other relationships: Angie Alt is co-founder of the
health and wellness platform Autoimmune Wellness LLC that seeks to educate and empower individuals to
make lifestyle changes in support of living with and healing from autoimmune disease. She has a group
online health coaching program SAD to AIP in SIX that was used as the primary intervention for this study.
Acknowledgements
We would like to acknowledge and thank numerous members of the greater citizen scientist community for
their generous donations that made performing this research possible. We would like to thank Dr. Lihong
Chen M.D, Ph.D. of Genova Diagnostics Laboratory for donating urinary and plasma organic acid tests as
well as comprehensive stool analyses for use in the study. We would like to thank Mickey Trescott for her
valuable support in organizing the study's crowdfunding campaign and overall support of the study team.
We would like to thank Andrea Hirsh, NTP, for her time as a health coach and nutritional therapy
practitioner during the study. We would lastly like to thank Kerri Cooper R.D. for her services as a registered
dietician supervising study participants during the multi-week dietary intervention.
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Hashimoto’s thyroiditis (HT) is the most common autoimmune disease and the leading cause of hypothyroidism, in which damage to the thyroid gland occurs due to the infiltration of lymphocytes. It is characterized by increased levels of antibodies against thyroid peroxidase and thyroglobulin. In this review, we present the metabolic profile, the effectiveness of micronutrient supplementation and the impact of dietary management in patients with HT. For this current literature review, the databases PubMed, Cochrane, Medline and Embase were reviewed from the last ten years until March 2022. This article provides a comprehensive overview of recent randomized controlled trials, meta-analyses, and clinical trials. Many patients with HT, even in the euthyroid state, have excess body weight, metabolic disorders, and reduced quality of life. Due to frequent concomitant nutritional deficiencies, the role of vitamin D, iodine, selenium, magnesium, iron and vitamin B12 is currently debated. Several studies have underlined the benefits of vitamin D and selenium supplementation. There is still no specific diet recommended for patients with HT, but a protective effect of an anti-inflammatory diet rich in vitamins and minerals and low in animal foods has been suggested. There is insufficient evidence to support a gluten-free diet for all HT patients. Pharmacotherapy, along with appropriate nutrition and supplementation, are important elements of medical care for patients with HT. The abovementioned factors may decrease autoantibody levels, improve thyroid function, slow down the inflammatory process, maintain proper body weight, relieve symptoms, and prevent nutritional deficiencies and the development of metabolic disorders in patients with HT.
... The diet should be rich in antioxidants, i.e., vitamins A, C, E, polyphenols, and omega-3 fatty acids. At the same time, supplementing the diet with minerals such as selenium, io-dine, magnesium, zinc, and copper is more important for Hashimoto's patients than eliminating gluten itself [55]. A statistically significant reduction in TSH after 12 months was found in a recent clinical study where 62 patients with Hashimoto's disease were considered (including 32 on a gluten-free diet), but no such relationship was observed after 3 and 6 months of dieting. ...
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The popularization of the gluten-free diet brings with it a fashion for its use, which can harm the treatment of Hashimoto’s disease. The few studies in this regard do not confirm positive changes resulting from a gluten-free diet. At the same time, the presence of other comorbid autoimmune diseases in this group of patients is increasing. This may have important implications for the interpretation of test results and the need for a gluten-free diet in some patients. In this review, the PubMed database was searched for links between a gluten-free diet, Hashimoto’s disease, and autoimmune diseases. When analyzing the available literature, we found no basis for introducing a gluten-free diet for the standard management of Hashimoto patients. The recommended diet is instead an anti-inflammatory diet that levels the supply (to compensate for deficiencies) of vitamin D, iodine, and selenium, which are found in plant products rich in polyphenols, antioxidants, and omega-3 fatty acids, as illustrated in this article.
... Echter heb ik in de maand mei van 2021 nog geen informatie kunnen vinden of ze ook ooit in een interventioneel onderzoek zijn getest. Een niet zo veganistische adaptatie van het paleolithische dieet is ook geprobeerd bij de patiënten van Hashimoto, maar leek de schildklierfunctie niet te verbeteren [15]) welke suppletie met zwarte komijnpoeder niet alleen leidde tot een gezonde significante vermindering van het lichaamsgewicht, maar ook tot een statistisch significante verlaging van het schildklierstimulerend hormoon, hetgeen een verbetering van de schildklierfunctie betekent, en het verlaagde zelfs het niveau van auto-immuun anti-thyroïde antilichamen, evenals een toename van bloedspiegels van schildklierhormoon T3, en er was een significante daling in de pro-inflammatoire celsignaleringsverbinding heterodimeer cytokine-eiwitcomplex interleukine 23, waarvan wordt aangenomen dat het verlagende effect van deze verbindingen de autoimmuun ontsteking van de schildklier bevordert, hetgeen een ontstekingsremmende eigenschap van de plant laat zien, en bovendien werd er een daling van 17 [%] procent van het relatief "slechte" LDL-cholesterol waargenomen [7,8,9]. Gezien het feit dat patiënten met Hashimoto een bijzonder hoog risico lopen op het ontwikkelen van hartaandoeningen, zou dit ook kunnen helpen bij de behandeling van Hashimoto-gerelateerde metabole afwijkingen [10]. ...
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Author: Rody Mens-r.w.mens@student.tue.nl Citation: Mens RW. 13 February 2022. Nigella sativa continual meta-analysis; www.nutritionfactsnederlands.nl/videoscript/2022/2/15/alfalfa-medicago-sativa-continual-meta-analysis ; https://www.researchgate.net/publication/358615213_Alfalfa_medicago_sativa_continual_meta-_analysis Some keywords: Summary: The Nigella sativa seeds may help as nutrition for the cardiovascular system, as nutrition for the reproductive system, as nutrition for the immune system and as nutrition for the thyroid. Article: Nigella sativa [Sources below] The peppery flavored black cumin seed nigella sativa (also known as NS, n. sativa, black cumin, nigella sativa, miracle herb and black seed) is categorizable as a member of the buttercup (and thus not the carrot family of cumin meaning that the black cumin seed nigella sativa is not really to be considered as cumin [1]) is relatively easily usable by example putting it in a pepper mill grinding it onto foods just like you could with black pepper and is possibly usable for: > It may be usable as nutrition for the cardiovascular system since systematic reviews and meta-analyses of randomized controlled trials have found that daily black cumin consumption significantly improves cholesterol, triglycerides, blood pressure, and blood sugar control [2, 3]. one study found that postmenopausal women randomized to 1 (one) gram (which is less than about a quarter teaspoon) a day of black cumin powder reduced their LDL cholesterol by 27 [%] (percent) within 2 (two) months which was significantly better than the placebo which are the kind of results in the effect range of what you would expect from a certain (such as cholesterol, e.g. LDL cholesterol) cardiovascular lipid-lowering "statin" "drug", yet this was just a sprinkle of a vegetative cooking spice [4] of which the daily dose used in most of these studies would cost a few dollar or (exclusive or) euro cents a day. >It may even help as nutrition for the reproductive system with menopausal symptoms since in a study result showed that in perimenopausal women it lowered LDL-cholesterol levels and a month after stopping the use of the spice the cholesterol levels started to creep back up so that it does appear to be a cheap, safe, effective (and delicious if you like things spicy) treatment for
... But the effectiveness of the current treatments such as glucocorticoids, levothyroxine and specific diet for the management of HT has been questioned in recent years. [4][5][6][7] Vitamin D is a steroid molecule whose primary function is to control bone metabolism and calcium and phosphorus homeostasis. ...
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Introduction Recent evidence suggested that vitamin D deficiency was associated with Hashimoto's thyroiditis (HT) pathogenesis and thyroid hypofunction. This study aimed to investigate whether vitamin D supplementation would be effective in the prevention and progression of hypothyroidism in patients with HT. Methods PubMed, Embase and the Cochrane library were searched for randomized controlled trials (RCTs) and prospective cohort studies published from inception to August 2021. Results A total of 7 cohorts of patients from six clinical trials with 258 patients with HT were included. Significant difference was found (WMD = 19.00, 95% CI: 12.43, 25.58, p < 0.001; I2 = 90.0%, pheterogeneity < 0.001) between the vitamin D group and control group in serum 25-hydroxyvitamin D level. And the combined results indicated vitamin D supplementation significantly reduced the level of thyroid peroxidase antibodies (TPO-Ab) compared to the control group (WMD = −158.18, 95% CI: −301.92, −14.45, p = 0.031; I2 = 68.8%, pheterogeneity = 0.007). Whereas no significant differences were found on the levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4) compared to the control group (p > 0.05). What is New and Conclusion Our study demonstrated that vitamin D treatment might significantly increase the serum 25(OH)D levels and produce changes in TPO-Ab titres. No significant association was found between serum vitamin D treatment and the levels of TG-Ab, TSH, FT3 and FT4, suggesting that vitamin D is not associated with the function of the thyroid in patients with HT.
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Introduction Data suggest dietary modification can improve clinical responses in inflammatory bowel disease (IBD). The goal of this study was to determine the efficacy of an autoimmune protocol diet in patients with Crohn's disease and ulcerative colitis. Methods We enrolled adults with active IBD (Harvey–Bradshaw index ≥ 5 or partial Mayo score ≥3 and erosions on endoscopy and/or elevated fecal calprotectin). For the autoimmune protocol, patients underwent 6-week elimination followed by 5-week maintenance phase. Clinical indices, laboratories, and biomarkers were assessed at baseline and weeks 6 and 11. Endoscopy was performed at study completion. Results The final cohort included 15 patients with IBD, with mean disease duration 19 years (SD 14.6) and active biological use in 7 (47%) patients. Nutrient repletion was initiated for deficiencies in vitamin D (n = 3) and iron (n = 6). From week 0 to weeks 6 and 11, mean partial Mayo score significantly improved from 5.8 (SD 1.2) to 1.2 (SD 2.0) and 1.0 (SD 2.0) for ulcerative colitis, and mean Harvey–Bradshaw index significantly improved from 7 (SD 1.5) to 3.6 (SD 2.1) and 3.4 (SD 2.6) for Crohn's disease. C-reactive protein did not significantly change during study. Mean fecal calprotectin improved from 471 (SD 562) to 112 (SD 104) at week 11 (P = 0.12). Among those with follow-up endoscopy at week 11 (n = 7), improvements were noted in simple endoscopic score for Crohn's disease (n = 1), Rutgeerts score (n = 1), and Mayo endoscopy subscore (n = 4). Discussion Dietary elimination can improve symptoms and endoscopic inflammation in patients with IBD. Randomized controlled trials are warranted.
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Hashimoto's thyroiditis (HT) is a chronic autoimmune thyroid disease caused by an interaction between genetic factors and environmental conditions, both of which are yet to be fully understood. The management of HT depends on its clinical manifestations, commonly including diffuse or nodular goiter with euthyroidism, subclinical hypothyroidism and permanent hypothyroidism. However, in most cases of patients with HT, lifelong levothyroxine substitution is required. The additional role of diet for the management of HT is usually overlooked. A literature search regarding the importance and the influence of iodine, selenium, vitamin D and gluten on HT was conducted. In HT careful supplementation of possible deficiencies is recommended for the dietary management of these patients. The use of a diet low in gluten among HT patients with or without celiac disease (CD) is discussed.
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