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GAPS Nutritional Protocol - How Healing the Gut Removes the Basis for All Chronic Diseases

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A growing amount of research highlights the relationship between damaged gut microbiome and chronic illnesses - mental and physical. Healing the gut is becoming a priority in treating any chronic disease. The GAPS Nutritional Protocol has been designed for this purpose and has been used all over the world for twenty years. It has yielded successful results and is very distinct from other dietary interventions. Not only it focuses on healing the gut wall and repopulating the gut flora with beneficial microbes, but also provides the body with fundamental building blocks to heal and restore its ana- tomical structure. Through this article, we aim to remind our readers of the importance of gut health in a large array of dis- orders, describe the GAPS Nutritional Protocol, and encourage research on dietary interventions such as this one.
© 2021 International Society for Orthomolecular Medicine ISSN 0317-0209
OPEN ACCESS
VOLUME 36, NUMBER 3
PUBLISHED 06 SEPTEMBER 2021
ABSTRACT
A growing amount of research highlights the relationship
between damaged gut microbiome and chronic illnesses -
mental and physical. Healing the gut is becoming a priority
in treating any chronic disease. The GAPS Nutritional Protocol
has been designed for this purpose and has been used all over
the world for twenty years. It has yielded successful results
and is very distinct from other dietary interventions. Not only
it focuses on healing the gut wall and repopulating the gut
ora with benecial microbes, but also provides the body
with fundamental building blocks to heal and restore its ana-
tomical structure. Through this article, we aim to remind our
readers of the importance of gut health in a large array of dis-
orders, describe the GAPS Nutritional Protocol, and encourage
research on dietary interventions such as this one.
GUT MICROBIOME
The human body is populated by a myriad of microbes; it
is an ecosystem. Nothing in the body is microbe-free, and
all sorts of microbes are present in our inner microbial
community: fungi, bacteria, viruses, protozoa, archaea, etc
(Faintuch & Faintuch, 2019; Hallen-Adams & Suhr, 2017;
Lurie-Weinberger & Gophna, 2015).
So far, the research has largely focussed on bacteria, esti-
mating that our bodies contain as many bacterial cells as
human cells, with 90% of them in our gut (Sender, Fuchs, &
Milo, 2016). This part of our microbial community is called
the gut ora or gut microbiome, and it plays a fundamen-
tal role in human health and disease (Hao & Lee, 2004) The
gut with its microbial community is often referred to as our
second brain, but its structure and connections are so com-
plex that some researchers name it the rst brain (Petra et
al., 2015; Quigley, 2017).
Our digestive system with its microbiome is responsible for
proper digestion and absorption of food, neutralisation of
toxic substances, and production of vitamins, hormones,
and neurotransmitters (Cénit et al., 2014; Clarke et al., 2014;
Yoshii, Hosomi, Sawane, & Kunisawa, 2019). It is the head-
quarters of our immune system, ensuring its health, vitality,
proper balance, and functions (Belkaid & Hand, 2014; Wu
& Wu, 2012). All of these have far-reaching consequences
for human health. In short, the gut holds the roots of our
health. No matter how far removed from the gut an organ
or tissue may be, its health and function are determined,
to a large degree, by the state of the gut and its microbial
community (Salem, Ramser, Isham, & Ghannoum, 2018).
In any microbial community, if there is balance between
various species of microbes, then there is harmony and
health. When this balance is damaged by antibiotics, chem-
icals in food and drink, and other inuences, the gut ora
becomes imbalanced – this is called gut dysbiosis.
In gut dysbiosis, pathogenic microbes impair food diges-
tion and absorption, leading to multiple nutritional
deciencies. They damage the integrity of the gut wall,
making it porous and leaky (Fasano, 2011, 2012; Sapone
et al., 2006; Sturgeon & Fasano, 2016). Undigested food
absorbs through this damaged gut wall, triggering food
allergies and intolerances (Camilleri, 2019). Pathogenic
microbes in the gut produce toxic substances (Din & Alam,
2020; Kaji et al., 1976; Zioudrou, Streaty, & Klee, 1979),
which absorb through the damaged gut wall, causing
EDUCATIONAL ARTICLE
GAPS Nutritional Protocol: How Healing the Gut Removes
the Basis for All Chronic Diseases
OPEN ACCESS
Sophie Delaunay-Vagliasindi; Stephanie Sene; Natasha Campbell-McBride
Citation: Delaunay-Vagliasindi S, Sene S & Campbell-McBride N (2021) GAPS Nutritional Protocol: How healing the gut removes the
basis for all chronic diseases. J Orthomol Med. 36(3)
GAPS Nutritional Protocol: How Healing the Gut Removes the Basis for All Chronic Diseases
2 | Journal of Orthomolecular Medicine, Volume 36, Number 3, 2021
THE GAPS NUTRITIONAL PROTOCOL
AND THE GAPS DIET
GAPS stands for Gut And Psychology Syndrome and Gut
And Physiology Syndrome. Its core principles rely on the
need for a healthy microbiome for our body to function
correctly. The most important part of the protocol is the
GAPS Diet (Campbell-McBride, 2020).
The GAPS Diet is based on traditional diets from all over
the world and focusses on foods with high-density, easi-
ly-digestible nutrition. It eliminates all dicult-to-digest
and damaging substances. All foods are cooked at home
from fresh natural ingredients. Re-building connective tis-
sues of the patient is a particular focus. Fermented foods
are used extensively. Full implementation of the GAPS Diet,
over time, eliminates the need for nutritional supplements,
as the food provides all the necessary building materials
for healing and maintenance of the human body.
The GAPS Diet has several variations (Campbell-McBride,
2020, pp 162-281), but the two main ones are The Full GAPS
Diet and The GAPS Introduction Diet. The Full GAPS Diet is
followed as a permanent lifestyle, and it is easier to imple-
ment. The GAPS Introduction Diet is designed for deeper
healing: it is a stage-by-stage introduction of nourishing
foods, starting from the easiest-to-digest to more di-
cult-to-digest foods (see Campbell-McBride, 2020). It can
be followed at the beginning of the protocol or at any point
when deeper healing is required. The more damaged is the
gut of the person, the more it is necessary to go through
the GAPS Introduction Diet. This diet is particularly eec-
tive in removing abnormal intestinal permeability (leaky
gut). Once enough healing in the gut is achieved through
The GAPS Introduction Diet, the person moves on to The
Full GAPS Diet to continue healing the whole body.
The GAPS Diet removes all toxic and processed substances:
processed foods, food additives, antibiotics, toxic metals,
butter substitutes and vegetable oils, sugar, grains, starch,
soy and industrial meat and dairy. When following the
GAPS Diet one should source the cleanest natural foods,
to avoid agricultural chemicals. Especially concerning
is glyphosate, widely used herbicide which disrupts the
gut microbiome, chelates minerals, damages organs and
tissues, and impairs liver detoxication (Samsel & Sene,
2013; Sene, 2021).
Nutrient-dense animal foods (meat, sh and eggs) and
meat/sh stocks are central to the GAPS Diet. The human
body is largely made out of connective tissue, the gut
wall in particular. Connective tissues of animals and birds,
disease (Borba, Lerner, Matthias, & Shoenfeld, 2020; Din
& Alam, 2020; Sanctuary, Kain, Angkustsiri, & German, 2018;
Sokolov et al., 2014; Woodford, 2021). In short, in a person
with abnormal gut ora the digestive system becomes a
major source of toxicity, instead of being a source of nutri-
tion. The immune system reacts to the whole situation,
launching systemic inammation and autoimmunity. Our
gut produces and regulates many hormones, neurotrans-
mitters, and other powerful molecules, all of which get out
of balance in gut dysbiosis, adding an avalanche of physi-
cal and mental symptoms to the whole picture.
Many health practitioners realise that it is impossible to
treat such a complex situation without changing the per-
son’s diet. Gut dysbiosis is increasingly being found in
cognitive, mental, and autoimmune diseases (Belkaid &
Hand, 2014; Capuco et al., 2020; Cénit, Matzaraki, Tigchelaar,
& Zhernakova, 2014; Dinan & Cryan, 2017; Foster & McVey
Neufeld, 2013; HeintzBuschart et al., 2018; Jaglin et al.,
2018; Kaplan, Crawford, Field, & Simpson, 2007; Maniscalco
& Rinaman, 2018; Perricone & Shoenfeld , 2019; Rogers et
al., 2016; Sanctuary et al., 2018; Sokolov et al., 2014; Stevens
et al., 2018; Woodford, 2021).
These ndings have led to a concept called gut-brain axis
(Clapp et al., 2017; Cryan et al., 2019). Research on the gut-
brain axis is rapidly growing, and so are the studies looking
at dietary interventions to treat these disorders (Lange et
al., 2017, Rucklidge & Harrison, 2010; Schnorr & Bachner,
2016; Tillisch et al., 2013).
The GAPS Nutritional Protocol with its central piece – The
GAPS Diet – is a global phenomenon, gaining international
popularity over two decades. It has been scarcely studied
(Babinska et al., 2020; Cekici & Sanlier, 2019; Nazarenkov et
al., 2018), and the research has largely focussed on autism
(Abele, Tzivian, Meija, & Folkmanis, 2019; Çikili, Deniz, &
Çakal, 2019). Yet, this protocol is used by people all over the
world to heal from a very long list of mental and physical
diseases, including autoimmune, neurological problems,
hormonal problems, chronic fatigue syndrome, bromyal-
gia, allergies, asthma, eczema, psoriasis and the full list of
learning disabilities and psychiatric maladies.
The purpose of the GAPS Nutritional Protocol is to re-bal-
ance the gut ora and the rest of the microbiome, heal
and seal the ‘leaky’ gut wall, normalise digestion and
absorption of food, re-balance the immune and endocrine
systems, and provide quality building materials for healing
and repair of all the tissues and organs in the human body
(Campbell-McBride, 2010, 2020).
GAPS Nutritional Protocol: How Healing the Gut Removes the Basis for All Chronic Diseases
3 | Journal of Orthomolecular Medicine, Volume 36, Number 3, 2021
Raw organic dairy from natural breads of animals is used
in the GAPS Diet. Patients ferment raw milk and cream at
home for 24 hours, which makes dairy lactose-free and
breaks down casein (Campbell-McBride, 2020). Homemade
yogurt, sour cream, ker, whey and cheese provide probi-
otic microbes, enzymes and high-quality nutrition. Only
raw (unpasteurised) milk and cream from natural breeds of
animals are used (Campbell-McBride, 2020) for maximum
healing eect. Pasteurisation damages the structure of
milk, making it harmful to health and allergenic (Campbell-
McBride, 2020, pp 146-150). Raw milk contains a larger
amount of psychotropic and mesophilic bacterial popu-
lations, healthier than those found in pasteurised milk. In
addition, the bacteria contained in pasteurised milk have
reached a nonculturable form (Quigley et al., 2013a,b).
Consumption of fermented raw milk has yielded positive
results on mood and health issues (Baars, Berge, Garssen,
& Verster, 2019) and has been suggested as ‘preventive
strategies to reduce the incidence of allergic disease’ (van
Neerven, Knol, Heck & Savelkoul, 2012, p. 857). Finally, raw
milk and homemade fermented dairy products have been
found to hold salutogenic eects in immune diseases such
as celiac disease (Lerner & Matthias, 2018). For patients
with milk allergy, home-fermented dairy products are
introduced later in the protocol following specic gradual
steps (Campbell-McBride, 2020, pp 179-183).
Apart from fermented dairy, probiotics in the GAPS Diet
come from fermented vegetables and fruits, prepared at
home. Sauerkraut (fermented cabbage) has been found
to contain the recommended range of lactic acid bacteria
per gram (between 106 and 108) to be called a probiotic
superfood (Orgeron, Corbin, & Scott, 2016). Fermentation
of plant matter makes food more digestible, richer in
bio-available nutrients and a good source of probiotics
and enzymes (Campbell-McBride, 2020, pp 229-245).
Nuts and oily seeds (sunower, pumpkin and sesame) are
used in the GAPS Diet for making bread, cakes and des-
serts, and they are prepared by soaking, fermenting, and
sprouting to remove antinutrients. Antinutrients (enzyme
inhibitors, lectins, phytates, oxalates, etc) are substances
in natural foods that can damage the human body, impair
digestion and cause nutritional deciencies (Campbell-
McBride, 2020, pp 128-129). They are almost exclusively
found in plant foods, particularly in their seeds (grains,
beans, pulses, legumes, seeds and nuts). Enzymes inhibi-
tors can impair digestion, protein synthesis, functioning
of hormones and neurotransmitters and other important
functions. Lectins can damage the immune system, the gut
wall, the joints and many other organs. Phytic acid binds to
cooked with water, release building materials for the
connective tissues of the human being, into the stock
(Campbell-McBride, 2020, pp 218-220). Organ meats (liver,
hearts, lungs, kidneys, tripe, brain, etc.) are used exten-
sively in cooking, providing a plethora of nutrients, which
are missing in muscle meats. Homemade meat stocks,
well-cooked connective tissues and organ meats provide
proteins, amino acids, cholesterol, minerals, glucosamines,
collagens, fat soluble vitamins and all other crucial ele-
ments necessary for healing a damaged gut wall and the
rest of the body (Campbell-McBride, 2020, pp 248-252).
Animal fats and cholesterol-rich foods (raw butter, home-
made ghee, lard, tallow, goose and duck fat), seafood,
avocados, cold-pressed olive oil and coconut oil are central
to the GAPS Nutritional Protocol.
Low-fat diets have been long promoted as the solution
to heart disease (Keys, 1953). The research is mounting
to show that this idea is false (Ravnskov, 2002, 2003), and
that fat and cholesterol are essential to the proper func-
tioning of our bodies. Every cell of every organ contains
a signicant amount of cholesterol in its structure (Enig,
2000; Hussain et al., 2019; Nelson, Lehninger, & Cox, 2008;
Roberts, Alberts, Johnson, Walter, & Hunt, 2002). This is
especially the case in cell membranes, where cholesterol
molecules can make up to half of the plasma membrane
and even more when the cells are part of protective barri-
ers (Garrow, James, & Ralph, 2003; Nelson et al., 2008). The
brain consumes 25% of the body’s cholesterol (Dietschy
& Turley, 2001), and cholesterol is involved in cell com-
munication (Enig, 2000; Hussain et al., 2019; Nelson et al.,
2008; Purves, Orians, Heller, & Sadava, 2004; Roberts et
al., 2002), myelin production and composition (Dietschy
& Turley, 2001; Enig, 2000; Hussain et al., 2019; O’Brien &
Sampson, 1965), functions and structures of synapses
(Dietschy & Turley, 2001; Hussain et al., 2019; Huttenlocher
& Dabholkar, 1997), production of steroid hormones (Berg,
Tymoczko, Gatto, & Stryer, 2015; Garrow, James, & Ralph,
2003; Seeley et al., 2008) and functions of the immune sys-
tem (Bhakdi, Tranum-Jensen, Utermann, & Füssle, 1983;
Claxton et al., 1998; Iribarren et al., 1997; Muldoon et al.,
1997). A low-fat and low-cholesterol diet, together with
cholesterol-lowering drugs, can lead to serious health
problems and impact brain functioning (Cham, Koslik, &
Golomb, 2016; Golomb, Stattin, & Mednick, 2000; Golomb,
Kane, & Dimsdale, 2004; Hussain et al., 2019; Tomson-
Johanson et al., 2020). Campbell-McBride (2018, 2020)
states that animal fats and cholesterol are essential-to-life
substances. This is why they are provided in abundance
by the GAPS Diet.
GAPS Nutritional Protocol: How Healing the Gut Removes the Basis for All Chronic Diseases
4 | Journal of Orthomolecular Medicine, Volume 36, Number 3, 2021
that could be construed as a potential conict of interest.
Dr Natasha Campbell-McBride is the creator of the GAPS
concept and the GAPS Nutritional Protocol.
Funding
No nancial support has been received for the work
reported.
Authors’ Contributions
Sophie Delaunay-Vagliasindi wrote a rst version of the
manuscript. Natasha Campbell-McBride and Stephanie
Sene supervised and edited. All authors read and
approved the nal manuscript.
Acknowledgements
This case was written following the CARE guidelines.
Author’s Information
Sophie Delaunay-Vagliasindi holds a MSc degree in
Developmental Psychology from the University of Kent,
UK. She is a certied GAPS Coach. She is specialising in
the impact of gut ora on development and conducting
research for non-prot organisations. Stephanie Sene is
a Senior Research Scientist at MIT in Cambridge, MA. She
holds a B.S. degree from MIT in biology, and a Ph.D. in elec-
trical engineering and computer science also from MIT.
Her recent research interests are on the role of nutritional
deciencies and toxic chemicals in disease, with a focus on
the mineral sulfur and the herbicide glyphosate. Natasha
Campbell-McBride is a medical doctor with two postgrad-
uate degrees: MMedSci (neurology), MMedSci (human
nutrition). She is the creator of the GAPS concept and the
GAPS Nutritional Protocol.
REFERENCES
Abele S, Tzivian L, Meija L & Folkmanis V (2019) Low Carbohydrate Diet
(SCD/GAPS) for Children with Autistic Spectrum Disorder. International
society for nutritional psychiatry research (ISNPR) conference, London,
United Kingdom, 20-22 October 2019.
Akande KE, Doma UD, Agu HO & Adamu HM (2010) Major antinutrients
found in plant protein sources: their eect on nutrition. Pakistan journal
of nutrition, 9(8), 827-832. https://doi.org/10.3923/pjn.2010.827.832.
Baars T, Berge C, Garssen J & Verster J (2019) The impact of raw fermented
milk products on perceived health and mood among Dutch adults. Nutri-
tion & Food Science. https://doi.org/10.1108/NFS-12-2018-0347.
Babinska K, Celusakova H, Belica I, Szapuova Z, Waczulikova I, Nemcs-
icsova D & Ostatnikova D (2020) Gastrointestinal symptoms and feeding
problems and their associations with dietary interventions, food sup-
plement use, and behavioral characteristics in a sample of children
and adolescents with autism spectrum disorders. International Journal
of Environmental Research and Public Health, 17(17), 6372. https://doi.
org/10.3390/ijerph17176372.
Belkaid Y & Hand TW (2014) Role of the microbiota in immunity
and inammation. Cell, 157(1), 121-141. https://doi.org/10.1016/j.
cell.2014.03.011.
vital minerals and makes them unavailable for the body to
use. Oxalates and oxalic acid also bind minerals in the body
and can cause behavioural abnormalities, painful urination
and chronic cystitis. Glucosinolates found in brassica vege-
tables bind iodine and can contribute to thyroid problems.
Polyphenolic compounds, alkaloids, salicylates, saponins,
tannins and avonoids in plants can all cause problems,
particularly when the person is unable to digest them
(Akande, Doma, Agu, & Adamu, 2010; Freed, 1991, 1999;
Pusztai et al., 1993; Sandstead, 1992; Van Damme, Peumans,
Pusztai, & Bardocz, 1998). GAPS people have a damaged
digestive system and cannot handle many antinutrients.
That is why plant foods present the biggest challenge for
this group of patients. The GAPS Diet removes the worst
oenders such as grains (Cordain, 1999) and, in addition,
insists on vegetables and seeds (beans, nuts and other)
being prepared carefully before consumption, to make
them more digestible (Campbell-McBride, 2020).
Apart from the GAPS Diet, the GAPS Nutritional Protocol
involves a few nutritional supplements (mostly used at
the beginning of the protocol and discontinued later) and
lifestyle changes revolving around the reduction of toxic-
ity from the environment (such as chemical compounds
found in cleaning and beauty products). The protocol is
described in detail in Dr Campbell-McBride’s books Gut
And Psychology Syndrome (2010) and Gut And Physiology
Syndrome (2020).
CONCLUSION
All diseases begin in the gut! This statement, attributed
to Hippocrates, is gaining monumental importance in the
modern world. Gut dysbiosis is increasingly being observed
in a growing list of psychiatric and physical problems, illus-
trating an intrinsic relationship between the state of the
gut and the rest of the body. The GAPS Nutritional Protocol
has been specically designed to heal the human body
starting from the root – the digestive system. This protocol
has been used by people all over the world to heal from
mental and physical illnesses for twenty years. Thousands
of glowing testimonies have been published (Campbell-
McBride, 2012) but scientic research is lacking. We highly
encourage health practitioners and researchers, interested
in addressing gut dysbiosis as the cause of mental and
physical illnesses, to use the GAPS Nutritional Protocol in
their practice and/or empirical studies.
DECLARATIONS
Competing Interests
The authors declare that the research was conducted in
the absence of any commercial or nancial relationships
GAPS Nutritional Protocol: How Healing the Gut Removes the Basis for All Chronic Diseases
5 | Journal of Orthomolecular Medicine, Volume 36, Number 3, 2021
Dietschy JM & Turley SD (2001) Cholesterol metabolism in the
brain. Current opinion in lipidology, 12(2), 105–112. https://doi.
org/10.1097/00041433-200104000-00003.
Din ATU & Alam F (2020) Auto-brewery syndrome: a clinical dilemma.
Cureus, 12(10). https://doi.org/10.7759/cureus.10983.
Dinan TG & Cryan JF (2017) Brain–gut–microbiota axis—mood, metabo-
lism and behaviour. Nature reviews Gastroenterology & hepatology, 14(2),
69-70. https://doi.org/10.1038/nrgastro.2016.200.
Enig M (2000) Know your fats. Silver Spring, MD: Bethesda Press.
Faintuch J & Faintuch S (Eds) (2019) Microbiome and Metabolome in Diag-
nosis, Therapy, and Other Strategic Applications. Academic Press.
Fasano A (2011) Zonulin and its regulation of intestinal barrier function:
the biological door to inammation, autoimmunity, and cancer. Physio-
logical reviews. https://doi.org/10.1152/physrev.00003.2008.
Fasano A (2012) Intestinal permeability and its regulation by
zonulin: diagnostic and therapeutic implications. Clinical Gastroenter-
ology and Hepatology, 10(10), 1096-1100. https://doi.org/10.1016/j.
cgh.2012.08.012.
Foster J & McVey Neufeld K (2013) Gut–brain axis: how the microbiome
inuences anxiety and depression. Trends In Neurosciences, 36(5), 305-
312. https://doi.org/10.1016/j.tins.2013.01.005
Freed DL (1991) Lectins in food: Their importance in health and disease.
Journal of Nutritional Medicine, 2(1), 45-64.
Freed DL (1999) Do dietary lectins cause disease?: The evidence is sug-
gestive—and raises interesting possibilities for treatment.
Garrow JS, James WPT & Ralph A (2003) Human nutrition and dietetics.
Churchill Livingstone.
Golomb BA, Stattin H & Mednick S (2000) Low cholesterol and violent
crime. Journal of psychiatric research, 34(4-5), 301-309. https://doi.
org/10.1016/S0022-3956(00)00024-8.
Golomb BA, Kane T & Dimsdale JE (2004) Severe irritability associated
with statin cholesterol-lowering drugs. Qjm, 97(4), 229-235. https://doi.
org/10.1093/qjmed/hch035.
Hallen-Adams HE & Suhr MJ (2017) Fungi in the healthy human gastro-
intestinal tract. Virulence, 8(3), 352-358. https://doi.org/10.1080/215055
94.2016.1247140.
Hao WL & Lee YK (2004) Microora of the gastrointestinal tract. Public
Health Microbiology, 491-502.
HeintzBuschart A, Pandey U, Wicke T, SixelDöring F, Janzen A, SittigWie-
gand E & Wilmes P (2018) The nasal and gut microbiome in Parkinson’s
disease and idiopathic rapid eye movement sleep behavior disorder.
Movement disorders, 33(1), 88-98. https://doi.org/10.1002/mds.27105.
Hussain G, Wang J, Rasul A, Anwar H, Imran A, Qasim M & Sun T (2019)
Role of cholesterol and sphingolipids in brain development and neu-
rological diseases. Lipids in health and disease, 18(1), 1-12. https://doi.
org/10.1186/s12944-019-0965-z.
Huttenlocher PR & Dabholkar AS (1997) Regional dierences in
synaptogenesis in human cerebral cortex. Journal of com-
parative Neurology, 387(2), 167-178. https://doi.org/10.1002/
(SICI)1096-9861(19971020)387:2<167::AID-CNE1>3.0.CO;2-Z.
Iribarren C, Jacobs Jr, DR, Sidney S, Claxton AJ, Gross MD, Sadler M &
Blackburn H (1997) Serum total cholesterol and risk of hospitalization,
and death from respiratory disease. International journal of epidemiology,
26(6), 1191-1202. https://doi.org/10.1093/ije/26.6.1191.
Berg JM, Tymoczko JL & Stryer L (2002) Biochemistry, ; W. H. New York:
Freeman and Company: New York.
Bhakdi S, Tranum-Jensen J, Utermann G & Füssle R (1983) Binding and
partial inactivation of Staphylococcus aureus alpha-toxin by human
plasma low density lipoprotein. Journal of Biological Chemistry, 258(9),
5899-5904.
Borba VV, Lerner A, Matthias T & Shoenfeld Y (2020) Bovine milk proteins
as a trigger for autoimmune diseases: Myth or reality?. International Jour-
nal, 8(1), 10-21. https://doi.org/10.12691/ijcd-8-1-2.
Camilleri M (2019) Leaky gut: mechanisms, measurement and clinical
implications in humans. Gut, 68(8), 1516-1526. http://dx.doi.org/10.1136/
gutjnl-2019-318427.
Campbell-McBride N (2010) Gut and Psychology Syndrome: natural treat-
ment for autism, dyspraxia, ADD, dyslexia, ADHD, depression, schizophrenia.
Medinform Publishing.
Campbell-McBride N (2012) GAPS Stories: Personal accounts of improve-
ment and recovery through the GAPS Nutritional Protocol. Medinform
Publishing.
Campbell-McBride N (2020) Gut and Physiology Syndrome: Natural Treat-
ment for Allergies, Autoimmune Illness, Arthritis, Gut Problems, Fatigue,
Hormonal Problems, Neurological Disease and More. Medinform Publish-
ing.
Capuco A, Urits I, Hasoon J, Chun R, Gerald B & Wang J, et al (2020) Current
Perspectives on Gut Microbiome Dysbiosis and Depression. Advances In
Therapy, 37(4), 1328-1346. doi: 10.1007/s12325-020-01272-7. https://doi.
org/10.1007/s12325-020-01272-7.
Cekici H & Sanlier N (2019) Current nutritional approaches in managing
autism spectrum disorder: A review. Nutritional neuroscience, 22(3), 145-
155. https://doi.org/10.1080/1028415X.2017.1358481.
Cénit MC, Matzaraki V, Tigchelaar EF & Zhernakova A (2014) Rapidly
expanding knowledge on the role of the gut microbiome in health and
disease. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease,
1842(10), 1981-1992. https://doi.org/10.1016/j.bbadis.2014.05.023.
Cham S, Koslik HJ & Golomb BA (2016) Mood, personality, and behav-
ior changes during treatment with statins: a case series. Drug safety-case
reports, 3(1), 1. https://doi.org/10.1007/s40800-015-0024-2.
Çikili Y, Deniz S & Çakal B. Analysis Of The Eect Of GAPS Diet On Individu-
als With Autism Spectrum Disorder. Journal of Ahmet Kelesoglu Education
Faculty, 1(1), 1-11.
Clapp M, Aurora N, Herrera L, Bhatia M, Wilen E & Wakeeld S (2017) Gut
Microbiota’s Eect on Mental Health: The Gut-Brain Axis. Clinics And Prac-
tice, 7(4), 131-136. https://doi.org/10.4081/cp.2017.987.
Clarke G, Stilling RM, Kennedy PJ, Stanton C, Cryan JF & Dinan TG (2014)
Minireview: gut microbiota: the neglected endocrine organ. Molecular
endocrinology, 28(8), 1221-1238. https://doi.org/10.1210/me.2014-1108.
Claxton AJ, Jacobs Jr, DR, Iribarren C, Welles SL, Sidney S & Feingold K
(1998) Association between serum total cholesterol and HIV infec-
tion in a high-risk cohort of young men. Journal of acquired immune
deciency syndromes and human retrovirology: ocial publication of
the International Retrovirology Association, 17(1), 51-57. https://doi.
org/10.1097/00042560-199801010-00008.
Cordain L (1999) Cereal grains: humanitys double-edged sword. World
review of nutrition and dietetics, 84, 19-19.
Cryan JF, O’Riordan K J, Cowan CS, Sandhu KV, Bastiaanssen TF, Boehme
M & Dinan TG (2019) The microbiota-gut-brain axis. Physiological reviews.
https://doi.org/10.1152/physrev.00018.2018.
GAPS Nutritional Protocol: How Healing the Gut Removes the Basis for All Chronic Diseases
6 | Journal of Orthomolecular Medicine, Volume 36, Number 3, 2021
Quigley L, McCarthy R, O’Sullivan O, Beresford TP, Fitzgerald GF, Ross RP &
Cotter PD (2013)a The microbial content of raw and pasteurized cow milk
as determined by molecular approaches. Journal of dairy science, 96(8),
4928-4937. https://doi.org/10.3168/jds.2013-6688.
Quigley L, O’Sullivan O, Stanton C, Beresford TP, Ross RP, Fitzgerald GF
& Cotter PD (2013)b The complex microbiota of raw milk. FEMS microbi-
ology reviews, 37(5), 664-698. https://doi.org/10.1111/1574-6976.12030.
Quigley EM (2017) Microbiota-brain-gut axis and neurodegenerative dis-
eases. Current neurology and neuroscience reports, 17(12), 1-9. https://doi.
org/10.1007/s11910-017-0802-6
Ravnskov U (2002) Is atherosclerosis caused by high cholesterol?. Qjm,
95(6), 397-403 https://doi.org/10.1093/qjmed/95.6.397.
Ravnskov U (2003) Cholesterol Myths. New Trends Publishing, Incorpo-
rated.
Roberts K, Alberts B, Johnson A, Walter P & Hunt T (2002) Molecular biol-
ogy of the cell. New York: Garland Science.
Rogers GB, Keating DJ, Young RL, Wong ML, Licinio J & Wesselingh S
(2016) From gut dysbiosis to altered brain function and mental illness:
mechanisms and pathways. Molecular psychiatry, 21(6), 738-748. https://
doi.org/10.1038/mp.2016.50
Rucklidge J & Harrison R (2010) Successful Treatment of Bipolar Disorder
II and ADHD with a Micronutrient Formula: A Case Study. CNS Spectrums,
15(5), 289-295. https://doi.org/10.1017/S1092852900027516
Salem I, Ramser A, Isham N & Ghannoum MA (2018) The gut microbiome
as a major regulator of the gut-skin axis. Frontiers in microbiology, 9, 1459.
https://doi.org/10.3389/fmicb.2018.01459.
Samsel A & Sene S (2013) Glyphosate, pathways to modern diseases II:
Celiac sprue and gluten intolerance. Interdisciplinary toxicology, 6(4), 159.
https://doi.org/10.2478/intox-2013-0026.
Sanctuary MR, Kain JN, Angkustsiri K & German JB (2018) Dietary Con-
siderations in Autism Spectrum Disorders: The Potential Role of Protein
Digestion and Microbial Putrefaction in the Gut-Brain Axis. Frontiers in
nutrition, 5, 40. https://doi.org/10.3389/fnut.2018.00040.
Sandstead HH (1992) Fiber, phytates, and mineral nutrition. Nutri-
tion reviews, 50(1), 30–31. https://doi.org/10.1111/j.1753-4887.1992.
tb02464.x
Sapone A, De Magistris L, Pietzak M, Clemente MG, Tripathi A, Cucca F &
Fasano A (2006) Zonulin upregulation is associated with increased gut
permeability in subjects with type 1 diabetes and their relatives. Diabe-
tes, 55(5), 1443-1449. https://doi.org/10.2337/db05-1593.
Schnorr SL & Bachner HA (2016) Integrative Therapies in Anxiety Treat-
ment with Special Emphasis on the Gut Microbiome. The Yale journal of
biology and medicine, 89(3), 397–422.
Seeley R, Stephens T & Tate P (2008) Anatomy and physiology. (8th ed.).
New York: McGraw- Hill.
Sender R, Fuchs S & Milo R (2016) Revised estimates for the number of
human and bacteria cells in the body. PLoS biology, 14(8), e1002533.
https://doi.org/10.1371/journal.pbio.1002533.
Sene S (2021) Toxic Legacy: How the Weedkiller Glyphosate Is Destroying
Our Health and the Environment. Chelsea Green Publishing.
Sokolov O, Kost N, Andreeva O, Korneeva E, Meshavkin V, Tarakanova Y,
Dadayan A, Zolotarev Y, Grachev S, Mikheeva I, Varlamov O & Zozulya A
(2014) Autistic children display elevated urine levels of bovine casomor-
phin-7 immunoreactivity. Peptides, 56, 68–71. https://doi.org/10.1016/j.
peptides.2014.03.007
Jaglin M, Rhimi M, Philippe C, Pons N, Bruneau A, Goustard B & Rabot
S (2018) Indole, a signaling molecule produced by the gut microbiota,
negatively impacts emotional behaviors in rats. Frontiers in neuroscience,
12, 216. https://doi.org/10.3389/fnins.2018.00216.
Kaji H, Asanuma Y, Ide H, Saito N, Hisamura M, Murao M & Takahashi K
(1976) The auto-brewery syndrome–the repeated attacks of alcoholic
intoxication due to the overgrowth of Candida (albicans) in the gastroin-
testinal tract. Materia medica polona, 8(4), 429-435.
Kaplan BJ, Crawford SG, Field CJ & Simpson JSA (2007) Vitamins,
minerals, and mood. Psychological bulletin, 133(5), 747. https://doi.
org/10.1037/0033-2909.133.5.747.
Keys A (1953) Atherosclerosis: a problem in newer public health.
Atherosclerosis, 1, 19.
Lange K, Hauser J, Lange K, Makulska-Gertruda E, Nakamura Y & Reiss-
mann, et al (2017) The Role of Nutritional Supplements in the Treatment
of ADHD: What the Evidence Says. Current Psychiatry Reports, 19(2).
https://doi.org/10.1007/s11920-017-0762-1
Lerner A & Matthias T (2018) The Salutogenic Eects of Cow’s Milk and
Dairy Products in Celiac Disease. Journal Of Clinical & Cellular Immunol-
ogy, 09(02). https://doi.org/10.4172/2155-9899.1000549.
Lurie-Weinberger MN & Gophna U (2015) Archaea in and on the human
body: health implications and future directions. PLoS pathogens, 11(6),
e1004833. https://doi.org/10.1371/journal.ppat.1004833.
Maniscalco JW & Rinaman L (2018) Vagal interoceptive modulation of
motivated behavior. Physiology, 33(2), 151-167. https://doi.org/10.1152/
physiol.00036.2017.
Muldoon MF, Marsland A, Flory JD, Rabin BS, Whiteside TL & Manuck B
(1997) Immune system dierences in men with hypo-or hypercholes-
terolemia. Clinical immunology and immunopathology, 84(2), 145-149.
https://doi.org/10.1006/clin.1997.4382.
Nazarenkov N, Beeken L, Seeger K, Ananthakrishnan A, Khalili H, Lewis JD
& Konijeti GG (2018) Nutritional Adequacy of Popular Dened Diets for
Inammatory Bowel Disease: 736. Ocial journal of the American College
of Gastroenterology ACG, 113, S415. https://doi.org/10.1093/ecco-jcc/
jjx180.779.
Nelson DL, Lehninger AL & Cox MM (2008) Lehninger principles of bio-
chemistry. Macmillan.
O’Brien JS & Sampson EL (1965) Lipid composition of the normal human
brain: gray matter, white matter, and myelin. Journal of lipid research, 6(4),
537-544. https://doi.org/10.1016/S0022-2275(20)39619-X.
Orgeron II RP, Corbin A & Scott B (2016) Sauerkraut: A probiotic super-
food. Functional Foods in Health and Disease, 6(8), 536-543. https://doi.
org/10.31989/hd.v6i8.262.
Perricone C & Shoenfeld Y (Eds) (2019) Mosaic of autoimmunity: the novel
factors of autoimmune diseases. Academic Press.
Petra AI, Panagiotidou S, Hatziagelaki E, Stewart JM, Conti P & Theoharides
TC (2015) Gut-microbiota-brain axis and its eect on neuropsychiatric
disorders with suspected immune dysregulation. Clinical therapeutics,
37(5), 984-995. https://doi.org/10.1016/j.clinthera.2015.04.002.
Purves WK, Orians GH, Heller HC & Sadava D (2004) Life, the Science of
Biology, 7th. Sunderland, Mass: Sinauer Associates, 954.
Pusztai A, Ewen SWB, Grant G, Brown DS, Stewart JC, Peumans WJ & Bar-
docz S (1993) Antinutritive eects of wheat-germ agglutinin and other
N-acetylglucosamine-specic lectins. British Journal of Nutrition, 70(1),
313-321
GAPS Nutritional Protocol: How Healing the Gut Removes the Basis for All Chronic Diseases
7 | Journal of Orthomolecular Medicine, Volume 36, Number 3, 2021
van Neerven RJ, Knol EF, Heck JM & Savelkoul HF (2012) Which fac-
tors in raw cow’s milk contribute to protection against allergies?.
Journal of Allergy and Clinical Immunology, 130(4), 853-858. https://doi.
org/10.1016/j.jaci.2012.06.050.
Woodford KB (2021) Casomorphins and Gliadorphins Have Diverse Sys-
temic Eects Spanning Gut, Brain and Internal Organs. International
journal of environmental research and public health, 18(15), 7911. https://
doi.org/10.3390/ijerph18157911.
Wu HJ & Wu E (2012) The role of gut microbiota in immune homeosta-
sis and autoimmunity. Gut microbes, 3(1), 4-14. https://doi.org/10.4161/
gmic.19320.
Yoshii K, Hosomi K, Sawane K & Kunisawa J (2019) Metabolism of dietary
and microbial vitamin B family in the regulation of host immunity. Fron-
tiers in nutrition, 6, 48. https://doi.org/10.3389/fnut.2019.00048.
Zioudrou C, Streaty RA & Klee WA (1979) Opioid peptides derived from
food proteins. The exorphins. Journal of Biological Chemistr y, 254(7),
2446-2449. https://doi.org/10.1016/S0021-9258(17)30243-0.
Stevens BR, Goel R, Seungbum K, Richards EM, Holbert RC, Pepine CJ
& Raizada MK (2018) Increased human intestinal barrier permeability
plasma biomarkers zonulin and FABP2 correlated with plasma LPS and
altered gut microbiome in anxiety or depression. Gut, 67(8), 1555-1557.
http://dx.doi.org/10.1136/gutjnl-2017-314759.
Sturgeon C & Fasano A (2016) Zonulin, a regulator of epithelial and endo-
thelial barrier functions, and its involvement in chronic inammatory
diseases. Tissue barriers, 4(4), e1251384. https://doi.org/10.1080/216883
70.2016.1251384.
Tillisch K, Labus J, Kilpatrick L, Jiang Z, Stains J, Ebrat B & Mayer EA (2013)
Consumption of fermented milk product with probiotic modulates brain
activity. Gastroenterology, 144(7), 1394-1401. https://doi.org/10.1053/j.
gastro.2013.02.043.
Tomson-Johanson K, Kaart T, Kiivet RA, Veidebaum T & Harro J (2020)
Low cholesterol levels in children predict impulsivity in young adult-
hood. Acta neuropsychiatrica, 32(4), 196-205. https://doi.org/10.1017/
neu.2019.48.
Van Damme EJ, Peumans WJ, Pusztai A & Bardocz S (1998) Handbook of
plant lectins: properties and biomedical applications. John Wiley & Sons.
... It is recommended that health practitioners and researchers use the GAPS nutrition protocol in their practices in order to prevent intestinal dysbiosis, which is shown to be the cause of mental and physical diseases. 19 In this research, the main diets that dietitians consider applicable are the elimination diet (85.4%), low FODMAP diet (80.8%), autoimmune protocol diet (72.2%), and GAPS diet (70.7%), and the supplements they find applicable are probiotic-prebiotic (91.4%), multivitamin-mineral (84.8%) and plant-based supplements (75.8%). Although there is an opinion that the low FODMAP diet, which aims 20 to find a balance between symptomatic improvements without potential negative effects on dietary restriction, can become applicable in primary care therapy, the clinical use of this diet is still limited. ...
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... Special attention is given to the neutralization of antinutrients in legumes and other plant foods (Akande, Doma, Agu, & Adamu, 2010). For a detailed description of the GAPS Diet please see Delaunay-Vagliasindi, Seneff, and Campbell-Mcbride (2021) and GAPS books by Dr N Campbell-McBride. ...
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Background A robust evidence base for dietary recommendations for patients with inflammatory bowel disease (IBD) is lacking, and patients are increasingly turning to popular defined diets for management of symptoms and inflammation. However, many proposed diets involve elimination of various foods or food groups, and may exacerbate or inadequately replete micronutrient deficiencies prevalent in many patients with IBD at baseline. The goal of this study was to compare the dietary reference intake (DRI), a collection of reference values assessing nutrient intake from the Institute of Medicine, among various published and/or popular dietary protocols for patients with IBD. Methods Dietary comparisons of USDA General Recommendations (modified according to recommendations from the Crohn’s & Colitis Foundation for IBD; USDA-CCF), autoimmune protocol (AIP) diet, specific carbohydrate diet (SCD), Crohn’s disease exclusion diet (CDED) ± partial enteral nutrition (PEN), IBD-anti-inflammatory diet (IBD-AID), low FODMAP diet, and gut and psychology syndrome (GAPS) diet were performed. Protocol differences regarding elimination, allowance, duration of elimination and maintenance phases, unique features, and published data regarding efficacy were compared. Typical macronutrient and micronutrient intake with such diets were calculated and compared using published sample menus. Results Published data indicate clinical response or remission rates of 40–80% from mostly non-randomised studies (sample size ranging from 9 to 417) across all diets. There are no published data on efficacy of USDA-CCF or GAPS in IBD. Elimination phases range from 2 to 8 weeks, with maintenance phases lasting at least 5 weeks or remaining undefined. For an average 35-year-old man or woman, most diets adequately met macronutrient requirements, except fibre (Table 1). Daily caloric range was 1135–2661 kcal. All diets were sufficient in B12. Iron intake was generally adequate for men (6 of 8 diets), but inadequate for women (1 of 8 diets). Most diets (7 of 8) failed to meet RDI for vitamin D and calcium, while at least 3 of 8 were deficient in omega-3 and zinc. Conclusions Limited data are available to guide clinicians on use of dietary protocols for IBD. These results indicate potential for nutritional inadequacy of popular defined diets for IBD. Partnership with registered dietitians are needed to guide patients with IBD in nutrition and dietary intervention. Larger randomised studies are needed to support evidence-based dietary recommendations for IBD.