Neuro-Nutrition as Support for Physiological Function and Cognitive Abilities in Individuals With Down Syndrome, Autism Spectrum Disorder, and Attention-Deficit/Hyperactivity Disorder
Phase: NA
Conditions: Down Syndrome, Autism Spectrum Disorder, Attention Deficit Hyperactivity Disorder (ADHD)
Sponsor: Elizabeth Guadalupe Ibarra Coronado

GENERAL PROJECT DATA 
Research Line: Health. Nutrition. Neurosciences. Physiology of Nutrition and the Central 
Nervous System. Sleep Physiology. Ethnography. 
Project Title: Neuro-Nutrition as Support for Physiological Performance and Cognitive Skills 
in People with Trisomy 21, Autism Spectrum Disorders, and Attention Deficit Disorder. 
Discipline: Neurosciences. Nutrition. Neurobiology. Ethnography. Psychology. Sleep 
Physiology. 
Specialty: Physiology of Nutrition. Biochemistry. Food Allergies and Sensitivities. 
Ethnography. Sleep Physiology. Neuropsychology. Neurobiology. 
Principal Investigator: Dr. Reyes Haro Valencia 
Type of Research: Prospective longitudinal study 
Project Duration: 13 months 
Keywords: Nutrition. Feeding. Trisomy 21. Down Syndrome. Autism. Attention Deficit 
Disorder. Hyperactivity. Cognitive Development. Sleep Physiology. Biochemistry. 
Physiology. Neurotransmitters. Sleep Disorders. Social Integration. Ethnography. 
Neurobiology. Quality of Life. Dysbiosis. Polysomnography. Evoked Potentials. Sociology. 
Neuropsychology. Neurodevelopment. Disability. 
December 2021 
 
 
 
 
 
 
 
 
 
 

Institutional Alignment and Project Justification 
The present project arises from the collaborative efforts of DOMUS Instituto de Autismo 
A.C., CTDUCA Atención Integral de Personas Down I.A.P., the Instituto Mexicano de 
Medicina Integral de Sueño, and researchers from the Universidad Nacional Autónoma de 
México (UNAM). These institutions share the commitment to develop scientific research 
with social impact, particularly in vulnerable populations with neurodevelopmental 
conditions. 
The initial Neuro-Nutrition project, registered with the National Council of Science and 
Technology (CONACYT) under the title “Neuro-Nutrition as Support for Physiological 
Performance and Cognitive Skills in Individuals with Trisomy 21” (Project ID: 157118), 
provided results that exceeded expectations. These findings paved the way to broaden the 
scope of investigation and extend the benefits of nutritional intervention to other groups, 
including individuals with Autism Spectrum Disorders and Attention Deficit Disorder, with 
or without Hyperactivity (ADD/ADHD). 
The current study builds on that foundation, seeking not only to confirm previous findings in 
individuals with Trisomy 21 but also to expand scientific and clinical knowledge in 
populations with ASD and ADD/ADHD, thereby contributing to improved quality of life, 
social inclusion, and health outcomes. 
 
SYNTHESIS 
Based on an extensive literature review, multiple genetic, immunological, metabolic, 
physiological, and therapeutic management affinities have been documented among 
individuals diagnosed with Trisomy 21 (Down Syndrome), Autism Spectrum Disorders (ASD), 
and Attention Deficit Disorder with or without Hyperactivity (ADD/ADHD). This project aims 
to help regularize altered metabolic processes and improve cognitive and behavioral skills 
in these populations through the design of an appropriate diet and the formulation of a 
specialized Dietary Supplement developed specifically to address the metabolic 
deficiencies of individuals with these conditions. 
By removing harmful elements from the body and providing the appropriate nutrients, it is 
expected that participants’ quality of life will improve both in their immediate social 
environment and in their sleep performance. 
 
 

INTRODUCTION 
According to data from the Instituto Nacional de Estadística y Geografía (INEGI) and the 
Secretaría de Salud (SSA), there are currently an estimated 150,000 individuals with Trisomy 
21 (Down Syndrome) in Mexico. In relation to the population with Autism Spectrum 
Disorders (ASD), the Clínica Mexicana de Autismo estimates approximately 45,000 
individuals nationwide, with an annual growth rate of 17%. Furthermore, the Programa 
Específico de Trastorno por Déficit de Atención (SSA Report 2001–2006) estimated 1.5 
million children and adolescents with this condition, a number that could potentially double 
when including adults who continue to be affected.  
Although individuals with Autism Spectrum Disorders (ASD) and Down Syndrome continue 
to be considered vulnerable minority groups in Mexico, the increasing prevalence of 
Attention Deficit Disorder, with or without Hyperactivity (ADD/ADHD), has made this 
condition an important focus of public health. 
According to the 2010 National Population and Housing Census conducted by the Instituto 
Nacional de Estadística y Geografía (INEGI), there are 5,739,270 individuals in Mexico living 
with some form of physical or mental disability. Based on this data, approximately 30% of 
the disabled population in the country consists of individuals with Autism Spectrum 
Disorders, Down Syndrome, or Attention Deficit Disorder, with or without Hyperactivity 
(ADD/ADHD). 
Despite awareness of these statistics, limited economic, scientific, and technological 
resources have been allocated to address the specific needs of these populations. In 
addition to the social vulnerability resulting from neglect, these groups share physiological 
and metabolic characteristics that make their clinical management highly specialized and 
complex. 
Another common feature among these three populations is the global reliance on 
pharmacological treatment models, whose effectiveness is often limited unless combined 
with behavioral therapies. Stimulants such as methylphenidate and dextroamphetamine 
are among the most frequently prescribed medications for individuals with Down Syndrome, 
Autism Spectrum Disorders (ASD), and/or Attention Deficit Disorder with or without 
Hyperactivity (ADD/ADHD) (Rappley, 2005; Frohlich, Lanphear, & Epstein, 2007; Findling, 
2008). These medications act directly on neurotransmitters such as norepinephrine and 
dopamine, which are closely associated with cognition, anxiety regulation, and satiety. 
Some of the reported benefits of these medications include reduced impulsivity and 
hyperactivity, as well as improved concentration. However, their use has also been 
associated with adverse effects such as risk of dependency, fluctuations in body weight, 

severe appetite disturbances (including anorexia or obesity), impaired growth, 
gastrointestinal problems, headaches, significant sleep disorders, marked variations in 
blood pressure (Rappley, 2005; Frohlich, Lanphear, & Epstein, 2007; Findling, 2008; Najib, 
2008), and substantial hormonal imbalances. 
The potential side effects of these medications often lead patients and their legal guardians 
(parents or caregivers) to discontinue their use, turning instead to multidisciplinary 
behavioral therapies. The limited understanding of the full scope of Trisomy 21, Autism 
Spectrum Disorders (ASD), and Attention Deficit Disorders (ADD/ADHD)—combined with 
the challenges of neurostimulant treatments and the modest effectiveness of psychological 
and behavioral interventions—has prompted both researchers and families to explore 
alternative therapeutic approaches. Increasingly, the scientific community is recognizing 
nutritional factors as decisive and fundamental in the development and clinical expression 
of these conditions (Sinn, 2008; Schnoll, 2003). 
It is also important to acknowledge that society has prompted a redefinition of disability. 
Considering disability solely as a personal or individual attribute, detached from its broader 
social context, has significant implications for international taxonomies and for the 
standards used to evaluate functional impairments (Ferreira, 2006). For instance, the World 
Health Organization’s International Classification of Impairments, Disabilities, and 
Handicaps (ICIDH) conceptualizes disability primarily as the consequence of a medical 
condition—essentially, a “natural” accident. 
Research on different forms of disability has demonstrated that the family plays a central 
role in fostering behavioral and cognitive changes in affected individuals (Ramírez, 2011). 
Such changes may result from a variety of interventions, ranging from psychological 
programs to clinical protocols. However, there is a notable lack of quantitative studies 
specifically evaluating improvements in family quality of life derived from nutritional 
interventions. 
The underlying issue is that, with the growing prevalence of neurodevelopmental disorders, 
it has become increasingly important to understand and anticipate their progression, as 
they affect individuals throughout the lifespan. Evidence from studies on these 
populations—and the challenges they face during the transition to adulthood, when many 
will outlive their parents and legal guardians—must inform discussions on service provision 
and public policy planning to ensure a better quality of life. 
 
 
 

BACKGROUND – Feasibility of the Proposal 
Research Extension 
The need to implement this protocol arises from the above-expected results of a 2011 
research project supported by the Consejo Nacional de Ciencia y Tecnología (CONACYT) 
under the PROINOVA program (Project No. 157118), titled “Neuro-Nutrition as Support for 
Physiological Performance and Cognitive Skills in Individuals with Trisomy 21.” The 
theoretical basis of that project was grounded in the physiological similarities observed 
between individuals with Autism Spectrum Disorders (ASD) and those with Trisomy 21 
(Down Syndrome). 
Key findings from the previous study that support extending the nutritional intervention to 
populations with Autism Spectrum Disorders (ASD) and Attention Deficit Disorder (ADD) 
included: strengthened immune function with fewer parasitic infections; improved 
absorption of proteins, calcium, phosphorus, and iron, resulting in higher growth rates 
compared to controls; healthier cholesterol and triglyceride profiles, thereby reducing 
cardiovascular risk; more efficient digestion and decreased chronic intestinal inflammation; 
and improved intestinal motility. In addition, participants demonstrated greater 
concentration, enhanced attention, and more socially adaptive behaviors. 
Building on this evidence, and considering that the theoretical framework of the prior project 
already encompassed individuals with ASD, the present study aims to explicitly include 
them as a primary target population, alongside individuals with ADD. 
 
Etiology 
The precise causes of Autism Spectrum Disorders (ASD), Down Syndrome, and Attention 
Deficit Disorder (ADD) remain unclear. Current therapeutic approaches are primarily aimed 
at alleviating symptoms that compromise quality of life, cognitive performance, and social 
integration. Although their etiology has not been fully established, these conditions are 
widely recognized as neurodevelopmental disorders that share significant genetic, 
immunological, metabolic, and gastrointestinal characteristics. 
Genetics 
Post-mortem brain studies examining genes associated with these disorders have 
highlighted 
immunological 
convergence 
rather 
than 
differences 
limited 
to 
neurodevelopmental genes. Consistently observed findings include immune system 
depression and elevated oxidative stress, both of which influence the type and severity of 
the disorder, as well as the degree of intellectual disability (Lintas, Sacco, & Perisco, 2010). 

Mineral deficiencies—particularly calcium, magnesium, zinc, iron, and selenium—have 
also been linked to immune dysfunction. 
Another critical factor involves neuronal development and microglial function. Excessive 
glutamate release and the presence of pro-inflammatory cytokines have been documented 
in post-mortem brains of individuals with Down Syndrome and ASD, leading to impaired 
inter-neuronal communication and disruption of long-range cortical–subcortical 
connections. These disruptions are strongly associated with deficits in cognition, social 
interaction, and sensory integration (Rubenstein & Merzenich, 2003; Courchesne & Pierce, 
2005; Geschwind & Levitt, 2007; Belmonte, 2010). 
 
Metabolism 
Immune suppression in individuals with Down Syndrome, Autism Spectrum Disorders 
(ASD), and Attention Deficit Disorder (ADD) predisposes them to recurrent infections of the 
gastrointestinal tract, respiratory system, and ears. The use of antibiotics further disrupts 
the gut microbiota, exacerbating dysbiosis. This imbalance promotes Candida overgrowth, 
which contributes to the secretion of immunotoxins, intestinal wall damage, and inhibition 
of immunoglobulin A (IgA), ultimately leading to increased intestinal permeability (leaky gut). 
In Down Syndrome, intestinal sluggishness caused by hypotonia further prolongs exposure 
to pathogens. 
These intestinal alterations impair secretin production, reducing pancreatic and hepatic 
enzyme release, and thereby hindering nutrient digestion and absorption. The processing of 
complex proteins such as casein (milk) and gluten (wheat, barley, rye, oats) is 
disproportionately affected, leaving peptides only partially digested. These altered peptides 
can cross compromised intestinal and blood–brain barriers, accumulate in the temporal 
lobes—critical for language and cognition—and exert opioid-like activity. Such effects 
contribute to mood instability, sensory alterations, sleep disturbances, respiratory 
depression, reduced attention, antisocial behaviors, and academic underperformance 
(Shaw, 2008). 
Candida also interferes with carbohydrate metabolism by fermenting sugars, leading to 
three major outcomes: 
1. Reduced ATP production from glycolysis/Krebs cycle, depriving specialized cells 
(e.g., hepatocytes, neurons, pancreatic beta cells) of energy. 
2. Production of pentosidines, accelerating oxidative stress and impairing tissue 
regeneration. 

3. Creation of alcoholic byproducts in the intestine, further damaging mucosa, 
impairing enzymatic activity, and reducing vitamin B synthesis. 
 
Oxidative Stress and Allergies 
The fermentative activity of Candida in protein and carbohydrate metabolism, together with 
oxidative stress, has been associated with degenerative and autoimmune diseases such as 
Alzheimer’s disease, diabetes, fibromyalgia, and multiple sclerosis. Nutritional control and 
targeted supplementation may significantly reduce these risks in populations with Down 
Syndrome, Autism Spectrum Disorders (ASD), and Attention Deficit Disorder (ADD). 
The functional sensitivity of these groups also predisposes them to allergic or food 
sensitivity reactions, which may manifest as behavioral, psychological, and cognitive 
disturbances. 
 
Quality of Life 
Scientific research on quality of life (QoL) has expanded considerably worldwide, ranging 
from Anglo-European contexts (Roy Brown, 2000) to Latin American settings (Verduzco, 
2010). Disability is often conceptualized as the functional and social manifestation of an 
impairment, medically attributed to a natural accident or condition. However, this 
framework tends to overlook the subjective and socially constructed dimensions of 
disability (Ferreira, 2006). 
Recognizing QoL within disability contexts now requires greater emphasis on social action 
and inclusion. Understanding the interrelationship between disability and QoL is 
fundamental to promoting equitable participation and overall well-being. 
 
Sleep Physiology 
ASD and Sleep Disorders 
Studies have shown that children with Autism Spectrum Disorders (ASD) frequently 
experience sleep–wake disturbances, particularly irregular circadian rhythms (Gail, 2004). 
While many findings are derived from parent-reported questionnaires, objective 
assessments such as actigraphy and polysomnography have confirmed abnormalities in 
sleep architecture (Allik & Malow, 2006; Goldman & Souders, 2009). Reported prevalence 
rates of sleep disorders in ASD range from 44% to 83% (Gail, 2004). 

Genetic anomalies affecting melatonin synthesis and signaling are considered central to 
these disturbances. Clinical studies indicate that melatonin administration can improve 
total sleep time, reduce sleep latency and nighttime awakenings, and enhance daytime 
behavior, with minimal adverse effects (Richdale, 1995; Wright, 2010; Rossignol, 2011; Leu, 
2010). 
ADD and Sleep Disorders 
In children with suspected Attention Deficit Disorder (ADD), evaluation of sleep is crucial, 
as sleep disturbances can exacerbate ADD symptoms. Some children initially diagnosed 
with ADD may in fact present with primary sleep disorders such as sleep apnea or restless 
legs syndrome (Mindell, 2003). Sleep and attention are bidirectionally linked, sharing 
common prefrontal cortex mechanisms (Dahl, 1996; Kirov, 2004). The prevalence of sleep 
disturbances in ADD is higher than in both healthy controls and psychiatric controls (Ball, 
1997; Stein & Corkum, 1999). 
Experimental studies on sleep deprivation have confirmed that reduced sleep worsens 
attention and executive performance (Kim, 2011; Prihodova, 2010; Touchette, 2009). 
Adequate sleep, by contrast, has been associated with better motor skills, reaction times, 
and REM/N3 sleep architecture (Prehn-Kristensen, 2011). Meta-analyses estimate that up 
to 70% of children with ADD experience sleep disorders, with consequences for cognitive 
functioning, school attendance, parental mental health, and family dynamics (Sciberras, 
2010; O’Callaghan, Meltzer, & Chiang, 2010). 
Behavioral sleep interventions—such as sleep hygiene programs—have shown positive 
outcomes. When insufficient, melatonin supplementation may be considered, with 
evidence supporting the effectiveness of combining behavioral and pharmacological 
approaches (Weiskop, 2005; Hannah & Malow, 2009). 
 
Previous Dietary Supplements 
Historical attempts at dietary supplementation for Down Syndrome include: 
• 
1940s (USA, Dr. Henry Turkel): A mix of 48 vitamins, minerals, and hormones. No 
proven long-term benefits were reported (Turkel, 1975). 
• 
1960s (Germany, Dr. Habound): A vitamin–hormone–enzyme mix with no confirmed 
effectiveness (Habound, 1955). 
• 
1980s (USA, Dr. Ruth Harrell): A supplement of vitamins, minerals, and thyroid 
hormone showed preliminary IQ improvements in three Down Syndrome patients 

(Harrell, 1981), but results were not replicated. Commercial versions like “Haps 
Caps” remain unsubstantiated by scientific studies. 
• 
1990s (USA, Dixie Lawrence Tafoya): Building on Turkel’s formula, MSB Plus was 
tested on her adopted daughter with Down Syndrome. Despite anecdotal 
improvements, it lacked scientific support. The product evolved into MSB V7 (Nutri-
Chem Labs) and later NuTriVene-D (International Nutrition), now marketed with 
modifications but still lacking independent clinical evidence. 
For ASD and ADD populations, examples include: 
• 
Formula One Supplement (Singapore, Autism Recovery Center): Marketed as 
detoxifying and calming, but without scientific validation. 
• 
Kirkman Laboratories (USA): Offers a broad line of supplements categorized by 
function (antioxidant, digestive, immune, sleep, cognition/attention, etc.). Despite 
popularity, no peer-reviewed studies confirm their effectiveness. The company itself 
notes: “These nutritional statements have not been evaluated by the Food & Drug 
Administration. This product is not intended to diagnose, treat, cure, or prevent any 
disease.” 
 
JUSTIFICATION 
T-2 investigational nutritional formulation (research use only) 
The T-2 investigational nutritional formulation, developed within the framework of this 
research, is a functional food formulated to support the nutritional management of 
individuals with Trisomy 21 (Down Syndrome), Autism Spectrum Disorders (ASD), and 
Attention Deficit Disorder (ADD/ADHD). Because of the distinctive characteristics of their 
immune systems, these individuals are particularly susceptible to intestinal dysbiosis, 
which disrupts metabolic pathways and exacerbates the biochemical imbalances inherent 
to these conditions. The T-2 investigational nutritional formulation provides naturally 
sourced nutrients in bioavailable forms that can be metabolized by dysbiotic intestines to 
help restore disrupted metabolic processes. 
It is important to emphasize that the T-2 investigational nutritional formulation is not a 
complete food. Rather, it is designed as nutritional support specifically aimed at mitigating 
intestinal dysbiosis in individuals with the above-mentioned neurodevelopmental 
disorders. It is not intended as a treatment and does not seek to reduce intellectual 
disabilities or correct neurological deficits. For these reasons, it cannot be considered a 
drug or medication. 

The T-2 formulation is formulated as a synergistic system, in which its specific ingredients 
interact to transform into bioactive forms that can be effectively absorbed by an organism 
compromised by dysbiosis. Its components function as precursors to one another, ensuring 
bioavailability in individuals with impaired metabolic function. When taken separately, 
these elements would not achieve the same therapeutic effect as when combined in the 
precise balance provided by the T-2 formulation. 
 
Qualitative Description of Ingredients 
The scientific name of this sugar is 6-O-α-D-glucopyranosyl-D-fructofuranose, a 
disaccharide that occurs naturally in honey, sugar cane, beets, and certain fruits, though 
only in trace amounts. For this reason, it is commercially produced from food-grade sucrose 
through an enzymatic rearrangement that converts its glycosidic bond from 1,2-fructosyl to 
1,6-fructosyl (Lina, Jonker, & Kozianowski, 2002). 
While its properties are similar to sucrose, isomaltulose presents several important 
differences: it has approximately 50% of sucrose’s sweetness, a lower melting point, and 
greater stability under acidic conditions, making it more resistant to microbial fermentation. 
Isomaltulose is absorbed more slowly than sucrose and is completely hydrolyzed in the 
small intestine, resulting in lower plasma glucose and insulin peaks. A 1985 study 
conducted at the University of Tsukuba showed that plasma glucose following isomaltulose 
ingestion rose gradually over 60 minutes to 110.9 mg/dl and then remained stable for two 
hours. By contrast, sucrose ingestion produced a rapid peak of 143.3 mg/dl within 30 
minutes, followed by a sharp decline. These results were consistent even among individuals 
with diabetes, supporting isomaltulose as a suitable sweetener for this population (Kawai, 
Okuda, & Yamashita, 1985). 
The complete hydrolysis of isomaltulose in the small intestine has been further 
demonstrated in urinary excretion studies, confirming that its breakdown products, glucose 
and fructose, are fully metabolized and absorbed (Menzies, 1974). 
Isomaltulose has been extensively studied, with findings demonstrating that its 
consumption promotes fat oxidation both at rest and during exercise, thereby sparing 
glycogen reserves and reducing body fat mass without compromising systemic function 
(König, Theis, Kozianowski & Berg, 2011). 
Further studies conducted at the University of Sydney reported that Isomaltulose has a 
glycemic index of 32, classified as very low, and provides sustained energy without abrupt 
glucose fluctuations. Its hydrolysis in the small intestine occurs four to five times more 
slowly than that of sucrose, prolonging energy release.  

Because of these properties, Isomaltulose is widely used in sports nutrition, diabetic-
friendly foods, and as a sucrose substitute. It does not ferment in the gut, thereby avoiding 
bacterial overgrowth—particularly of Candida—and enhances nutrient absorption when 
consumed in solution. 
 
Whey Protein Concentrate 
Proteins are essential nutrients, second only to water in abundance in the human body. They 
are the fundamental components of muscles, vital organs, blood cells, enzymes, and 
hormones (Herman, 2009). Structurally, proteins are chains of amino acids; there are 20 in 
total, 9 of which are essential and must be obtained from the diet. 
Animal-based proteins typically provide all essential amino acids in balanced proportions, 
whereas plant-based proteins require careful combination to achieve adequacy. Protein 
quality is evaluated through indices such as Biological Value (BV) and the Protein 
Digestibility Corrected Amino Acid Score (PDCAAS), the latter having been the preferred 
method of assessment by both the FDA and WHO since 1993. 
The primary role of protein is to support tissue repair and maintenance. When consumed in 
excess, protein can also serve as a precursor for energy production through the Krebs cycle 
(Meléndez-Hevia, Waddell & Cascante, 1996). Conversely, insufficient intake compromises 
tissue integrity. 
In individuals with Down Syndrome, Autism Spectrum Disorders (ASD), or Attention Deficit 
Disorder (ADD), metabolic deficiencies—including allergies or sensitivities—may impair the 
hydrolysis of certain animal proteins (such as casein, albumin, and red meat proteins) as 
well as plant proteins like gluten (Shaw, 2008). 
The whey protein incorporated into the T-2 investigational nutritional formulation provides 
all essential amino acids with high bioavailability and closely resembles the composition of 
human breast milk, making it highly efficient and particularly beneficial for individuals with 
intestinal dysbiosis. As a pure whey protein concentrate, it carries no allergenic risk.  
 
Flaxseed 
The use of flaxseed as a functional food dates back centuries, particularly in European 
bread-making traditions. Modern studies in the United States have confirmed its health 
benefits. Flaxseed varieties suitable for human consumption include brown and golden, 

with an average composition of 41% fat, 20% protein, 28% dietary fiber, 7.7% moisture, and 
3.4% ash (Morris, 2007). 
Its protein profile is similar to soy but lacks sulfur double bonds that hinder digestion. 
Flaxseed oil is rich in polyunsaturated essential fatty acids, including alpha-linolenic acid 
(Omega-3), linoleic acid (Omega-6), and oleic acid (Omega-9). Omega-3 fatty acids are 
metabolized into EPA and DHA with the assistance of vitamins B3, B6, C, E, and A, along with 
minerals such as magnesium and zinc. EPA supports the production of anti-inflammatory 
prostaglandins, while DHA serves as a structural component of the brain, retina, and sperm, 
and is a precursor to neurotransmitters such as serotonin and acetylcholine. In contrast, 
Omega-6 metabolism leads to arachidonic acid and pro-inflammatory prostaglandins, 
which must be balanced by Omega-3 derivatives (Schmidt, 1997). 
Western diets often present an Omega-6 to Omega-3 ratio of approximately 20:1, 
inadequate for optimal EPA and DHA synthesis, and potentially contributing to the 
prevalence of cardiovascular diseases. Beyond its fatty acids, flaxseed provides soluble and 
insoluble fiber, which promotes satiety, supports glucose regulation, improves bowel 
motility, and contributes to lipid reduction (Morris, 2007). 
Flaxseed also contains phenolic compounds with antioxidant activity, including phenolic 
acids, flavonoids, and lignans, which have been studied for their role in cancer prevention 
(Jacobs & White, 1998; Sonnenberg & Müller, 1993; Kune et al., 1998). Another component, 
gamma-tocopherol, acts as an antioxidant, supports blood pressure regulation, and may 
help prevent cardiovascular disease, cancer, and Alzheimer’s disease (Chandan, Savita & 
Sashwati, 2006; Daun & Przybylski, 2000; Morris et al., 2005). 
In addition, flaxseed contains vitamins C, B-complex, carotenoids, vitamin E isoforms, and 
vitamin K, which is essential for blood clotting and bone mineralization (Berkner & Runge). 
Its mineral profile includes calcium, copper, magnesium, manganese, phosphorus, 
potassium, sodium, and zinc. 
The flaxseed incorporated into the T-2 investigational nutritional formulation is milled 
golden flaxseed and is sourced from golden flaxseed harvested at peak maturity. Its 
specialized processing preserves fat micelles and maximizes antioxidant content, 
particularly lignans, providing 10 mg per gram, equivalent to approximately 30% of the daily 
antioxidant requirement. Milled golden flaxseed also offers a favorable Omega-6 to Omega-
3 ratio (2:3), which supports neurotransmitter production and contributes to overall 
metabolic balance. 
 
Milk Serum Mineral Complex 

Calcium is a vital mineral, with 99% of the body’s stores located in bones and teeth. It also 
plays an essential role in muscle contraction, blood clotting, and nerve transmission. 
Inadequate calcium intake during childhood and adolescence compromises bone 
development, as nearly half of total bone mass is formed during these life stages. 
The calcium included in the T-2 investigational nutritional formulation is obtained through 
ultrafiltration of milk serum, a process that preserves its natural nutrient balance. Its 
composition closely resembles that of human bone. The FDA has recognized several health 
claims for milk-serum mineral complex, including its role in promoting bone health, 
supporting postmenopausal women, enhancing calcium absorption, and preventing 
osteoporosis (Ward, 2007). 
Milk-serum mineral complex also demonstrates high solubility in acidic environments, 
ensuring superior bioavailability. This enhances cellular nutrient uptake and potentiates the 
absorption of other nutrients present in the T-2 formula. 
Short-Chain Fructooligosaccharides (scFOS) 
Short-chain fructooligosaccharides (scFOS) are composed of fructose molecules with a 
terminal glucose unit. They occur naturally in foods such as onions, asparagus, garlic, oats, 
rye, and artichokes, and are resistant to digestion in the upper gastrointestinal tract. Once 
they reach the colon, they are fermented by the microbiota and act as prebiotics. 
Human studies have demonstrated that scFOS intake can increase bifidobacteria 
populations up to tenfold, while simultaneously suppressing pathogenic microorganisms 
such as Clostridia and Candida (Molis et al., 1996; Mitsuoka, Hidaka & Eida, 1987). Their 
prebiotic role has been formally recognized by both the World Health Organization (WHO) 
and the Food and Agriculture Organization (FAO) (2001), highlighting their contribution to gut 
health through selective microbial modulation. 
Additional benefits of scFOS include enhanced absorption of calcium, magnesium, and 
copper (Van Den Heuvel et al., 1999; Tahiri et al., 2001; Ducros et al., 2005). 
The scFOS incorporated into the T-2 investigational nutritional formulation is derived from 
sucrose oligomers through enzymatic processes using non-GMO Aspergillus japonicus.  
More than 200 studies have confirmed that scFOS promotes the growth of bifidobacteria 
and lactobacilli, restores intestinal balance, enhances nutrient absorption, and improves 
mineral utilization. It has also been shown to support cholesterol and triglyceride reduction, 
accelerate gastrointestinal transit, and contribute to overall health. 
 

Lactoferrin 
Lactoferrin is a globular glycoprotein (peptide) responsible for transporting and delivering 
iron to cells, thereby regulating the presence of free iron in the bloodstream and in biological 
secretions. It exists in two forms: holo-lactoferrin (iron-saturated) and apo-lactoferrin (iron-
free) (Levay & Viljoen, 1995). 
Beyond its role in iron binding and transport, lactoferrin can also associate with other metals 
such as copper, zinc, manganese, gallium, and vanadium (Davidson & Lönnerdal, 2007). Its 
affinity for iron is approximately 300 times greater than that of transferrin, another plasma 
glycoprotein that regulates iron levels in biological fluids. This affinity increases in acidic 
environments, explaining its interaction with transferrin during inflammatory processes, 
when tissue pH decreases due to the secretion of lactic acid and other metabolites. 
Lactoferrin is a critical component of the immune system owing to its bactericidal, 
fungicidal, and antiviral properties. It is present on mucosal surfaces and constitutes a 
major component of several secretions, including bile, saliva, pancreatic fluid, and semen, 
making it a key element of epithelial defense barriers. Numerous studies have 
demonstrated its effectiveness in combating intestinal infections caused by Escherichia 
coli. 
Its antimicrobial activity is linked to its ability to sequester iron, acting as a natural 
bacteriostatic agent. In addition, lactoferrin exerts direct microbicidal effects by damaging 
microbial membranes through cytoplasmosis, thereby impairing permeability and 
disrupting cellular respiration in pathogens. 
Although its fungicidal properties are less extensively studied, lactoferrin is known to 
combat Candida infections by acting synergistically with leukocytes to inhibit fungal 
reproduction. Its antiviral activity is primarily achieved by blocking viral attachment to host 
cells, thereby preventing entry and replication. This effect has been documented against 
several viruses, including hepatitis, rotavirus, leukemia viruses, and herpes. 
Humans receive their highest dose of lactoferrin through colostrum, the first maternal milk 
produced after childbirth. Human milk contains the greatest concentration of lactoferrin of 
all mammalian milks, with colostrum containing approximately three times more than 
mature milk (Nagasawa, Kiyosawa & Kuwahara, 1972). After human milk, cow’s milk 
provides the next richest source. 
The lactoferrin included in the T-2 investigational nutritional formulation is sourced from 
cow’s milk. It is extracted from whey using a process that preserves its bioactivity. 
Documented properties include immune modulation, stimulation of intestinal cell growth, 

antimicrobial action, iron transport, inhibition of intestinal dysbiosis, and suppression of 
fungal overgrowth in the oral and gastrointestinal tract (Ward, 2006). 
 
Pyridoxine Hydrocloride (Vitamin B6) 
Vitamin B6, also known as pyridoxine, is one of the eight vitamins in the B-complex group. 
Collectively, B vitamins are essential for converting carbohydrates into glucose—the body’s 
primary energy source via the Krebs cycle—and are also involved in lipid and protein 
metabolism. 
Specifically, Vitamin B6 plays a central role in brain development and function. It serves as 
the primary cofactor for the enzymes delta-5-desaturase and delta-6-desaturase, which are 
required for the breakdown of omega-6 and omega-3 fatty acids into critical 
neurotransmitters, 
including 
serotonin, 
epinephrine, 
norepinephrine, 
dopamine, 
melatonin, and gamma-aminobutyric acid (GABA). Together with Vitamin B12, it is also 
indispensable for the production of erythrocytes (red blood cells) and leukocytes (white 
blood cells), the latter being key components of the immune system. 
Vitamin B6 is metabolized primarily in the liver, jejunum, and ileum, exerting much of its 
activity through the digestive system before being distributed to other tissues. Functionally, 
it acts as a coenzyme in the synthesis of hemoglobin, histamine, neurotransmitters, and in 
the metabolism of lipids, glucose, and amino acids. 
The T-2 formulation includes pyridoxine hydrochloride (vitamin B6). 
 
Systemic Functioning of the T-2 investigational nutritional formulation 
The T-2 investigational nutritional formulation acts on multiple metabolic pathways and 
biochemical processes, not only through the properties of its individual components but 
also through their synergistic interactions, which enhance systemic balance across organs 
and tissues. 
Isomaltulose, being enzymatically rather than bacterially hydrolyzed, is not a viable 
substrate for pathogenic microorganisms such as Candida. This property reduces parasitic 
colonization throughout the gastrointestinal tract and helps prevent nutrient malabsorption. 
In combination with lactoferrin, which provides antimicrobial protection at entry points such 
as the oral cavity, the investigational formulation establishes protective conditions from 
ingestion onward. 

The strong glycosidic bond of Isomaltulose ensures sustained energy release, avoiding 
abrupt glucose spikes and subsequent hypoglycemic crashes. Unlike sucrose, which is 
rapidly fermented by bacteria, Isomaltulose supports a balanced supply of glucose and 
glycogen, stabilizes insulin secretion, and reduces anxiety, thereby contributing to improved 
learning, concentration, emotional regulation, and appetite control. 
Its synergy with milled golden flaxseed flaxseed further promotes fat metabolism by 
encouraging the body to utilize fat reserves when carbohydrate absorption is slowed. 
Together, Isomaltulose, flaxseed, and scFOS promote the restoration of intestinal balance 
by stimulating the growth of beneficial bifidobacteria and lactobacilli, improving nutrient 
absorption, and optimizing osmolarity (170–295 mOsm/L). 
Whey protein concentrate whey protein supports the repair of intestinal lesions caused by 
Candida and Clostridia. This is particularly relevant given that the small intestine produces 
up to 95% of the body’s serotonin and 50% of its dopamine (Manocha et al., 2012; Gershon, 
1999; Mirre, 2012). By restoring intestinal integrity, Whey protein concentrate enhances 
neurotransmitter production, with synergistic effects amplified by milk-serum mineral 
complex calcium and flaxseed-derived vitamin K, both of which are essential for bone health 
and blood coagulation. 
Milled golden flaxseed flaxseed provides 1.09 g of dietary fiber per serving, which 
contributes to improved intestinal motility and helps maintain microbiota balance. Its fatty 
acid profile ensures the sequential metabolic conversion of oleic acid (omega-9), linoleic 
acid (omega-6), and alpha-linolenic acid (omega-3) into arachidonic acid, EPA, DHA, and 
prostaglandins, thereby supporting inflammatory regulation and cerebral blood flow. 
 
Dosage and Administration 
 
Participants will be instructed to take 23 g of the T-2 investigational nutritional formulation, 
twice daily, dissolved in 250 ml of liquid. 
For the study population (Trisomy 21, ASD, and ADD/ADHD), it is recommended that the 
investigational formulation be prepared with Casein-free beverage, which is casein-free and 
enriched with probiotic fiber. However, it may also be consumed with other liquids—
including cow’s milk, plant-based beverages, coffee, tea, water, or natural juice—without 
altering its properties. The formulation can be taken hot, cold, or warm. 

The first daily dose should be consumed upon waking, ideally 30–60 minutes before 
breakfast. The second dose should be taken in the afternoon, approximately two hours 
before sleep, regardless of dinner timing. 
 
Ethnography 
Studying quality of life (QoL) in families with a member diagnosed with Autism Spectrum 
Disorders (ASD), Attention Deficit Disorder (ADD/ADHD), or Trisomy 21 (Down Syndrome) is 
a central aspect of this research. Such analysis makes it possible to assess not only the 
progress of participants undergoing nutritional intervention but also the broader impact on 
family dynamics. 
In recent years, QoL has gained increasing importance due to the limited opportunities for 
social, 
family, 
and 
leisure 
activities, 
particularly 
in 
households 
managing 
neurodevelopmental conditions. Evidence from the initial phases of this line of research has 
demonstrated that nutritional interventions can strengthen specific abilities in individuals 
with disabilities while also enhancing the overall well-being of their families. 
These outcomes justify expanding the scope of investigation from ethnographic exploration 
to sociological analysis, providing valuable insights into the cognitive and behavioral 
evolution of participants, as well as the adaptive changes within their families over the 
course of one year. 
 
Sleep Physiology 
This study aims to evaluate a balanced dietary intervention formulated with Isomaltulose, 
whey protein concentrate, flaxseed, milk-serum mineral complex, scFOS, Luo Han Guo (as 
a natural sweetener), and lactoferrin. The impact of this intervention on children with 
Trisomy 21 (Down Syndrome), Autism Spectrum Disorders (ASD), and Attention Deficit 
Disorder (ADD/ADHD) will be objectively assessed through neurophysiological testing and 
blood chemistry analyses. 
Given that sleep disorders are highly prevalent in these populations and that diet is known 
to influence symptom expression, this project also seeks to explore the interplay between 
diet, sleep, and behavior. By addressing this understudied area, the study aims to generate 
evidence that can inform more comprehensive management strategies for children with 
neurodevelopmental conditions. 
 

Neuropsychological 
Down Syndrome (DS) is the most common genetic cause of intellectual disability (ID), 
defined as an IQ below 70. Severity is typically classified as mild (IQ 55–70), moderate (IQ 
40–54), severe (IQ 25–39), or profound (IQ < 25) (Vaillend et al., 2008). Approximately 30% of 
moderate to severe cases of intellectual disability are associated with DS (Stoll et al., 1990; 
Pulsifer, 1996). 
Intellectual disability in DS impacts multiple domains, including cognitive development, 
language acquisition, motor skills, learning, and memory (Brown et al., 1990; 2003; Raz, 
1995; Pulsifer, 1996; Hodapp et al., 1999; Chapman et al., 1998; Carlesimo et al., 1997; 
Clark & Wilson, 2003; Nadel, 2003; Pennington et al., 2003). 
Although IQ testing has traditionally been the primary diagnostic tool, current 
recommendations emphasize the use of comprehensive assessments that incorporate 
daily living skills, cognitive processes, and emotional functioning, employing tools that are 
both culturally and linguistically adapted (Rondal, Perera & Spiker, 2011; Edgin et al., 2010). 
 
HYPOTHESIS 
Through a biomedical protocol involving dietary intervention and nutritional reinforcement 
with the T-2 investigational nutritional formulation, formulated for individuals with Down 
Syndrome (DS), Autism Spectrum Disorders (ASD), and Attention Deficit Disorder 
(ADD/ADHD), it is anticipated that intestinal dysbiosis, pathogenic burden (bacteria, fungi, 
yeasts), and oxidative stress will be reduced. This intervention is expected to promote a 
balanced nutritional state and support the production of key neurotransmitters, thereby 
contributing to improvements in quality of life, sleep regulation, concentration, cognition, 
self-regulation, and social interactions.Secondary Hypothesis 
Oral administration of T-2 in mice will increase dendritic spines and synapses and improve 
performance in motor and cognitive tasks. 
OBJECTIVES 
• Improve compromised metabolic processes inherent to these conditions, as 
reflected in indicators such as dysbiosis, infections, food sensitivities, malnutrition, 
thyroid function, and neurotransmitter utilization. 
• Strengthen the immune system, reducing allergies, sensitivities, otic and respiratory 
infections, and gastrointestinal pathogens. 

• Reduce oxidative stress, leading to decreased anxiety, improved sleep quality, and 
enhanced Krebs cycle efficiency. 
• Enhance gastrointestinal function and nutrient absorption, assessed through 
markers such as reflux, cholesterol and triglyceride levels, bowel regularity, stool 
formation, and improvements in body mass index (BMI). 
• Improve quality of life, including stabilization of mood, increased social interactions, 
and reinforcement of cognitive processes such as attention, adaptability, and 
concentration. 
 
Secondary Objectives 
• Ethnography: Quantify the impact of the nutritional intervention on families of 
individuals with Trisomy 21, Autism Spectrum Disorders (ASD), and Attention Deficit 
Disorder (ADD/ADHD), with particular attention to changes in family dynamics 
across different phases of the study. 
• Sleep Physiology: Investigate the relationship between diet and sleep in children with 
ADD and ASD, evaluating the effectiveness of dietary modification on sleep patterns 
and expression. 
 
CONTRIBUTION OF THE PROJECT TO ADVANCING KNOWLEDGE IN ITS OWN FIELD 
AND AREA OF RESEARCH 
This project represents the first biomedical protocol in Mexico to investigate neuro-
nutrition—defined as dietary intervention combined with nutritional enrichment—in 
populations with Autism Spectrum Disorders (ASD) and Attention Deficit Disorder 
(ADD/ADHD), while also expanding upon the findings previously obtained in the first stage 
of this protocol with individuals with Trisomy 21 (Down Syndrome). 
The primary aim is to provide both quantitative and qualitative evidence that disability in 
individuals with DS, ASD, and ADD extends beyond intellectual impairment into biological 
domains. 
The project further seeks to enhance understanding of the metabolic and physiological 
characteristics of these populations, thereby informing the design of appropriate 
therapeutic management strategies. 

Finally, it intends to demonstrate that ADD encompasses neurobiological, electrical, and 
biochemical processes, extending beyond the psychosocial dimensions traditionally 
emphasized. 
 
METHODOLOGY 
Operational Duration 
The project will run for a period of 13 months. 
Population Description 
The estimated total population is 72 individuals between 2 and 35 years of age, divided into 
three groups based on their neurodevelopmental condition: 
• 
Trisomy 21 (Down Syndrome, DS) 
• 
Autism Spectrum Disorder (ASD) 
• 
Attention Deficit Disorder (ADD) 
Each group included between 24 and 27 participants, with more males than females. Ages 
ranged from 2–33 years for ASD, 2–30 years for DS, and 5–14 years for ADD. Mean ages and 
BMI values are shown in Table 1. 
Participants 
    ASD 
(N = 27) 
ADD 
(N = 25) 
DS 
(N = 24) 
Mean (SD) 
Mean (SD) Mean (SD) 
Age (years)  
2-33 
11.51±8.5 
5-14 
8.8±2.32 
 
2-30 
13.7±7.25 
Body mass index (kg/m2) 
19.11±3.71 
18.41±4.01 21.92±6.27 
Men 
24 
20 
14 
Women 
3 
5 
10 
Table 1. Characteristics of each group 
For participants with Autism Spectrum Disorders (ASD), recruitment was conducted at 
DOMUS Instituto de Autismo A.C., where diagnoses were confirmed using DSM-IV criteria 
(First et al., 2002). Symptom severity was assessed with the IDEA (Inventario del Espectro 
Autista-Autism Spectrum Inventory), which evaluates 12 developmental dimensions across 
four areas and is scored on a scale from 0 to 8. Scores between 70–96 indicate classic 
Kanner autism, 50–70 correspond to regressive autism, 40–50 reflect high-functioning 

autism, and 30–45 indicate Asperger’s syndrome (Martos & Morueco, 2007; García-López & 
Narbona, 2014b). The mean IDEA score for this sample was 63 ± 18 (Table 2). 
 
Diagnostic (DSM-IV) 
IDEA (Autism Spectrum Inventory) 
ASD N = 27 
Pervasive Developmental Disorders (PDD): 
Autistic Disorder – 74% 
Pervasive Developmental Disorders, Not 
Otherwise Specified (PDD-NOS) – 26% 
Classic Kanner Autism (70–96) – 40% 
“Regressive Autism” (50–70) – 40% 
High-Functioning Autism (40–50) – 4% 
Asperger’s Syndrome (30–45) – 16% 
Table 2. Diagnosis and IDEA scores in ASD participants 
For participants with Attention Deficit Disorder (ADD/ADHD), recruitment was conducted 
through schools specializing in this condition. Diagnosis was confirmed using the Conners’ 
Parent Rating Scale – Revised (Long Form), which assesses behavioral and learning 
difficulties, psychosomatic complaints, impulsivity, hyperactivity, and anxiety (Conners, 
1999). The Hyperactivity Index was applied, with scores greater than 16 for boys and 12 for 
girls aged 6–11 indicating clinically significant hyperactivity (Orjales Villar, 1998) (Table 3). 
Check list DSM-IV 
Hyperactivity Index 
Conners Revised Scale 
 
ADD 
N = 25 
Girls (n=4) with suspected 
ADD (>12) 
50 % 
 
Boys (n=21) with suspected 
ADD (>16) 
33 % 
Table 3. Conners’ Scale results for ADD participants 
For DS, participants came from “CTDUCA Atención Integral de Personas Down IAP” and 
“Integración Down IAP.” All had karyotype-confirmed diagnoses, with one case of 
mosaicism. 
 
Population Segregation 
Each diagnostic group was further divided into three subgroups: 
• 
Pilot Group: Received 23 g of T-2 twice daily and followed a strict dietary 
intervention protocol. 
• 
Diet Group: Followed the dietary intervention protocol without supplementation. 
• 
Control Group: Received neither supplementation nor dietary intervention. 

The study population (ages 2–35) was further stratified into subgroups A–G (3–30 years) 
according to developmental stages (Figure 6: Age distribution). 
 
Subgroup 
Lower limit 
Upper limit 
A 
3 
5 
B 
6 
9 
C 
10 
13 
D 
14 
17 
E 
18 
21 
F 
22 
25 
G 
26 
30 
Figure 6. Population distribution by age groups 
 
Clinical Evaluation 
Clinical follow-ups included parental reports and physical examinations aimed at detecting 
allergies, food sensitivities, candidiasis, infections, gastrointestinal disturbances, chronic 
otitis media, and other recurrent conditions. A 25-item checklist was applied, covering 
digestive, respiratory, dermatological, and systemic indicators. 
 
Laboratory Studies 
Laboratory support included: 
• 
Blood count: red/white series, platelets, sedimentation. 
• 
Blood chemistry: glucose, urea, creatinine, uric acid, lipids, triglycerides. 
• 
C-reactive protein: marker of inflammation. 
• 
Serum homocysteine: marker of fat metabolism and oxidative stress. 
• 
Plasma cortisol: indicator of adrenal activity. 
• 
Thyroid panel: T4, free T4, T3, protein-bound iodine, TSH, total cholesterol. 

• 
Stool analyses: coprological, coproparasitoscopic (3 samples). 
Some specialized biochemical analyses were conducted at The Great Plains Laboratory 
(Kansas, USA), led by Dr. William Shaw, including: 
• 
IgG Food Allergy Panel (93 foods). 
• 
Comprehensive Organic Acid Test (65 metabolites). 
• 
Urinary peptides from gluten and casein. 
 
Anthropometrics 
Weight, height, and BMI were measured monthly, compared against WHO growth standards 
(BMI-for-age) and Mexican NOM references (NOM-008-SSA2-1993; NOM-174-SSA1-1998). 
 
Ethnography 
The study adopted a longitudinal approach using the Sherlock model, combining 
quantitative and qualitative assessments of personal, functional, and social quality of life. 
Families underwent three structured interviews (baseline, mid-study, final), recorded in 
audio and video, with statistical and content analysis applied to results. 
 
Neuropsychology 
IDEA Inventory (ASD): Applied to establish severity, guide interventions, and assess 
treatment impact across 12 dimensions. 
Down Syndrome: Cognitive assessments emphasized daily life skills, cognitive processes, 
and emotional capacities. Recommended tests were culturally and linguistically adapted 
(Rondal, Perera & Spiker, 2011; Edgin et al., 2010). Tools included: 
• 
Ages 3–6: BATELLE developmental inventory (Newborg et al., 1998). 
• 
Ages 6–35: NEUROPSI Attention and Memory (Ostrosky et al., 2003), Executive 
Function Battery (Flores et al., 2008, 2011), computerized neuropsychological tasks 
(Ostrosky et al., 2003), basic emotion recognition tasks, Barthel Index (Cid-Ruzafa & 
Damián-Moreno, 1997), and BRIEF executive function scale (Goia et al., 2000). 
The neuropsychological evaluation was coordinated by Dr. Maura Jazmín Ramírez Flores, 
with support from trained psychology interns (4–6 students). 

ADD: NEUROPSI Attention and Memory (6–85 years), EDAH (for ADHD), and Conners’ 
Scales (long parent version, 80 items) were applied. 
 
Polysomnography and P300 
Polysomnographic assessments included recordings of EEG, EOG, EMG, heart rate, 
respiratory effort, airflow, oxygen saturation, limb movements, and sleep architecture. Data 
were analyzed according to international standards and compared with control groups 
using ANOVA. 
Measured variables included total sleep time, wake time, sleep efficiency index, distribution 
of sleep stages, number of awakenings, apnea–hypopnea index, and periodic limb 
movement index. Additionally, P300 event-related potentials were incorporated as an 
independent clinical measure. 
All studies were conducted at a specialized sleep clinic in Mexico City, and participants 
received dietary support throughout the study period. 
 
Family Seminars 
To support families and disseminate the objectives of the study, a series of educational 
seminars was organized. Topics addressed included candidiasis, allergies, biomedical 
protocols, psychological adaptation to disability, family dynamics, and nutritional 
interventions (e.g., gluten-free diets, food additives, and cooking classes). 
The sessions were delivered by Dr. Javier Hernández Covarrubias, Psychologist María 
Angélica Núñez, and Biochemical Engineer Cecilia Fernández Aguirre. 
 
 
BENEFITS AND RISKS FOR THE POPULATION 
This is considered a minimal-risk study, as supplementation does not pose a health risk and 
does not involve pharmaceutical compounds. 
Risks associated with sample collection, electrophysiological studies, and psychological 
testing will be managed by the professional staff of the Instituto Mexicano de Medicina 
Integral de Sueño. In all cases, follow-up will be provided by a multidisciplinary medical 

team that includes specialists in Otorhinolaryngology, Psychology, Geriatrics, Dentistry, 
Pediatrics, Neurology, Psychiatry, Pulmonology, and Internal Medicine. 
All participants will receive reports from their clinical assessments, evaluations, and 
electrophysiological studies, along with specialized counseling. Any conditions requiring 
medical care will be addressed and followed up by qualified medical professionals. 
 
ASSIGNMENT OF RESPONSIBILITIES: RESEARCH TEAM AND ASSOCIATED ENTITIES 
Professional Staff 
• 
Dr. Reyes Haro Valencia – Principal Investigator (CONACYT CVU: 74747) 
• 
Dr. Elizabeth Ibarra Coronado – Sleep Physiology Area Leader (CONACYT CVU: 
288056) 
• 
I.Q.I. Edilberto Sánchez – Technical Coordinator (CONACYT CVU: 392429) 
• 
Eng. Miguel Hidalgo Olvera – Legal Representative and Administrative Coordinator 
(CONACYT CVU: 392684) 
• 
Lic. Mónica Matilde Apodaca Aragón – Project Administrator (CONACYT CVU: 
499625) 
• 
I.B. Cecilia Fernández Aguirre – Biomedical Area Leader (CONACYT CVU: 353604) 
• 
Dr. Octavio César García González – Neurobiology Area Leader (CONACYT CVU: 
39694) 
• 
Dr. Maura Jazmín Ramírez Flores – Neuropsychological Evaluation for Down 
Syndrome (CONACYT CVU: 174346) 
• 
Lic. Juana Elvira Portillo Navarro – Neuropsychological Evaluation for ADD 
(CONACYT CVU: 510484) 
• 
Arturo Ramírez Ramos – Ethnographic Area Leader (CONACYT CVU: 510634) 
Institutional Site 
Instituto Mexicano de Medicina Integral de Sueño 
Associated Entities 
• 
Mexico: Olarte y Akle Bacteriólogos, S.A. de C.V. 
• 
United States: The Great Plains Laboratory, Inc. 

• 
Integración Down, I.A.P. 
• 
Domus Instituto de Autismo 
 
PROGRESS CONTROL PLAN 
The project is scheduled to last 13 months, from December 2021 to December 2022, and 
will be divided into two stages of approximately six months each. 
 
Stage I: Design and Intellectual Property Protection 
Duration: First Semester 
Objectives: 
• Confirm the physiological and metabolic similarities documented in the literature 
across the study populations and design a unified nutritional intervention scheme. 
• Determine expected cerebral modifications resulting from the intervention by 
standardizing the protocol in neurotypical animal models. 
Goals: 
• 
Create a homogeneous information base documenting physiological and metabolic 
affinities among the target populations. 
• 
Obtain audiovisual records of families highlighting quality of life aspects. 
• 
Establish a specialized dataset on sleep habits of individuals with the studied 
neurodevelopmental disorders. 
• 
Document neuropsychological and behavioral profiles within family, social, and 
school contexts. 
Activities: 
• 
Bimonthly 1: Confirm study populations (Down Syndrome, ASD, ADD).  
• 
Assign dietary subgroups (Pilot, Diet, Control). 
• 
 Conduct studies of the T-2 investigational nutritional formulation 
• 
Baseline studies including laboratory tests, clinical reviews, anthropometric 
measures, 
ethnographic 
interviews, 
neuropsychological 
tests, 
full 
polysomnographic records, and P300 potentials.  

• 
Standardize animal model protocol. 
• 
Month 1: Start nutritional intervention (diet implementation). 
• 
Month 4-6: Report baseline results, documenting biomedical, dietary, familial, 
cognitive, behavioral, and sleep-related findings. Conduct behavioral tests in animal 
models. 
Expected Results at the End of Stage I (6 months): 
• 
Statistical report on physiological profiles, allergies, and food sensitivities. 
• 
Statistical report on sleep disorders and comorbidities. 
• 
Repository of family testimonies on quality of life. 
 
Stage II: Scientific Conclusions 
Duration: Second Semester 
Document 
and 
analyze 
biomedical, 
neuropsychological, 
sleep-physiology, 
and 
ethnographic outcomes across groups. 
Goals: 
• 
Validate or reject the hypothesis of cognitive and behavioral improvements following 
dietary intervention, contrasting supplemented versus non-supplemented groups. 
• 
Evaluate secondary hypotheses regarding ethnography and sleep physiology. 
Activities: 
• 
Conduct follow-up studies (laboratory tests, clinical reviews, anthropometric 
measures, ethnographic interviews, neuropsychological tests, polysomnography, 
P300 potentials). 
• 
Report comparative analyses between baseline and follow-up results. 
• 
Document biochemical, immunological, familial, social, and neuropsychological 
changes, as well as sleep physiology outcomes. 
Expected Results and Deliverables at the End of Stage II: 
• 
Technical reports on biochemical, anthropometric, and dietary allergy/sensitivity 
changes. 

• 
Technical reports on changes in quality of life within families and social circles. 
• 
Technical reports on sleep habit modifications. 
• 
Technical reports on cognitive and behavioral changes. 
 
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APPENDIX “A”: INFORMED CONSENT 
ETHICAL CONSIDERATIONS AND/OR INFORMED CONSENT FORM 
The principles of this informed consent process are grounded in the ethical foundations of 
the Declaration of Helsinki, the International Conference on Harmonization (ICH), Good 
Clinical Practice (GCP) guidelines, and all applicable regulatory requirements. 
For this study, written informed consent will be obtained prior to the initiation of any 
procedure or evaluation by the investigator or an authorized delegate, as documented on 
the Delegation of Responsibilities Sheet. 
Legal guardians of participants will be provided with both oral and written information 
regarding the nature and objectives of the study, as well as the procedures involved, before 
consent is obtained. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
INFORMED CONSENT TO PARTICIPATE IN A RESEARCH STUDY 
Protocol Title: Neuro-Nutrition as Support for Physiological Performance and Cognitive 
Skills in Individuals with Trisomy 21, Autism Spectrum Disorders, and Attention Deficit 
Disorder. 
CONACYT Project Number: __________________ 
Research Team: 
• 
Sleep Physiology Area Lead: Dr. Elizabeth Ibarra Coronado 
• 
Biomedical Area Lead: I.B. Cecilia Fernández Aguirre 
• 
Ethnographic Area Lead: Lic. Arturo Ramírez Ramos 
The study will be conducted at the following locations: 
• 
DOMUS Instituto de Autismo 
• 
Integración Down I.A.P. 
• 
Facultad de Psicología – Universidad Nacional Autónoma de México (UNAM) 
• 
Instituto Mexicano de Medicina Integral de Sueño 
• 
Participants’ homes 
Name of Participant: ___________________________________________ 
You and your child are invited to participate in this research study. Before making a decision, 
you should carefully read and understand each section of this document. This process is 
known as informed consent. Please feel free to ask any questions at any time to clarify any 
doubts you may have. 
If you agree for your child to take part in the study, you will be asked to sign this consent 
form. 
 
JUSTIFICATION OF THE STUDY 
Improvements in cognitive skills and overall quality of life have been documented in 
individuals with Down Syndrome (DS), Autism Spectrum Disorders (ASD), and Attention 
Deficit Disorders (ADD/ADHD) when dietary modifications eliminate gluten and casein and 

incorporate nutritional supplements. The objective of this project is to extend these benefits 
to a broader population with the same conditions. 
A maximum of 90 participants will be enrolled, each assigned to one of three groups (two 
dietary intervention groups and one control group) and monitored over the course of one 
year. 
Progress will be evaluated through a combination of traditional laboratory tests 
(hematology, blood chemistry, cortisol, homocysteine, C-reactive protein, stool analyses), 
cognitive and behavioral assessments, polysomnography, event-related potentials (P300), 
anthropometric measurements, and ethnographic interviews. Additionally, specialized 
analyses will be performed in the United States, including Organic Acid Profile, IgG Food 
Allergy and Sensitivity Tests, and Gluten/Casein Peptide Assays. 
 
OBJECTIVE OF THE STUDY 
The purpose of this study is to investigate behavioral and cognitive changes in individuals 
with Autism Spectrum Disorders (ASD), Attention Deficit Disorder (ADD/ADHD), or Down 
Syndrome (DS) through dietary modification. The intervention specifically involves 
eliminating harmful dietary components while incorporating nutrients that are typically 
under-metabolized due to the underlying characteristics of these conditions. 
BENEFITS OF THE STUDY 
The study aims to expand scientific knowledge on the role of nutrition in cognitive 
functioning among individuals with these conditions, with the goal of supporting therapeutic 
management and contributing to the improvement of quality of life. 
STUDY PROCEDURES 
If you consent for your child to participate, the following procedures will be performed: 
• 
Blood, urine, and stool tests. 
• 
Medical examinations by specialists. 
• 
Cognitive and behavioral assessments. 
• 
Ethnographic interviews and questionnaires. 
• 
Polysomnographic sleep studies to evaluate sleep physiology. 
These procedures are non-invasive and will not cause pain. 

 
RISKS ASSOCIATED WITH THE STUDY 
No significant risks are expected from the procedures mentioned. 
 
CLARIFICATIONS 
• 
Participation is voluntary. 
• 
All dietary guidelines, supplement intake, and dosage instructions must be followed 
precisely. 
• 
Parents are required to attend support sessions throughout the research period. 
• 
Declining participation will not result in any negative consequences. 
• 
You may withdraw your child at any time without penalty by informing the research 
team. 
• 
There will be no cost to you for the tests or procedures required for this study. 
• 
No financial compensation will be provided for participation. 
• 
Confidentiality of personal and medical information will be strictly maintained. 
• 
If participation requirements (dietary compliance, supplement intake) are not met, 
the research team may ask you to withdraw without prejudice. 
• 
Periodic progress reports will be provided to participating families during the study. 
If you agree to participate, you formally commit to complying with the nutritional 
instructions provided, as these are essential for the accuracy and validity of the study 
results. 
 
INFORMED CONSENT FORM 
I, ____________________________________, have read and understood the information 
above, and my questions have been answered satisfactorily. I understand that study data 
may be used for scientific purposes. I consent to participate in this research study. 
Parent/Guardian Signature: ______________________ Date: _____________ 
Witness: ______________________ Date: _____________ 

Witness: ______________________ Date: _____________ 
Investigator’s Statement: 
I have explained to Mr./Ms. ____________________ the nature and purpose of the research, 
the risks and benefits of participation, and answered questions to the best of my ability. I 
certify that I am familiar with applicable ethical standards for research involving human 
participants. 
Investigator’s Signature: ______________________ Date: _____________ 
 
CONSENT WITHDRAWAL FORM 
Protocol Title: Neuro-Nutrition Phase II as Support for Physiological Performance and 
Cognitive Skills in Individuals with Trisomy 21, Autism Spectrum Disorders, and Attention 
Deficit Disorder. 
Study Sites 
The study will be conducted at the following locations: 
• 
DOMUS Instituto de Autismo 
• 
Facultad de Psicología – Universidad Nacional Autónoma de México (UNAM) 
• 
Instituto Mexicano de Medicina Integral de Sueño 
• 
Participants’ homes 
Participant’s Name: ___________________________________________ 
I hereby inform you of my voluntary decision to withdraw from this research protocol for 
the following reasons: 
 
Upon this withdrawal, no further study information or documents will be provided, and I 
commit to returning any unused formulation to the principal investigator. 
Parent/Guardian Signature: ______________________ Date: _____________ 
Witness: ______________________ Date: _____________ 
Witness: ______________________ Date: _____________