clinical clues in pediatric functional medicine...• functional medicine • homeopathy •...

CLINICAL CLUES IN PEDIATRIC FUNCTIONAL MEDICINE

Elisa H. Song, MDSeptember 2019

WHO I AM

WHO I AM

The 2 things I’m most proud of:• Mom to 2 awesome kids! • Integrative pediatrician in

the SF Bay Area

@2019 Elisa Song, MD - Healthy Kids Happy Kids

WHO I AM

• Stanford undergrad in political science/public policy • NYU School of Medicine • UCSF Pediatric Residency• Additional training in:

• Functional Medicine• Homeopathy• Traditional Chinese Medicine (acupuncture and herbs)• Western herbs, homotoxicology, essential oils, acupressure, infant

massage, clinical hypnosis (SDBP)• Lecturer for: CEDH, Academy for Pain Research, Center for Advanced

Acupuncture Pediatrics, IFM, Holistic Pediatric Association• Started Whole Child Wellness, an integrative pediatric practice in

December 2005, now Whole Family Wellness• Started Healthy Kids Happy Kids in June 2016, an online holistic

pediatric and pediatric functional medicine resource for parents!• Host of Thriving Child Summit 2016 and 2017


www.wholefamilywellness.org

www.healthykidshappykids.com

www.thrivingchildsummit.com @2019 Elisa Song, MD - Healthy Kids Happy Kids

By 2025 it is expected that vast majority of children in the US will have a chronic condition

Ref: Bethel, Christina D. A National and State Profile of Leading Health Problems and Health Care Quality for U.S. Children. Academic Pediatrics, 2011. Estimate of future impact is conservative given historical growth rates

0%10%20%30%40%50%60%70%80%90%

1960 2007 2015 2025

% of Children in US with Diagnosed Chronic Conditionprojected

OUR KIDS ARE SICK,AND GETTING SICKER…

@2019 Elisa Song, MD - Healthy Kids Happy Kids © Beth Lambert, Documenting Hope

our kids are sick

*Ref: Bethel, Christina D. A National and State Profile of Leading Health Problems and Health Care Quality for U.S. Children. Academic Pediatrics, 2011.

• Asthma• Allergies• ADHD/ADD• SPD• Autism• Crohn’s • Colitis• PANDAS/PANS• Depression• Bipolar Disorder• Autoimmunity• Obesity• Diabetes• . . .

THE “NEW NORMAL”

© Beth Lambert, Documenting Hope@2019 Elisa Song, MD - Healthy Kids Happy Kids

NOT SO NORMAL…• Many chronic health problems are on the rise in children

• Childhood cancer• Autoimmune illnesses• Endocrine disorders• Reproductive system disorders• Neurodevelopmental disorders

• In 2018, 1 in 59 children (1 in 34 in New Jersey) dx’ed as having autism spectrum disorder

• Neuro-psychiatric disorders• PANDAS/PANS

• NEJM (2005) “A Potential Decline in Life Expectancy in the US in the 21st

Century”• There has been a slow steady increase in life expectancy over past thousand

years• Because of lifestyle changes and the rise in childhood obesity with resultant

health problems, this could be the first time that children today live less healthy and have shorter lifespans than their parents!!!


WHY?


MAJOR INFLUENCES ON CHILDREN’S HEALTH IN THE 21ST CENTURY

• Overconsumption & undernutrition• Deficient immunologic education (excessive hygiene) • Overuse of antibiotics, antacid medications, mood regulators & other

pharmaceuticals• Environmental toxicity (xenobiotics)• Psychological stress

Maladaptive epigenetic programming…


THE STANDARD AMERICAN DIET...

I’ll have fries with that...

And don’t forget the Diet Coke!


WHAT CAN WE DO?


FUNCTIONAL MEDICINE & KIDS

• Functional medicine offers a broad, systems-based context in which environmental inputs can be understood as one of many potential triggers that interact with other lifestyle factors and genetic antecedents to produce chronic dysfunction & disease.

• NOW is the time to act!


WHAT IS FUNCTIONAL MEDICINE?

Functional medicine is anchored by an examination of the core clinical imbalances that underlie various disease conditions. Those imbalances arise as environmental inputs such as diet, nutrients (including air and water), exercise, and trauma are processed by one’s body, mind, and spirit through a unique set of genetic predispositions, attitudes, and beliefs.

www.functionalmedicine.org


http://www.functionalmedicine.org/

MY APPROACH WITH KIDS• The child is your client• Children can respond amazingly quickly• Start LOW and go SLOW• Start with the KEY imbalances, and the rest often falls into place• Ask parents and children how they would like to proceed• Close follow-up is very important• Be POSITIVE

• Be the CHEERLEADER for child and parents


TIPS TO GET KIDS TO TAKE SUPPLEMENTS

• Don’t insert your ideas about how “good” or “bad” it tastes• Start slowly, with bland-tasting ones first

• i.e. probiotics before zinc or glutathione• Don’t lie about what you’re doing• Don’t put into their favorite food or drink• Be consistent and firm• Use positive reinforcement• Kids can learn to swallow pills

• Oraflo cup• OT support• Online videos

• Syringes can be lifesavers!• Deliver supplements between back gum and cheek to avoid tastebuds

on front of tongue where they’re more concentrated• Put liquids in a covered container to hide the smell and color

• We taste with our eyes and nose, not just our tongue!@2019 Elisa Song, MD - Healthy Kids Happy Kids

• Smoothies • Give with a small amount of smoothie first, then drink the rest

unadulterated• Tart, dark juice

• Pomegranate, blueberry, etc.• Masks the flavor and color

• Frozen grape juice concentrate• Add stevia, xylitol, maple syrup, honey, chocolate syrup• Jello smoothie shots• Supplement gummies• Ice cube popsicles• Giant chocolate chip (Enjoy Life brand)• Baked into something, if heat resistant (check label)

• Most minerals and amino acids are OK• Never probiotics or EFAs

• In peanut or other nut/seed butter• If bitter, mix with a savory food

TIPS TO GET KIDS TO TAKE SUPPLEMENTS


WHAT DOSAGE FOR KIDS?

@2019 Elisa Song, MD - Healthy Kids Happy Kids https://www.fxmedicine.com.au/blog-post/determining-dosages-children

https://www.fxmedicine.com.au/blog-post/determining-dosages-children

CORE CLINICAL IMBALANCESIN CHILDREN


ASSIMILATION(DIGESTION, ABSORPTION, MICROBIOTA/GI)


MALDIGESTION/MALABSORPTION – CLINCAL SIGNS & SYMPTOMS

• Gas and bloating• Burping • Abdominal pain with or after

meals• Vomiting • Sensation of fullness after a few

bites• Weight loss/Failure to thrive• Fatigue• Diarrhea• Signs of nutrient deficiencies (to

follow…)


• Fat malabsorption• Greasy, floating stools, whiny

film in toilet water • Carbohydrate malabsorption

• Foamy, green, cramping diarrhea

• BF infant too much foremilk?• Protein malabsorption

• Edema (especially belly, ankles/feet)

• Muscle weakness/wasting• Fatigue• Diarrhea

TESTING FOR MALDIGESTION/MALABSORPTION

• Pancreatic elastase (ideal >500)• Serum amylase/lipase• Qualitative fecal fat• Stool reducing substances• Prealbumin – marker for protein malabsorption and general nutritional status• RBC zinc• RBC magnesium• Complete blood count (hemoglobin, MCV)• Ferritin, Iron/IBC• Fat soluble vitamins (Vitamins ADEK)• Vitamin B12, folate• Celiac markers (anti-TTG IgG/IgA, anti-gliadin IgG/IgA)• Comprehensive stool analysis for dysbiosis


THE MOST COMMON PEDIATRIC NUTRIENT DEFICIENCIES

• Zinc• Magnesium• Iron• Vitamin D


ZINC DEFICIENCY IN CHILDREN


WHAT ZINC DOES• Essential trace mineral• Zinc intake closely tied with protein intake• Cofactor for 100+ enzymes systems – carbonic anhydrase, alkaline phosphatases,

dehydrogenases, carboxypeptidases• Involved in growth and tissue repair (skin, gut lining, etc.)• Affects normal growth and development• Involved in taste, smell, and appetite regulation• Maintains healthy brain function• Involved in immune function and response to infection• Inhibits histamine release in human basophils and mast cells• Influences NMDA and GABA receptors

• Deficiency associated with anxiety, OCD, and panic disorders• Plays a role in synthesizing testicular hormones


SIGNS OF ZINC DEFICIENCY –HISTORY

• Frequent infections• Picky eating• Low appetite• Impaired taste and smell• Pica • Failure to thrive• Auditory processing/sensitivity• Tactile sensitivity• Diaper rash that doesn’t heal• Eczema that doesn’t heal• Poor wound healing

• Thin hair, alopecia• Food sensitivities/Increased intestinal

permeability• Chronic diarrhea• Attention/focus issues• Irritability• Anxiety/OCD• Depression• Histamine symptoms• Primary hypogonadism (boys)


ZINC & PICKY EATERS• Affects sense of taste/smell and appetite PICKY EATERS

• Zinc supplementation directly stimulates appetite and food intake via vagus nerve and neuropeptides in hypothalamus

• Challenge of assessing who is zinc deficient

• Plasma zinc bound to albumin, may not be accurate

• RBC zinc is more relevant• Cu:Zn ratio may be an important marker

for zinc deficiency esp in taste disorders• Cu/Zn of 1.1 found to be the threshold

level for detecting taste disorders associated with zinc deficiency


ZINC & THE GUT

• Zinc is required for healthy intestinal barrier integrity

• Zinc supplementation can help resolve increased intestinal permeability (“leaky gut”)


ZINC & THE BRAIN• Low maternal zinc status may increase risk for ASD in offspring by affecting

the developing gut-brain connection• Zinc is necessary for heathy fetal gut development and intestinal lining integrity• Zinc involved in regulation of neurogenesis, neuronal migration and

differentiation• Neonatal zinc deficiency may be associated with increased risk for autism• Low zinc may be associated with ADHD sx

@2019 Elisa Song, MD - Healthy Kids Happy Kidshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4386645/

https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=4386645_NP2015-972791.002.jpg

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4386645/

ZINC & AUDITORY PROCESSING

• Zinc involved in neuronal synapses in region of neocortex that processes sound “gain modulation” in the auditory cortex

• Gain modulation when an input to a neuron alters the relationship between the intensity of the stimulus (i.e., loudness of sound) and strength of the neuron’s response to that stimulus

• Binding zinc at synapses before it can act ENHANCED neuronal response to loud sounds


SIGNS OF ZINC DEFICIENCY –PHYSICAL EXAM

• Low weight/height velocity• Persistent diaper rash

• Use Zinc oxide diaper cream• Severe consider Acrodermatitis

enteropathica (AE) – inborn error of zinc metabolism

• Eczema, dry skin• Poor wound healing• Beau’s lines on nails

• Also due to trauma, cold exposure• Thin hair


Image credit: www.healthline.com

http://www.healthline.com/

DIAGNOSING ZINC DEFICIENCY• RBC zinc• Plasma zinc/Serum copper• Prealbumin (marker for adequate protein intake)

• Reference ranges:• Infants: • <5 days old: 6 to 21 mg/dL• 6 days – 12 months: not established• Children:• Ages 1 to 5: 14 to 30 mg/dL• Ages 6 to 9: 15 to 33 mg/dL• Ages 10 to 13: 22 to 36 mg/dL• Ages 14 to 19: 22 to 45 mg/dL

• Alkaline phosphatase• Indirect marker for zinc depletion (zinc cofactor for alkaline phosphatase activity)


RECOMMENDED DAILY INTAKE OF ZINC


Table 1: Recommended Dietary Allowances (RDAs) for Zinc [2]Age Male Female Pregnancy Lactation0–6 months 2 mg* 2 mg*7–12 months 3 mg 3 mg1–3 years 3 mg 3 mg4–8 years 5 mg 5 mg9–13 years 8 mg 8 mg14–18 years 11 mg 9 mg 12 mg 13 mg19+ years 11 mg 8 mg 11 mg 12 mg

https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/


WAYS TO SUPPORT HEALTHY ZINC LEVELS

• Introduce organic meats as baby’s first foods• Focus on zinc-rich foods• Supplementation often needed

• Zinc picolinate* (best absorption), zinc citrate, zinc gluconate• Typical dose – 1-2 mg/kg/day of elemental zinc• Simultaneous iron supplementation may decrease zinc absorption • Watch for serum copper imbalance with long-term supplementation

• Zinc inhibits intestinal absorption of copper• Otherwise very low toxicity risk even at 10x recommended RDI• Most common side effect – nausea/vomiting


TOP ZINC-RICH FOODS

• Pumpkin seeds• Beans• Grassfed Beef • Lamb • Sesame seeds• Garbanzo beans• Lentils• Cashews• Quinoa • Eggs

• Organic poultry• Shellfish• Raw sprouts• Liver• Spinach• Watermelon seeds • Garlic• Peanuts • (Dairy products)


MAGNESIUM DEFICIENCY IN CHILDREN


WHAT MAGNESIUM DOES

• Needed for over 300 biochemical reactions in the body• 50-60% of body’s magnesium is stored in the bones• Involved in regulation of calcium and potassium• Regulates smooth muscle relaxation

• Implicated in constipation and asthma• Helps regulate blood sugar and insulin sensitivity• Implicated in migraine headaches• Natural N-methyl-D-aspartic acid (NMDA) antagonist and GABA agonist

• Supports healthy mood, focus, and sleep


SIGNS OF MG DEFICIENCY –HISTORY

• Constipation • Asthma• Anxiety• Sleep disturbances• Headaches • Muscle cramps and weakness• Fatigue• Seizures • Cardiac arrhythmias


SIGNS OF MG DEFICIENCY –PHYSICAL EXAM

• Nothing in particular…


DIAGNOSING MG DEFICIENCY• RBC magnesium• Serum magnesium• Consider testing for associated abnormalities

• Low calcium• Low Vitamin D• Low potassium• Fasting glucose, insulin, hemoglobin A1c


RECOMMENDED DAILY INTAKE OF MAGNESIUM

Table 1: Recommended Dietary Allowances (RDAs) for Magnesium [1]Age Male Female Pregnancy LactationBirth to 6 months 30 mg* 30 mg*7–12 months 75 mg* 75 mg*1–3 years 80 mg 80 mg4–8 years 130 mg 130 mg9–13 years 240 mg 240 mg14–18 years 410 mg 360 mg 400 mg 360 mg19–30 years 400 mg 310 mg 350 mg 310 mg31–50 years 420 mg 320 mg 360 mg 320 mg51+ years 420 mg 320 mg


WAYS TO SUPPORT HEALTHY MAGNESIUM LEVELS

• Focus on magnesium-rich foods• Epsom salt baths• Magnesium chloride oil• Supplement often needed

• Typical dose – ???• Magnesium glycinate* – calming, helps sleep, less laxative• Magnesium citrate – more laxative, calming, helps sleep• Magnesium threonate – crosses BBB, support focus and learning• Magnesium malate – malic acid supports mitochondria, energizing• Magnesium oxide – most laxative, poor absorption


TOP MG-RICH FOODS

• Pumpkin seeds• Dark chocolate!• Spinach• Swiss chard• Soybeans• Sesame seeds• Black beans• Quinoa• Cashews• Sunflower seeds• Beet greens • Bananas

• Avocado • Navy beans• Buckwheat • Pinto beans• Brown rice• Lima beans• Millet• Oats • Almonds • Papayas• Flaxseeds


IRON DEFICIENCY IN CHILDREN


WHAT IRON DOES• An essential component of hemoglobin – oxygen-carrying compound• Heme iron is found in meat, poultry, and fish

• Good absorption, unaffected by iron status• Non-heme iron is found in fruits, vegetables and iron-fortified foods

• Absorption increases as iron status declines• “Free” iron is not good – can cycle between Fe(2+) and Fe(3+) and produce

potentially toxic free radicals• 20-30% of total body iron is in storage protein ferritin and hemosiderin• Critical cofactor for gluconeogenesis and DNA/RNA synthesis• Required for normal myelination


SIGNS OF IRON DEFICIENCY –HISTORY

• Most common nutritional deficiency in children

• Microcytic hypochromic anemia• Weakness, fatigue• Cold intolerance• Developmental delays in infants

(irreversible)• Poor feeding• Pica

• Pagophagia – craving for ice• Clay, dirt, rocks, starch, chalk, soap,

paper, cardboard, raw rice


• Poor cognitive achievement in school• Lower scores in cognitive testing,

memory, reading, verbal, and math• Poor concentration/focus/attention

(“ADD/ADHD”)• Slower visual and auditory processing• Irritability, mood changes• Breathholding spells• Restless legs and periodic limb

movement disorder• Febrile seizures• ?increased risk for infection

SIGNS OF IRON DEFICIENCY –HISTORY

• High cow’s milk consumption• Vegetarian/vegan diet

• Heme (animal sources or iron) higher bioavailability than non-heme sources (fruits, vegetables, grains, iron-fortified foods)

• Bleeding • Rectal bleeding• Frequent nosebleeds• Heavy menstrual periods


SIGNS OF IRON DEFICIENCY –PHYSICAL EXAM

• Pale skin• Pale sclera• Pale buccal mucosa• Dark circles under the eyes• Nail changes – koilonychia (“spoon nails”)• Glossitis• Angular cheilitis/stomatitis


KOILONYCHIA (“SPOON NAIL”)• Iron-deficiency• Hemochromatosis

(too much iron)• Raynaud’s disease• Hypothyroidism• Heart disease• Onychomycosis• Nail trauma

• Vitamin B deficiency• Celiac disease• Diabetes• Psoriasis• Lupus• Malnutrition


Image credit: www.gponline.com

http://www.gponline.com/

ANGULAR CHEILITIS

• Common causes• Yeast infection***• B-vitamin deficiency (all of them)• Staph/Strep infection• Iron deficiency• Zinc deficiency

• Treatment • Topical antifungal• Topical antibiotic• Zinc supplementation if indicated• Iron supplementation if indicated• Methylated B-complex if indicated


Photo credit: Karan Bunjean/Shutterstock.com

DIAGNOSING FE DEFICIENCY• AAP recommends universal screening for iron-deficiency anemia at 12 mos

• Nadir of iron stores is 9 months• Complete blood count – assess hemoglobin and MCV (microcytosis)• Hemoglobin (Anemia as defined by WHO):

• Children 6 months to <5 years: 11 g/dL• •Children 5 to <12 years: 11.5 g/dL• •Children 12 to <15 years: 12 g/dL• •Non-pregnant women: 12 g/dL• •Pregnant women: 11 g/dL• •Men ≥15 years: 13 g/dL

• Ferritin• Iron deficiency anemia – above +:

• Ferritin <12 micrograms/L for children 6 months to <5 years• Ferritin < 15 micrograms/L for children 5 to <12 years

• Caution – ferritin is an acute phase reactant• If pica and/or iron-deficiency anemia check blood lead levels

• Significant correlation between lead poisoning and IDA @2019 Elisa Song, MD - Healthy Kids Happy Kids

RECOMMENDED DAILY INTAKE OF IRON

• Optimal ferritin >40-50 micrograms/L• Infants

• Full-term – 1 mg/kg daily (maximum 15 mg)• Premature – 2 to 4 mg/kg daily (maximum 15 mg)• Breast milk contains only 0.3 to 1.0 mg/L iron, but has high bioavailability (50

percent)• Iron-containing formulas typically have 12 mg/L iron, but low bioavailability (4 to

6 percent)• Children

• 1 to 3 years old – 7 mg daily• 4 to 8 years old – 10 mg daily• 9 to 13 years old – 8 mg daily

• Adolescents 14 to 18 years• Boys – 11 mg daily• Girls – 15 mg daily


WAYS TO SUPPORT HEALTHY IRON LEVELS

• Focus on iron-rich foods• Shaved frozen liver in soups, smoothies, stir-fries,

oatmeal, etc.• Get in those green leafy veggies!

• Cook in cast iron skillet• Supplementation may be needed

• Floradix Iron + Herbs• Ferrous bisglycinate (“gentle iron)” has lower GI

side effects vs. ferrous sulfate• Most common complaint – abdominal pain,

constipation• Watch for teeth staining


TOP FE-RICH FOODS• Pumpkin seeds• Dark chocolate• Liver and organ

meats• Lentils• Grass-fed beef• Blackstrap

molasses• Swiss chard• Spinach• Cumin• Parsley • Turmeric • Beet greens• Collard greens

• Bok choy• Asparagus • Leeks• Soybeans• Sesame seeds• Chickpeas• Lima beans• Olives• Navy, kidney,

black, pinto• Brussel sprouts• Beets• Kale• Broccoli


VITAMIN D DEFICIENCY IN CHILDREN


WHAT VITAMIN D DOES• Fat-soluble vitamin – actually a HORMONE precursor to steroids hormones• Vitamin D from sun, food and supplements activated with 2 hydroxylations

• Liver converts Vitamin D 25-hydroxyvitamin D (calcidiol)• Kidney converts 25(OH)D 1,25-dihydroxyvitamin D (calcitriol)

• Physiologically active form of Vitamin D• Promotes calcium absorption in the gut• Regulates serum calcium/phosphate• Enables normal bone mineralization• Modulates cellular proliferation, differentiation and apoptosis• Regulates immune function• Reduces inflammation• Affects brain function and development• Modulates neurotransmitter release


SIGNS OF VIT D DEFICIENCY –HISTORY

• Exclusively breastfed (in Vitamin D-deficient mama!)

• Frequent illnesses• Food allergies• Atopy – eczema, asthma• Dental caries • ADHD, attention, focus• Anxiety, depression, OCD• Irritable bowel symptoms• Easy or frequent fractures• Rickets in severe cases

• Autoimmune disease (PANDAS, SLE, juvenile dermatomyositis, alopecia areata, juvenile idiopathic arthritis, vitiligo, Type 1 diabetes)

• Medications• Glucocorticoids

• How many children are on glucocorticoids for eczema, asthma, allergic rhinitis?

• YES topical, inhaled and intranasal glucocorticoids COUNT

• Ketoconazole and other antifungals• Antiepileptic drugs• Antiretroviral drugs


SIGNS OF VIT D DEFICIENCY –PHYSICAL EXAM

• No specific physical exam findings (unless obvious rickets)…


DIAGNOSING VITAMIN D DEFICIENCY

• Measure serum 25-hydroxyvitamin D• 25(OH)D is the main circulating form of Vitamin D• Half-life of 2-3 weeks• 1,25-dihydroxyvitamin D has half-life of ~4 hours and may fluctuate due to PTH

influence in response to changes in calcium levels


OPTIMAL VITAMIN D LEVELS?• AAP goal: maintain 25(OH)D at > 20ng/ML (50 nmol/L)• 2016 Global Consensus recommendations (based on risk for rickets)

• Vitamin D sufficiency: 20 to 100 ng/mL (50 to 250 nmol/L)• Vitamin D insufficiency: 12 to 20 ng/mL (30 to 50 nmol/L)• Vitamin D deficiency: <12 ng/mL (<30 nmol/L)

• Vitamin D Council recommends maintaining serum levels 50 ng/ml (125 nmol/L)

• Deficient: 0-40 ng/ml (0-100 nmol/l)• Sufficient: 40-80 ng/ml (100-200 nmol/l)• High Normal: 80-100 ng/ml (200-250 nmol/l)• Undesirable: > 100 ng/ml (> 250 nmol/l)• Toxic: > 150 ng/ml (> 375 nmol/l)


RECOMMENDED DAILY INTAKE OF VIT D

• AAP recommendations• Breastfed infants – Vitamin D3 400 IU (10mcg) daily• Children 1-18 years – Vitamin D3 600 IU (15mcg) daily

• IOM recommendations• 0-12 months 400IU daily• 1-70 years 600IU daily (even pregnant and lactating)• >70 years 800IU daily• “ It is still not possible to specify a relationship between vitamin D and health

outcomes other than bone health.” • Higher doses recommended for those at risk:

• Darker-skinned patients, • Winter months at higher latitudes• Patients on glucocorticoids, antiepileptic meds, ketoconazole and HIV meds

• Vitamin D toxicity anorexia, weight loss, polyuria, arrhythmias


VITAMIN D COUNCIL RECOMMENDATIONS

• Vitamin D Council recommended daily MAINTENANCE dose:• Children: Vitamin D3 1000IU per 25 pounds of body weight up to 125 pounds• Adults: 5000IU (including pregnant and BF mothers) with upper limit 10,000IU/day

• If pregnant/nursing CHECK LEVELS! If mother’s levels are optimal, then nursing baby does not need supplementation)

• If >10,000IU/day, check 25(OH)D levels q3months


VITAMIN D SOURCES• Best source: SUNLIGHT

• 10-15 min/day near midday• (may not be adequate if darker

skin, sunblock, northern latitudes in winter)

• Very few food sources• Cod liver oil• Sardines, salmon, mackerel, other

fatty fish• Cow’s milk and Dairy products

• If you’re not sensitive• Avoid when sick

• Eggs• Caviar• Mushrooms

Supplementation usually needed@2019 Elisa Song, MD - Healthy Kids Happy Kids

GUT DYSBIOSIS IN CHILDREN


BACTERIAL GUT DYSBIOSIS –HISTORY

• Mood and behavior problems• Infant cognitive development and temperament concerns• Autism

• Clostridia and propionic acid in autism• ADHD• Atopy – eczema, asthma, allergic rhinitis• Autoimmune disease risk increased with bacterial dysbiosis

• Citrobacter spp, Klebsiella spp, Proteus spp• Strep infections – pharyngitis, impetigo, perianal/perivaginal strep, PANDAS• IBS symptoms – bloating, gas, abdominal pain• GERD


BACTERIAL GUT DYSBIOSIS –DIAGNOSIS & TREATMENT

• Comprehensive stool analysis• Stool culture• Stool PCR analysis

• Throat, nose, skin and perianal swabs for culture (if indicated)

• Treatment• Appropriate pharmaceutical and herbal antimicrobials• Support gut eubiosis probiotics, prebiotics, glutamine, phytonutrient-rich diet• Inulin/FOS/GOS feed clostridia, Citrobacter, klebsiella, proteus and candida


YEAST GUT DYSBIOSIS –HISTORY

• Antibiotic use (ever, even in utero)• Corticosteroid use• Oral thrush• Yeast diaper rash• Athlete’s foot (tinea pedis)• Jock itch (tinea cruris)• Ringworm (tinea corporis)• Toenail fungus (onychomycosis)• Tinea capitis• Chronic congestion (fungal sinus infection)• Fatigue


YEAST GUT DYSBIOSIS –HISTORY

• Sugar cravings• Yeast ferment sugar to ALCOHOL

• Sugar = processed sugar, grains, fruit• Acetaldehyde formed as a byproduct of ethanol oxidation• Acetaldehyde is TOXIC and must be broken rapidly down by aldehyde

dehydrogenase• Toxic effects seen in autism, alcoholism, diabetes, neurodegenerative ds, cancer…• Xylitol can inhibit carcinogenic acetaldehyde production by Candida spp!

• Intermittent “Drunk” behavior, esp after sugar consumption• Think of all the ways you’ve seen someone act when drunk:

• Happy and overly “goofy” and giddy, inappropriate laughter• Confused, spacy, “out-of-it”, “brain fog”• Angry, mean, out-of-control tantrums• Sad, weepy, depressed


YEAST GUT DYSBIOSIS –PHYSICAL EXAM

• White coating on tongue• Fungal skin and nail

infections• Yeast diaper rash• Athlete’s foot (tinea pedis)• Jock itch (tinea cruris)• Ringworm (tinea corporis)• Toenail fungus

(onychomycosis)• Tinea capitis


YEAST DYSBIOSIS – DIAGNOSIS

• Clinical history…• Comprehensive stool analysis• Urine organic acids

• Arabinose – also found in fruits (apples, plums, cherries, grapes)• Citramalic acid – also found with clostridia• Tartaric acid – also found in grapes, cherries, aloe vera, tamarind

• Nasal swab for fungal culture (if indicated)


YEAST DYSBIOSIS – TREATMENT

• Herbal and pharmaceutical antifungal treatments as indicated

• Biofilm protocol likely necessary• Probiotics• Reduce sugars• Fermented foods?


PARASITE GUT DYSBIOSIS –HISTORY

• Teeth grinding• Pica • Mouthing behavior• Anal pruritis• Dark circles under eyes• Behavioral problems/

Tantrums/sensory issues• Tics • Sleep disturbance• Abdominal pain

• Bloating/gas• Nausea, vomiting, diarrhea• Quick satiety• Fatigue• Weight loss• Seizures

• FLARES AROUND THE FULL MOON


PARASITE GUT DYSBIOSIS –DIAGNOSIS & TREATMENT

Diagnosis:• Clinical history – have a high index of suspicion…• Stool ova & parasite testing – many flaws• Parasite PCR testing – just passersby?

Treatment:• Typically combo pharmaceutical + herbal

• Nitazoxanide ($$$) more palatable than metronidazole • Many antiparasitic herbs are very bitter

• Black walnut, wormwood (artemisia), cloves, berberine, thyme, pumpkin seeds• Pulse treatments 3-4 days before and after full moon x 3-4 moon cycles


FOOD REACTIONS & CHILDREN


ADVERSE REACTIONS TO FOODS

• Allergy• IgE-mediated

• Hypersensitivity or delayed reaction• Mixed immunological• IgG, IgM, IgA, T-cells, other?

• Intolerance• Metabolic (chronic)

• i.e., lactase deficiency• Toxic spoilage, toxins (episodic)

• Other…


FOOD ALLERGIES• IgE-mediated reaction to protein

histamine hives, wheezing, diarrhea, life-threatening anaphylaxis

• Immediate reaction, within hours• May be lifelong• Diagnosis: Skin test, IgE bloodtest• More than 40% of those who develop

food allergy will become allergic to MORE than one food

• Increasingly common…• 65% of children with food allergy did

NOT have a parent with food allergy• WHY???


ANTIBIOTICS, ANTACIDS & ALLERGIES

• Almost 800,000 children over a 4-year period given antibiotics and antacids during first 6 months of life

• Increased risk for EVERY SINGLE ALLERGIC DISEASE• Food allergy, anaphylaxis, asthma, atopic dermatitis (eczema), allergic rhinitis,

allergic conjunctivitis, urticaria (hives), and contact dermatitis• Atopic disease AUTOIMMUNE PHENOMENA

• MORE THAN HALF of all children developed allergic disease during this 4 year period

• Dr. Edward Mitre:• “Gut bacteria play a role in a healthy immune system. Antibiotics and antacids

might change the makeup of a baby’s microbiome, perhaps enough to cause an overreaction in the immune system that shows up as an allergy.“


PREVENTING FOOD ALLERGIES• Diversity in diet during first year of life is KEY

• No more avoidance of allergenic foods <12 months of age• Increased dietary diversity during first year of life associated with lower risk of

developing food allergies• Decreased dietary diversity during first 12 months of life associated with

increased risk of asthma and allergic rhinitis• Avoidance of allergenic foods may increase risk of developing allergy to

THAT food• In 640 high-risk infants 4-11 months with severe eczema and/or egg allergy

• Peanut consumption group 1.9% developed peanut allergy• Peanut avoidance group 13.7% developed peanut allergy

• Introducing common allergenic foods (peanut, cooked egg, cow’s milk, sesame, whitefish, wheat) at 4-6 months of age (vs. waiting until 6 mos) significantly reduced development of food allergy


FOOD SENSITIVITIES• Non-IgE reaction, not necessarily to protein

• Natural or synthetic chemicals, dyes, additives• IgG- or IgA- mediated• Inflammatory response• Other immune response

• Delayed reaction, up to 48-72 hours• Can cause a huge range of symptoms• Very common – >up to 25-50% of population• Food sensitivities can develop to ANY food• Sign of a “leaky gut”• Can be resolved with the 5R’s@2019 Elisa Song, MD - Healthy Kids Happy Kids

DIAGNOSING FOOD SENSITIVITIES

• Elimination diet is the gold standard• Bloodtesting?

• IgG/IgA antibody testing• IgG4 food-specific antibodies are considered “protective” from IgE

antibodies to those foods• Leukocyte activation testing• Mediator Release Test


LEAKY GUT & PEDIATRIC DISEASE

Z Liu, N Li, J Neu (2005). Tight junctions, leaky intestines, and pediatric diseases; Acta Paediatrica 94 (4), 386–393.@2019 Elisa Song, MD - Healthy Kids Happy Kids

PEDIATRIC SYMPTOMS ASSOCIATED WITH LEAKY GUT

• Anxiety• Behavioral problems• Brain fog• Cognitive/memory deficits• Depression• Fatigue• Focus and attention problems• GI symptoms• Hyperactivity

• Chronic mucous congestion• Pruritis/hives• Dermatitis/rashes• Wheezing • Sleep disturbance


PEDIATRIC DISEASES ASSOCIATED WITH LEAKY GUT

• ADD/ADHD• Autism• Autoimmune disease• Behavioral problems• Recurrent ear infections• Frequent infections• Chronic abdominal pain• Chronic constipation• Toddler’s diarrhea

• GERD• Asthma• Eczema• Allergic rhinitis• Headaches• Anxiety/depression/mood disorders• Sensory processing disorder• Sleep disturbance/OSA• Urticaria


THE 5R PROGRAM TO HEAL YOUR CHILD’S GUT

• Remove – anything toxic/inflammatory to the gut• Food allergies/sensitivities/intolerances, food additives, medications, pathogens,

glyphosate, heavy metals, medications, mold, environmental toxins, EMFs, STRESS!• Endotoxins serum-derived bovine IgG

• Replace – whatever the gut is missing• Digestive enzymes, +/- HCl, CHEW!

• Reinoculate – with the good bugs• Probiotics, including psychobiotics• Prebiotics• Fermented foods (if histamine is not an issue)

• Repair – the gut lining• Gut Mucosal Integrity Nutrients – glutamine, fish oil, zinc, quercetin

• Rebalance – Restore the gut-mind-body-spirit connection• Sleep, exercise, stress reduction/mindfulness, time in nature


THE 5 R’S IN A NUTSHELL

• Free infographic on the 5 R’s to Healing Your Child’s Gut• http://healthykidshappykids.com/leaky-gut-guide/


http://healthykidshappykids.com/leaky-gut-guide/

THE DILEMMA IN TREATING FOOD ALLERGIES VS. SENSITIVITIES

To eat or not to eat, that is the question…


ARE YOU REACTING TO THE FOOD, OR WHAT’S IN IT?

• Basic components of “the food”• Natural processes – aging, insects (worms), fungi (grapes, tomatoes),

fermentation/mold (aspergillus – i.e., chocolate, malt, tea, citric acid)• Protectants (i.e., pesticides)• Spoilage (i.e., bacterial, fungal)• Genetic engineering• Processing – treatment

• Canning, freezing, heating, salting, smoking• Additives (MANY!)

• Preservatives (i.e., citric acid), antibiotics, hormones, enzymes (most of aspergillus)


WHAT IS THIS?“amyl acetate, amyl butyrate, amyl valerate, anethol, anisyl formate, benzyl acetate, benzyl isobutyrate, butyric acid, cinnamyl isobutyrate, cinnamyl valerate, cognac essential oil, diacetyl, dipropyl ketone, ethyl butyrate, ethyl cinnamate, ethyl heptanoate, ethyl heptylate, ethyl lactate, ethyl methylphenylglycidate, ethyl nitrate, ethyl propionate, ethyl valerate, heliotropin, hydroxyphrenyl- 2-butanone (10% solution in alcohol), ionone, isobutyl anthranilate, isobutyl butyrate, lemon essential oil, maltol, 4-methylacetophenone, methyl anthranilate, methyl benzoate, methyl cinnamate, methyl heptine carbonate, methyl naphthyl ketone, methyl salicylate, mint essential oil, neroli essential oil, nerolin, neryl isobutyrate, orris butter, phenethyl alcohol, rose, rum ether, undecalactone, vanillin and solvent.”


FDA-APPROVED STRAWBERRY FLAVORING!YUCK!!!


ARTIFICIAL FLAVORS, PRESERVATIVES & DYES, OH MY!


ARTIFICIAL FLAVORS, PRESERVATIVES & DYES, OH MY!

• Artificial dyes and preservatives can be huge behavioral triggers• Harmful behavior effects in kids in general, not just kids with ADHD• 2011 FDA review of studies:

• “Exposure to food and food components, including artificial food colors and preservatives, may be associated with adverse behaviors, not necessarily related to hyperactivity, in certain susceptible children with ADHD and other problem behaviors, and possibly in susceptible children from the general population.”

• 1 in 3 kids with ADHD may respond to a diet that eliminates artificial food dyes!!!

• EU requires warning label on foods with artificial food dyes that they:• “may have an adverse effect on activity and attention in children.”


PHENOL/SALICYLATE/FOOD ADDITIVE SENSITIVITY

• Phenols – natural chemicals made up of a benzene ring with one or more hydroxyl (OH) groups attached to it

• Almost ALL foods have phenols to some degree• Salicylates – phenol + carbohydrate group (COOH)

• Very similar to manmade acetylsalicylic acid – Aspirin • Often concurrent to sensitivity to artificial additives• Elimination of phenols, salicylates and food additives/colorings found to be

beneficial for kids with autism, ADHD, and behavioral problems• The Feingold Diet (https://feingold.org/)


https://feingold.org/

PHENOL/SALICYLATE SENSITIVITY• Common symptoms (similar to Histamine symptoms)

• Dark circles under eyes• Red face/ears after eating• Focus/attention problems• Hyperactivity • Headaches• Irritability/aggression• Trouble falling and staying asleep• Inappropriate laughter• Hives• Daytime and nocturnal enuresis• Tics• Sensitivity to NSAIDs

• Diagnosis: Elimination of moderate-high phenol/salicylate containing foods• Treatment: Avoidance of high-phenol/salicylate foods, heal the gut@2019 Elisa Song, MD - Healthy Kids Happy Kids

FOODS HIGH IN PHENOLS/SALICYLATES

@2019 Elisa Song, MD - Healthy Kids Happy Kids Think COLORFUL…

FOODS HIGH IN PHENOLS/SALICYLATES

• Fruits: Raisins, prunes, apricots, avocado, blackberries, blueberries, cherries, cranberries, grapes, pineapples, plums, oranges, tangerines, strawberries and guava.

• Vegetables: Broccoli, cucumbers, okra, chicory, endive, radish, zucchini, watercress, alfalfa sprouts, eggplant, squash, sweet potato, spinach, artichokes and broad beans.

• Spices: Curry, aniseed, cayenne, dill, ginger, allspice, cinnamon, clove, mustard, cumin, oregano, pimiento, tarragon, turmeric, paprika, thyme and rosemary.

• Other sources: Tea, rum, wine, cordials, vinegar, gravies, mints, almonds, water chestnuts, honey, licorice, jam, chewing gum, pickles, olives and olive oil, food colorings, aloe vera, savory-flavored chips and crackers and fruit flavorings.A great resource: http://salicylatesensitivity.com/about/food-guide/


http://salicylatesensitivity.com/about/food-guide/

THE CELL DANGER RESPONSE –TYING IT ALL TOGETHER

Elisa Song, MD - BioCeuticals Seminar 2019

THE HEALING CYCLE & THE CELL DANGER RESPONSE

• Described by Dr. Robert Naviaux at UC San Diego• The 4 discrete stages of the HEALING CYCLE

• The Health Cycle with wakeful activity, restorative sleep, seasonally-appropriate diet from local ecosystems

• 3 stages of the Cell Danger Response initiated by a cellular injury• CDR is an ADAPTIVE primitive protective response to chemical, physical,

microbial, or psychological threats• When cells go through the CDR and HEAL

• MITOCELLULAR HORMESIS cellular memory of how to deal with physiological and psychological threat the next time…

• Cellular resilience they learn how to do it better the next time



Fig. 1. A metabolic model of the health and healing cycles. Health is a dynamic process that requires regular cycling of wakeful activity and restorative sleep. The healing or damage cycle is activated when the cellular stress exceeds the capacity of restorative sleep to repair damage and restore normal cell-cell communication. CDR1 is devoted to damage control, innate immunity, inflammation, and clean up. CDR2 supports cell proliferation for biomass replacement, and blastemaformation in tissues with augmented regeneration capacity. CDR3 begins when cell proliferation and migrationhave stopped, and recently mitotic cells can begin to differentiate and take on organ-specific functions.Abbreviations: eATP; extracellular ATP; CP1–3: checkpoints 1–3; DAMPs: damage-associated molecular patterns; DARMs: damage-associated reactive metabolites.

https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/cell-stress

https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/innate-immunity

https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/biomass

https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/blastema

https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/cell-migration

THE CELL DANGER RESPONSE –PHASE 1

• Goal: Activate innate immunity, detect and remove threats, control and contain damage, repair the cell

• Cells become autonomous, to contain the threat and repair the cell while protecting the host

• Exposure to a threat triggers mitochondria to release ATP from the cell• Extra-cellular ATP binds to purinergic receptors on cell plasma

membranes• INITIATES THE CELL DANGER RESPONSE



• Purinergic receptors• Implicated in learning and memory, locomotor and feeding behavior

and sleep• Found on almost every cell in our body – including MAST CELLS

• ATP causes mast cells to degranulate• Mast cells release histamine and ATP

• Histamine vasodilates to recruit 02 and immune cells to site of inflammation

• ATP triggers further mast cell degranulation

Mitochondrial dysfunction & mast cell activationElisa Song, MD - BioCeuticals Seminar 2019


• Goal: Stem cell recruitment to replace cells lost during CDR1, “wall off” any damaged areas or persistent infections with scar tissue not completely cleared by CDR1

• The “clean-up” phase



• Functional medicine approaches to support normalization of these persistent cascades are important in this stage:

1. MAKE SURE THE THREAT IS ELIMINATED2. Mitochondrial dysfunction – coQ10, carnitine, ribose, antioxidants3. Mast cell activation/histamine intolerance – luteolin, quercetin,

DAO, cromolyn sodium, ketotifen4. Methylation dysfunction – MTHF, mB12, SAM5. Sulfur metabolism dysregulation – glutathione6. Vitamin D inactivation – Vitamin D3 7. Vitamin B6 reduction – P-5-P8. Gut dysbiosis, leaky gut & gluten sensitivity – 5R program, gluten

elimination



• GOAL: Cellular differentiation of new cells regenerated in CDR2, restore cell-cell communication, metabolic memory, adaptive immunity, detoxification

• Cells that were autonomous in CDR1 and CDR2 must now re-establish communication with the brain via the VAGUS NERVE

• Purinergic signaling and decrease in extracellular ATP is the major signal to cells that they are ready to reenter the HEALTH CYCLE

• Movement of CDR3 Health Cycle often results in IMPROVED baseline physiologic performance than before the injury/stress

• Mitocellular hormesis and metabolic memory more RESILIENT cells

Stress can be ADAPTIVE if cells are able to complete the HEALING CYCLEElisa Song, MD - BioCeuticals Seminar 2019

PERSISTENT CELL DANGER RESPONSE

• Abnormal persistence of CDR, even once the threat has been neutralized underlies many pediatric and adult chronic conditions

• Cells are unable to complete the Healing Cycle & reenter the Health Cycle• Autism, ADHD, PANS/PANDAS, asthma, atopy, autoimmune disease (lupus, MS,

rheumatoid arthritis, Alzheimer and Parkinson disease, bipolar, schizophrenia, PTSD, traumatic brain injury

Persistent maladaptive metabolic changes

Persistent MITOCHONDRIAL DYSFUNCTION and MAST CELL ACTIVATION

CHRONIC DISEASEElisa Song, MD - BioCeuticals Seminar 2019

WHEN THE CELL DANGER RESPONSE GETS STUCK

• Treatment may require anti-purinergic drugs or supplements• i.e. Suramin (100-year old antipurinergic drug for African Sleeping

Sickness)• Dr. Naviaux trial of 10 boys with ASD – single IV infusion of suramin

20mg/kg vs. saline significant improvements in language, social interaction, and decreased restricted or repetitive behaviors

• Suramin NOT available for clinical use…


ENERGY(ENERGY REGULATION, MITOCHONDRIAL FUNCTION)


THE MIGHTY MITOCHONDRIA• “Powerhouses” of our cells

• ATP produced by:• Kreb’s (citric acid) cycle in the

mito matrix)• Electron transport chain on the

inner membrane coQ10 – is cofactor

• Mitochondrial disorder vs. Mitochondrial dysfunction

• Inherited vs. acquired through toxic insult

• Clinical symptoms appear AFTER a cellular stressor – physiologic or psychologic

• Mitochondrial DNA is inherited from our MOTHERS (usually…)• Contain their own circular mtDNA @2019 Elisa Song, MD - Healthy Kids Happy Kids

@2019 Elisa Song, MD - Healthy Kids Happy Kids https://www.researchgate.net/publication/233737352_Cellular_and_molecular_mechanisms_of_mitochondrial_functionwww.gdx.net

https://www.researchgate.net/publication/233737352_Cellular_and_molecular_mechanisms_of_mitochondrial_function

http://www.gdx.net/

MITOCHONDRIAL DYSFUNCTION –HISTORY

• Baby• Poor suck and swallow at breast

or bottle• Poor head control (head lag

should resolve by 4 months)• Feeling that baby is “slipping

through the hands” when held under the arms

• “Rag-doll” posture when held under belly

@2019 Elisa Song, MD - Healthy Kids Happy Kids Photo credit: Casemed.case.edu

MITOCHONDRIAL DYSFUNCTION –HISTORY

• Sitting in “W” position• Rounded back when sitting• Weak pencil grasp• Low core strength (difficulty pumping

swing, sitting up from lying supine)• Persistent drooling• Clumsiness• Weakness• Low energy• Easy fatigue/Poor endurance

physically and mentally

• Muscle aches• Constipation• Speech/articulation issues• Hyperlaxity of the joints• Multiple regressions after illness or

medications/biologics


LAB EVIDENCE OF MITOCHONDRIAL DYSFUNCTION

• Elevated AST, ALT• Elevated creatine kinase (CK) • Elevated lactate (performed STAT)• Elevated pyruvate (performed STAT)• Elevated fasting ammonia (performed STAT)• Decreased free and total carnitine• Abnormal acylcarnitine profile• Decreased or suboptimal coenzyme Q10• Fasting plasma amino acids: high alanine or Alanine:Lysine > 3• Abnormal urine organic acid mitochondrial markers


MITOTOXIC INSULTS -MEDICATIONS

• Nitrous oxide• Valproate (Depakote)• Fluoxetine (Prozac)• Risperidone (Risperdal)• Alprazolam (Xanax)• Diazepam (Valium)• Acetaminophen (Tylenol)• Naproxen (Aleve)• Tetracycline/minocycline• Metformin • MSG

• Statins• Rifampin• Vaccines? (Hannah Poling case)


MITOTOXIC INSULTS

• Infections• EBV, HSV, Influenza A virus,

CMV, Hep B, Lyme and coinfections, HIV, etc.

• Heavy metals• Mercury, lead, arsenic,

aluminum, cadmium• Pesticides (Glyphosate)• Hypoxia• Poor nutrition• Propionic acid from clostridia

• Psychological trauma• Sleep deprivation• Alcohol/cigarette smoke• Dehydration


MITOCHONDRIAL SUPPORTS• Reduce mitochondrial stressors

• Excessive exercise• Fasting and dehydration• Extreme temperatures• Altitude• Heavy metals, vaccines, certain medications, and

other mito-toxins• Supplement with cofactors of Mitochondrial respiratory

chain complex• Coq10 as ubiquinol (up to 30 mg/kg/day)• L-carnitine (up to 100 mg/kg/day)• D-Ribose • B-vitamins• Phospholipids (PS, PC)

• “Strength” training exercise to build more mitochondria• Antioxidants to counter increased oxidative stress

• Eat a rainbow• Vitamin A, Vitamin C, vitamin E, glutathione, ALA

• Sleep!!! @2019 Elisa Song, MD - Healthy Kids Happy Kids

DEFENSE & REPAIR(IMMUNE, INFLAMMATION, INFECTION)


HISTAMINE – WHY IS IT SUCH A BIG DEAL?


Because histamine receptors are found on every single cell in our body…

HISTAMINE/MAST CELL ACTIVATION –DOES EVERYONE HAVE IT?

• Clues for histamine/mast cell concerns:• Dermatographism• Anxiety• Kids do worse on fermented foods• Facial flushing• Heat intolerance• Tachycardia • Eczema, hives, asthma, allergies other signs of histamine overload• Reflux, nausea, vomiting, diarrhea• Abdominal pain• Headaches, dizziness• Fatigue, sleep disturbance• Changing reactivity to foods• Sensitivity to NSAIDs


HISTAMINE/MAST CELL ACTIVATION –LAB WORKUP

• Suggestive lab findings• Total IgE• Eosinophil count• Plasma histamine• Serum tryptase

• >20 ng/ml for MCAD• OR 20% above basal serum tryptase + 2ng/ml

• Eosinophil cationic protein• Stool eosinophil protein X


HISTAMINE/MAST CELL ACTIVATION –TREATMENT

• Reduce high histamine foods and histamine-releasing foods• SUGAR• Artificial flavors, colors, preservatives• Chocolate, wine, strawberries, avocados, bananas, dairy, eggs, oranges,

peaches, pineapples, raspberries, spinach, and tomatoes.• ?Fermented foods• Dr. Janice Jonega: Histamine and Tyramine Restricted Diet

• https://www.jillcarnahan.com/downloads/HistamineRestrictedDiet.pdf

• Increase foods high in quercetin• Raw onion, apples (skin), red grapes, kale, spinach, capers, watercress, cherries,

green tea, bee pollen, chili peppers• Stabilize blood sugar/insulin response


https://www.jillcarnahan.com/downloads/HistamineRestrictedDiet.pdf

HISTAMINE/MAST CELL ACTIVATION –TREATMENT

• DAO and/or cromolyn sodium before meals• Luteolin, PEA, quercetin, ketotifen• Chinese skullcap (Scutellaria baicalensis or Baikal skullcap)• Vitamin C• Zinc • Low-dose naltrexone• CBD oil• H1-histamine blocker

• Cetirizine not anticholinergic like loratadine and diphenhydramine• Anticholinergic medications linked to increased dementia risk

• H2-histamine blocker• Address resulting gut dysbiosis


COMMUNICATION(ENDOCRINE, NEUROTRANSMITTERS, IMMUNE MESSENGERS)


THE VAGUS NERVE…

• Activate the vagus nerve• Get out of Fight-Flight-Freeze (Sympathetic)• Get into Rest-Digest-Heal (Parasympathetic)

• READ:• The Polyvagal Theory by Stephen W. Porges• Accessing the Healing Power of the Vagus Nerve by Stanley Rosenberg


HOW TO ACTIVATE THE VAGUS NERVE

• Meditation/Mindfulness• Belly breathing (Diaphragmatic breathing)• Heartmath - HRV• Auricular acupuncture

• Electrostimulation• Ear seeds

• Gargling


OMMM… PRACTICE MINDFULNESS

Mindfulness can be practiced anywhere…STOP, LOOK, & LISTEN…

Elisa H. Song, MD - Healthy Kids Happy Kids

STOP, LOOK & LISTEN

• Stop what you’re doing, even for just 1 minute• Look and really notice what’s happening around you with all of your 5 senses

– What do you see? What do you hear? What do you feel on your skin? What do you smell? What do you taste?

• Listen to your body & mind and notice everything you’re experiencing and feeling in that moment.


MINDFULNESS/STRESS REDUCTION RESOURCES

BOOKS:• What To Do When You Worry too Much by Dr. Dawn Huebner • The Goodnight Caterpillar: A children’s relaxation story by Lori Lite

Apps/Online programs:• Stop, Breathe & Think Kids• GoZen (www.gozen.com) • Calm (kids’ section)

CDs:• Still Quiet Place: Mindfulness for young children and Still Quiet Place:

Mindfulness for teens by Dr. Amy Saltzman


http://www.gozen.com/

BREATHE…• Diaphragmatic “belly breathing” to activate of the vagus nerve

• Get out of fight-flight-freeze• Get into rest-digest-heal…


• Diaphragmatic breathing benefits:• Lower cortisol • Increased HRV• Increased energy, alertness,

relaxation, mood• Decreased anxiety, depression,

anger, confusion

Zaccar A et al. How Breath-Control Can Change Your Life: A Systematic Review on Psycho-Physiological Correlates of Slow Breathing. Front Hum Neurosci. 2018 Sep 7;12:353. doi: 10.3389/fnhum.2018.00353

https://www.ncbi.nlm.nih.gov/pubmed/30245619

BELLY BREATHING• Sit or lie comfortably• Place one hand on chest• Place the other hand on belly• Pretend there’s a balloon in their belly that they need to inflate every time

you take a deep inhale, and deflate fully with every exhale• Breathe in through their nose and fill that balloon, noticing the hand on their

belly rise, and the hand on their chest staying still• Breathe out through their mouth, feeling the hand on their belly sink all the

way down, while the hand on their chest remains still

Sesame Street: Common and Colbie Caillat – “Belly Breathe” with Elmohttps://www.youtube.com/watch?v=_mZbzDOpylA


https://www.youtube.com/watch?v=_mZbzDOpylA

JUST BREATHE…


The ONE thing your kids need to know to THRIVE…

http://bit.ly/BreatheKids

http://bit.ly/BreatheKids

THANKS FOR JOINING ME TODAY!Questions?

ZINC REFERENCES• https://www.uptodate.com/contents/zinc-deficiency-and-supplementation-

in-children-and-adolescents• https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/• Yagi T et al. The role of zinc in the treatment of taste disorders. Recent Pat

Food Nutr Agric. 2013 Apr;5(1):44-51.• Ohinata K et al. Orally administered zinc increases food intake via vagal

stimulation in rats. J Nutr. 2009 Mar;139(3):611-6. doi: 10.3945/jn.108.096370.• Henkin RI. Zinc in taste function: a critical review. Biol Trace Elem Res. 1984

Jun;6(3):263-80. doi: 10.1007/BF02917511.• Suzuki H et al. Zinc as an appetite stimulator – the possible role of zinc in the

progression of diseases such as cachexia and sarcopenia. Recent Pat Food Nutr Agric. 2011 Sep;3(3):226-31.

• Yanagisawa H et al. Validity of the copper/zinc ratio as a diagnostic marker for taste disorders associated with zinc deficiency. J Trace Elem Med Biol. 2016 Jul;36:80-3. doi: 10.1016/j.jtemb.2016.04.012.


https://www.uptodate.com/contents/zinc-deficiency-and-supplementation-in-children-and-adolescents







ZINC REFERENCES• Guillermo V et al. Zinc in Gut-Brain Interaction in Autism and Neurological

Disorders. Neural Plast. 2015; 2015: 972791. doi: 10.1155/2015/972791• Yasuda H, et al. Infantile zinc deficiency: association with autism spectrum

disorders. Sci Rep. 2011;1:129. doi: 10.1038/srep00129• McAllister BB and RH Dyck. A new role for zinc in the brain. eLife. 2017; 6:

e31816. doi: 10.7554/eLife.31816• Bloch MH and J Mulqueen. Nutritional Supplements for the treatment of

Attention-Deficit Hyperactivity Disorder. Child Adolesc Psychiatr Clin N Am. 2014 October ; 23(4): 883–897. doi:10.1016/j.chc.2014.05.002.

• Pfeiffer CC Braverman ER. Zinc, the brain and behaviour. Biol Psychiatry 1982;17(4):513-532.

• Kumar M et al. Fine control of sound frequency tuning and frequency discrimination acuity by synaptic zinc signaling in mouse auditory cortex. J Neurosci. 2019: 39 (5) 854-865; DOI: https://doi.org/10.



https://dx.doi.org/10.1155%2F2015%2F972791

https://www.ncbi.nlm.nih.gov/pubmed/22355646/


https://dx.doi.org/10.7554%2FeLife.31816

ZINC REFERENCES

• Barrie SA et al. Comparative absorption of zinc picolinate, zinc citrate and zinc gluconate in humans. Agents Actions. 1987 Jun;21(1-2):223-8.

• Marone G et al. Physiological concentrations of zinc inhibit the release of histamine from human basophils and lung mast cells. Agents Actions. 1986 Apr;18(1-2):103-6.

• Sturnio GC et al. Zinc supplementation tightens “leaky gut” in Crohn’s disease. Inflamm Bowel Dis. 2001 May;7(2):94-8.

• Miyoshi Y et al. Cellular zinc is required for intestinal epithelial barrier maintenance via the regulation of claudin-3 and occludin expression. Am J Physiol Gastrointest Liver Physiol. 2016 Jul 1;311(1):G105-16. doi: 10.1152/ajpgi.00405.2015.

• Tran CD et al. Zinc-fortified oral rehydration solution improved intestinalpermeability and small intestinal mucosal recovery. Clin Pediatr (Phila). 2015 Jun;54(7):676-82. doi: 10.1177/0009922814562665.







MAGNESIUM REFERENCES• https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/#h5• Sun-Edelstein C, Mauskop A. Role of magnesium in the pathogenesis and

treatment of migraine. Expert Rev Neurother 2009;9:369–79.• Yablon LA and A Mauskop. Magnesium in headache. In Vink R, Nechifor M,

editors. Magnesium in the Central Nervous System [Internet]. Adelaide (AU): University of Adelaide Press; 2011.

• Abbasi B et al. The effect of magnesium supplementation on primary insomnia in elderly: a placebo-controlled clinical trial. J Res Med Sci. 2012 Dec;17(12):1161-9.

• Sartori SS et al. Magnesium deficiency induces anxiety and HPA axis dysregulation: Modulation by therapeutic drug treatment. Neuropharmacology. 2012 Jan; 62(1): 304–312. doi: 10.1016/j.neuropharm.2011.07.027


https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/#h5

https://www.ncbi.nlm.nih.gov/pubmed?term=Vink%20R%5BEditor%5D

https://www.ncbi.nlm.nih.gov/pubmed?term=Nechifor%20M%5BEditor%5D



https://dx.doi.org/10.1016%2Fj.neuropharm.2011.07.027

MAGNESIUM REFERENCES

• Mlyniec K et al. Essential elements in depression and anxiety. Part I. Pharmacol Rep. 2014 Aug;66(4):534-44.

• Egy GA and KL Eby. Rapid recovery from major depression using magnesium treatment. Med Hypotheses. 2006;67(2):362-70.

• Black LJ, Allen KL, Jacoby P, et al. Low dietary intake of magnesium is associated with increased externalising behaviours in adolescents. Public Health Nutr 2015;18(10):1824-1830.


IRON REFERENCES• https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/• https://www.uptodate.com/contents/iron-deficiency-in-infants-and-children-

less-than12-years-screening-prevention-clinical-manifestations-and-diagnosis• Sheriff A et al. Should infants be screened for anaemia? A prospective study

investigating the relation between haemoglobin at 8, 12, and 18 months and development at 18 months. Arch Dis Child. 2001;84(6):480.

• Alterman JS et al. Iron deficiency and cognitive achievement among school-aged children and adolescents in the United States. Pediatrics. 2001;107(6):1381.

• Carter RC et al. Iron deficiency anemia and cognitive function in infancy. Pediatrics. 2010;126(2):e427.

• Algarin C et al. Iron-deficiency anemia in infancy and poorer cognitive inhibitory control at age 10 years. Dev Med Child Neurol. 2013 May;55(5):453-8.


https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/

https://www.uptodate.com/contents/iron-deficiency-in-infants-and-children-less-than12-years-screening-prevention-clinical-manifestations-and-diagnosis

IRON REFERENCES• Lozoff B et al. Dose-response relationships between iron deficiency with or without

anemia and infant social-emotional behavior. J Pediatr. 2008;152(5):696• Choudhury V et al. Latent iron deficiency at birth influences auditory neural

maturation in late preterm and term infants. Am J Clin Nutr. 2015 Nov;102(5):1030-4.• Algarin C et al. Iron deficiency anemia in infancy: long-lasting effects on auditory

and visual system functioning. Pediatr Res. 2003;53(2):217.• Amin SB et al. Latent iron deficiency in utero is associated with abnormal auditory

neural myelination in≥35 weeks gestational age infants. J Pediatr. 2013;163(5):1267.• Lozoff B et al. Double burden of iron deficiency in infancy and low socioeconomic

status: a longitudinal analysis of cognitive test scores to age 19 years. Arch Pediatr Adolesc Med. 2006;160(11):1108.

• Lukowski AG et al. Iron deficiency in infancy and neurocognitive functioning at 19 years: evidence of long-term deficits in executive function and recognition memory. Nutr Neurosci. 2010;13(2):54.


IRON REFERENCES

• Congdon EL et al. Iron deficiency in infancy is associated with altered neural correlates of recognition memory at 10 years. J Pediatr. 2012;160(6):1027.

• Lozoff B et al. Functional significance of early-life iron deficiency: outcomes at 25 years. J Pediatr. 2013 Nov;163(5):1260-6.

• Bruner AB et al. Randomised study of cognitive effects of iron supplementation in non-anaemic iron-deficient adolescent girls. Lancet. 1996;348(9033):992.

• Ballin A et al. Iron state in female adolescents. Am J Dis Child. 1992;146(7):803.• Rowland TW et al. The effect of iron therapy on the exercise capacity of nonanemic

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