NUTRITION, THE GUT AND MENTAL HEALTH SCOTT SHANNON, MD FAACAP MARY - - PowerPoint PPT Presentation

NUTRITION, THE GUT AND MENTAL HEALTH

SCOTT SHANNON, MD FAACAP MARY RONDEAU, ND, RH(AHG)

DISCLOSURES

• Dr Shannon has published two textbooks on integrative mental

health and two on parenting.

• Dr. Shannon is a PI/researcher on The Phase III MDMA assisted

psychotherapy in PTSD study and receives support for clinical work from Multidisciplinary Association for Psychedelic Studies (MAPS), a 501c3 non profit through MAPS Public Benefit Corp

• Dr. Rondeau has no conflicts

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OVERVIEW

• Diet
• Population studies
• Gluten
• Microbiome: communication and health
• Dysbiosis and disease
• Physical and Mood Symptoms
• Laboratory considerations
• Treatment considerations

JAMA Psychiatry. 2018;75(9):918-928.

BUILD A BRAIN

• Grain fortification with folic acid took effect 1/98
• Rapidly doubled folic acids levels in pregnant women
• Compared MRI scans of 1,370 youths (pre/post/during)
• Exposure related cortical thickness changes found
• Also correlated with reductions in psychosis risk

Eryilmaz H et al JAMA Psychiatry. 2018 Sep 1;75(9):918-928.

Date of download: 1/7/2019

From: Association of Prenatal Exposure to Population-Wide Folic Acid Fortification With Altered Cerebral Cortex Maturation in Youths

JAMA Psychiatry. 2018;75(9):918-928. doi:10.1001/jamapsychiatry.2018.1381

NUTRITIONAL PSYCHIATRY

• Consistent studies: diet quality related to risk of depression and
• ther MH issues
• Concurrently, data point to the utility of selected nutraceuticals as

adjunctive treatments

• New studies… are pointing to the immune system, oxidative biology,

brain plasticity and the microbiome-gut-brain axis as key targets

• Increased Western diet and decreased traditional diet are inversely

and separately linked to MH

Jacka, F EBio Medicine 2017, Mar; 17: 24–29.

POPULATION STUDIES

DIET AND PEDS MH

• Systemic Review: 12 relevant studies
• We found evidence of a significant, cross-sectional

relationship between unhealthy dietary patterns and poorer mental health in children and adolescents.

• We observed a consistent trend for the relationship

between good-quality diet and better mental health and some evidence for the reverse.

O’Neil, A AJ Public Health 2014 October; 104(10): e31–e42.

WE NEVER KNOW FOR SURE

DIET QUALITY & MOOD

• Traditional diet reduces:
• Depression
• Bipolar disease
• Anxiety
• Traditional diet includes:
• High in veggies
• Fruits
• Whole grains
• Fish
• Meat

Jacka, FN Psychosomatic Medicine 2011; 73 (6): 483-90 Jacka, FN J Affective Disorder 2011; 129 (1): 332-7

ADOLESCENTS AND MENTAL HEALTH

• Prospective study of 3,040 Australian youth aged 11 to 18
• ver 3 years
• Diet quality associated with better mental health
• Improving diet: improved mental health
• Deteriorating diet: worse mental health
• Patterns do not support reverse causality

Jacka, FN PLoS 2011 ; 6 (9): e 24805.

DIET QUALITY AND PEDIATRIC MH

• Prospective multi-national study of 7,675 children ages 2-9

Followed 2 years Fruit and veg intake: improved well-being Fish intake: imp self-esteem and fewer peer problems “Children’s physical and mental development is dependent on nutritional quality”

Arvidsson, L BMC Public Health 2017 Dec 17(1):926

CHANGING FATTY ACID RATIO: OMEGA 6 TO OMEGA 3

• Prehistoric

~ 1900 ~ 2000

• 1:1

4:1 25:1

n-6 fats n-3 fats

FATTY ACIDS AND MOOD

Pilot study: 38 children (11-17 yrs old) treated with emulsified

• mega-3.
• Significant reductions in Children’s depressive

inventory after 12 weeks. Trebaticka, JChild Adolesc Psychiatry Ment Health. 2017; 11: 30 Randomized, double-masked, crossover trial: 38 children.

• High palmitic acid (SAD diet) vs high oleic acid diet (Med diet).
• HOA group- more physically active and less angry
• High fat diet (palmitate) more mood disorders and correlates

positively with high serum palmitate

Kien, C American J Clin Nutrition 2013 97 (4): 689

16

CRUCIAL FOR MEMBRANE FLUIDITY

PRACTICAL: AVOID OMEGA 6 INTAKE

• However, the higher consumption of Linoleic acid, as

now seen in the Western diet, shows an increase in the preference of these enzymes to metabolize n-6 PUFA, leading to AA synthesis, despite the fact that these enzymes show higher affinity for n-3 PUFA.

Patterson E et al. J Nutr Metab. 2012: 539426

25 50 75 100

Ca Mg Fe Cu Na K P

81 65 78 19 57 86 94 Percent of 1947 Level 1947 1997

Mayer, A B. Historical Changes in the Mineral Content of Fruit and Vegetables. British Food Journal 99(6). 1997. 207- 211.

Decrease in Mineral Content In Vegetables Over 50 Years

BLOOD SUGAR

• Up and down rollercoaster
• High intake refined carbohydrates -->blood

sugar increases--> quickly metabolized--> sharp decline in available glucose for brain = symptoms

Wenzel K-G: Orthomolecular Treatment for Mental Health: The Roles of Hypoglycemia, Pyrroluria and Histamine Disturbances. 2000

• Apr. Nutritional Medicine Today 29th Annual Conference. Vancouver, BC.

Rao J, Oz G, Seaquist ER: Regulation of cerebral glucose metabolism. Minerva Endocrinol, 2006 Jun; 31(2): 149-158. Hoffer A: Orthomolecular Medicine for Physicians. New Canaan, CT. Keats Publishing. 1989.

FOOD SENSITIVITY SYMPTOMS

• Allergic shiners
• Hx of colic
• Hx of eczema
• Hx of reflux
• Bad breath
• Foot odor
• Hx of otitis
• Acne
• Family hx atopy
• Runny nose
• Insomnia
• Abdominal pain, IBS
• Joint pain
• Migraine/ headache
• Congestion
• Flushed cheeks/ears

ELIMINATION DIET AND ADHD

• Open label phase followed by RCT crossover

challenge phase

• 100 children, 4-8 yrs with ADHD
• Elimination diet (based on IgG) vs healthy diet
• Responders challenged with high IgG foods. 63%

relapsed

• Conclusion: strictly supervised restricted elimination

diet is a valuable instrument to assess whether ADHD is induced by food

Pelsser LM et al Lancet, 2011; 5:377(9764): 494-503.

DIET AND ADHD

Meta analyses: ADHD and diet

• Artificial food coloring = More studies needed
• Food elimination = The effect size is

substantial, offering treatment opportunities in subgroups of children with ADHD

PLoS One. 2017 Jan 25;12(1)p-;

Diet and ADHD, Reviewing the Evidence: A Systematic Review of Meta-Analyses of Double-Blind Placebo- Controlled Trials Evaluating the Efficacy of Diet Interventions on the Behavior of Children with ADHD.

GLUTEN: FRIEND OR FOE?

GLUTEN

• Celiac Disease linked to increased rates of:
• CNS Disease-ataxia, dementia, vasculitis, encephalitis, epilepsy,

migraine

• Psych Disease-ADHD, depression, anxiety, suicide,

eating d/o, schizophrenia and autism

• Linked to increased risk for infertility, osteoporosis, Lupus,

RLS, anemia

• 30% of population genetically vulnerable: HLA DQ2 and DQ8

Cascella NG Schizophr Bull 2011 37 (1): 94-100

GLUTEN SENSITIVITY

• Milder variation of CD
• CD represents tip of the iceberg
• Most CD is undiagnosed
• As we age more convert to sensitivity or CD
• Rates of CD rising rapidly? Now close to 1%
• Rates of GS? 10% of population or more???
• Tests not very good for GS: Elimination diet!

Ann Nutr Metab. 2015;67 Suppl 2:16-26. doi: 10.1159/000440990. Epub 2015 Nov 26. Gluten Sensitivity.

FIVE FOLD RISE IN CD

• Followed 3,511 patients from 1974 to

1989

• During this 15 year period the rate of

CD rose 5 fold in the followed patients

• Significant percentage of adults lost

gluten tolerance over 15 year period

• Gluten sensitivity may be acquired and

not just inherited/congenital

Catassi C, Ann Medicine 2010 42 (7): 530-8.

CNS MECHANISM FOR GLUTEN?

• Cerebral perfusion studied in 3 groups:

CD on no diet, CD on gluten free diet and controls

• CD on no diet: 73% had one or more

brain regions with marked hypoperfusion

• No differences between other two

groups

Addolorato G, Am J Medicine 2004 116 (5): 312-7.

ANTI-GLIADIN AND AUTISM

• 57 children dx with Autism
• Significantly higher IgG anti-gliadin than controls
• No difference in celiac markers
• More pronounced IgG anti-gliadin in children with GI

symptoms

Lau, NM PLoS One 2013. 8(6): e66155

GLIADIN ANTIBODIES AND PSYCHOSIS

• Analyzed archival blood samples from

newborns born 1975 to 1985.

• Registry of patients with non-affective

psychosis and matched controls.

• Assessed for IgG antibodies to gliadin

and casein.

• Significance for gliadin but not for

casein.

Karlsson H, Am J Psychiatry 2012 169 (6): 625-32.

POSSIBLE MECHANISMS

• Gut dysfunction: inflammation/malabsorption-gliadin triggers

the release of zonulin (breaks down intestinal tight junctions)

• CNS perfusion
• Immunological shift: TH1/TH2 balance
• Immunological sensitization: gliadin and autoimmunity-cross

reactivity

• Gliadin exorphins: partial breakdown products with CNS
• piate activity
• Wheat, dairy and soy contain high levels of excitotoxins:

glutamic acid and aspartic acid trigger NMDA and other receptors

THE MICROBIOME

MICROBIOME

• The body has approximately
• 10 trillion human cells
• 100 trillion bacteria
• 1,000 trillion virus
• Outnumber human cells 10:1 and genes 100:1

J Transl Med. 2017; 15: 73.

DEFINITION

• Gut-Brain Axis
• “an interaction that consists of bidirectional

communication between the central and enteric nervous system, linking emotional and cognitive centers of the brain with peripheral intestinal

• function. This interaction occurs through

signaling to and from gut-microbiota and brain, by means of neural, endocrine, immune and humoral connections.

• Ann. Gastroenterol. 2016; 29(2):240

THE GUT AND BRAIN INFLUENCES ONE ANOTHER

• Intestinal bacteria

change thoughts and mood AND...

• Thoughts and mood

change the composition of the gut microbiota

COMMUNICATION

Flux MC, Lowry CA, 2019, Finding intestinal fortitude: Neurobiology of Disease, 2020 Feb;135:104578.

GUT PHENOTYPES

Valles-Colomer et al. Nature Microbiology, 2019, 4: 623-632.

GUT AND PSYCH SYMPTOMS

• 111 adult inpatients admitted for psychiatric crisis assayed with 16S

rRNA gene sequencing and whole genome shotgun sequencing

• Depression and anxiety severity: negatively associated with bacterial

richness and alpha diversity.

• bacterial taxa associated with depression and anxiety severity.
• Gut microbiota richness and alpha diversity: significant predictor of

depression remission at discharge.

Madan, N et al J Affective DO 2020 Mar 1;264:98-106

GUT MICROBIOTA CHANGES BRAIN DEVELOPMENT

• 5 different brain regions, found 40 genes

that were affected by presence of gut bacteria.

• These affected nerve cells and influenced

genes to be turned off or turned on

• Germ free mice were hyperactive and

lower anxiety (disinhibited)

• Life long changes from early alteration

Diaz Heijtz R, PNAS, 2011 108 (7): 3047-52

IMPORTANCE OF GUT MICROBES

• ASD population higher levels of Clostridria histolyticum . ASD

children had 9 species of Clostridia not found in controls

• Altered gut microbes in chronic fatigue syndrome,

supplemented with 24 B units lactobacillus for 2 months = significant decrease in anxiety

• Bifidobacteria infantis could modulate tryptophan

metabolism and influence the pool for serotonin

• GI symptoms were strongly correlated with severity of

autism…lower levels of bifidobacter and higher levels of lactobacillius were found

J Med Microbiology 2005; Gut Pathog 2009 March; Br J Nutr 2011; J Psychiatr Res 43: 164-174; BMC Gastroenterol 2011; Clin Infect Dis. 2002

LIPOPOLYSACCHARIDE ENDOTOXIN (LPS)

• Structural portion of the external membrane of

gram-negative bacteria.

• LPS creates anxiety, cognitive deficits, depressive

symptoms at extremely low levels (0.4 ng/kg)

• Most people carry a gram or more of LPS in

intestinal lumen.

• LPS can create limbic system/amygdala excitotoxicity

Haba R et al Brain Behavior Research 2012 ; 228: 423-431

PSYCHOBIOTICS

• Live organism that offer benefit to psychiatric

illness.

• Depression associated with shift in range of
• rganisms
• Healthy aging relates to diversity of microbiota
• Mechanisms: anti-inflammatory, neurochemical,

calm HPA axis, dietary mediation

Dinan, T et al Biological Psychiatry 2013 74 (10): 720-726.

PSYCHOBIOTICS

• RCT of 132 pts. Significant improvements in mood

with Lactobacillus casei

• Placebo controlled trial of 39 pts with CFS. Significant

improvements in anxiety with Lactobacillus casei

• 44 pts with IBS noted significant improvements in

anxiety with Bifidobacteria

• 42 non-clinical adults given Lactobacillus helveticus and

Bifidobacterium longum in RCT noted reductions in anxiety and free cortisol.

Bested A et al Gut Pathology 2013 5(4): 1 -22

PHYSICAL SYMPTOMS OF GUT DYSBIOSIS

• Abdominal Pain
• Abnormal

stools

• Anorexia
• Belching
• Constipation
• Diarrhea
• Distention
• Dysphagia
• Flatulence
• Hemorrhoids
• Nausea
• Reflux
• Ulcers
• Vomiting

CANDIDA

• Randomized, placebo-controlled longitudinal pilot

study 56 pts w schizophrenia

• Probiotic treatment significantly reduced C.

albicans antibodies over 14 weeks in males. Trend

• f improving psychiatric sx in males
• Results: association of C. albicans seropositivity

with worse positive psychiatric symptoms (confirmed with larger cohort 384 males w schizophrenia)

Brain Behav Immun. 2017 May;62:41-45. doi: 10.1016/j.bbi.2016.11.019. Epub 2016 Nov 18.

Probiotic normalization of Candida albicans in schizophrenia: A randomized, placebo- controlled, longitudinal pilot study.

CANDIDA

• Case study: ADHD and Depression 3 year following
• Deterioration in psychiatric sx when infected with

Candida sx improvement with anti fungal tx (Olive leaf) and probiotics

• Micronutrient treatment might be severely

compromised by infections such as Candida and may highlight importance of gut health when treating psychiatric disorders with nutrients

Rucklidge, J Adv Mind Body Med. 2013, 27(3):14-8.

PROPOSED MECHANISMS GUT: BRAIN EFFECTS

• Reduction in lipid

peroxidates

• Direct microbial

neurochemical production

• Direct activation of neural

link: gut/brain-vagus nerve

• Limitation of cytokine

production

• Improvement of nutritional

absorption

• Modulation of neurotrophic

chemicals-BDNF, etc.

• Indirect influence on NT/

neuropeptide production

• Direct protection of

intestinal barrier

• Reduction of amine/

uremic burden

• Limitation of intestinal

pathogens

• Analgesic properties

Logan AC et al Medical Hypothesis 2005 64: 533-538.

LABORATORY

• Blood work: ferritin,

Vit D, homocysteine, CRP , GGT

• Organic Acid Test (OAT)
• Food Sensitivity/ Food Allergy-serum (IgG and IgE)
• Comprehensive Stool Analysis
• Celiac/gluten sensitivity
• Microbiome assays
• Genetic SNPs

TREATMENT: GI DYSBIOSIS

• Identify all factors in health imbalance
• Reactions: food, supplements, environment,

medicine, body care products etc

• Microbial imbalance
• Chemical burdens
• Genetic predispositions/ vulnerabilities
• Stress (physical, mental, emotional etc.)

TREATMENT: GI DYSBIOSIS

• Yeast vs Bacteria
• Antifungals Rx vs Antibiotics
• Herbals- olive leaf extract, caprylic acid, berberine plants, oil
• f oregano, garlic etc.
• Probiotics
• Gut healing nutrients
• Digestive support
• herbal or enzymes
• DIET!!!

CLINICAL ADVICE

• Avoid processed food
• Diet diversity is critical
• Think traditional patterns.
• Cook together and eat together
• Sugar craving/severe illness: Anti-fungals
• Supplementation: omegas and probiotics

CLINICAL ADVICE

• No soda; reduce chips and fries
• Add one fruit per day and one veggie per day
• Reduce sugar load
• High protein breakfast
• If allergic: consider elimination diet or gluten free,

dairy free trial

• Hypoglycemia: protein bars, nuts, etc…

SUMMARY

• Diet plays a role in mental health
• Diet should be incorporated into treatment plans
• Elimination diets can be useful for numerous

conditions

• The microbiome affects mental health
• Mental health status affects microbiome
• Assessment of gut health/microbiome can be a useful

adjunct treatment in mental health

CASE: PEDIATRIC BIPOLAR

• 5 yo Male, presents for “medications” to help with

behaviors at risk of being kicked out of kindergarten. Described as “completely out of control”, sensory concerns, poor sleep, encoporesis/constipation

• Past Medical: Numerous abx for chronic ear infections,

tonsils out at 3 yrs old, constipation, eczema

• PE:Dark circles, erythematous cheeks and ears, bloated

abdomen

CASE : PEDIATRIC BIPOLAR

• Labs: OAT:++yeast markers
• Tx: Fluconazole: x 10 days, digestive enzymes,

diet: GFCF, corn free and no sugar (yeast free diet)

CASE : PEDIATRIC BIPOLAR

• 1 month post treatment: Continues to do well in school. Sleep

11-12 hrs Encoporesis still issues- (However no pain with defecation), Erythematous cheeks and ears resolved

• 2 month post tx: Dietary changes continued. Continues to do
• well. Encoporesis resolved
• 3 months post tx: Diet associations with constipation,

behaviors, repeat yeast tx and reenforced diet.

MARY RONDEAU, ND
 SCOTT SHANNON, MD

• Wholeness Center
• 2620 E Prospect Rd. #190
• Fort Collins, Colorado 80525
• 970.221.1106
• scott@wholeness.com
• www.wholeness.com