10. Basic
Supplementation
Leaky Gut Syndrome
and functional
problems
Integrative nutritional
approach to digestive
tract disorders
More symtoms
•Children >6 years and
healthy adults
• Athlets
• Elderly
• Unbalanced diets
• Gut habits disorders
• Bloating
• Dysbiosis
• Chronic use of FANS
• Post-antibiotic therapy
• Post surgery
• Bariatric surgery
• Integrative nutritional
approach to digestive tract
disorders
Continuum from GI health to FGDs to IBD
Different approach for each condition
11. Sport → Gut microbiota
Gut microbiota -> Performance ?
20. Upper GI tract Lower GI tract
Delayed gastric empting (GE) Gut pain
GERD Bloating - gas
Burning Dhiarrea
Nausea - Vomit Blood in faecis
Eruttations Pain in the side abdomen
21. Is it possible to train the gut??
GI
Ecosystem
Digestion
Allergies and
intollerances
Inflammation
and oxidative
stress
GI
Apparatus
Strength
Resistence
Flexibility
Muscles
Joints and
bones
Stress
management
Focus
Motivation
Psyche
24. Pillars of funcional medicine and nutrition
GI Barrier
Microbiota
Mitochondria
Lipidomics Detox
Immunity
inflammation
Lipid Cho
Protein
Metabolism
Cuivre
VIT B12
Micronutrient
Deficiencies
Oxidative
stress
Neurotransmitters
Neuroprotection
25. Many micronutrients are commonly
used for GI support by amatorial and professional athletes..
- Probiotics
- Prebiotics
- Glutamine
- Vitamins
- Minerals
- Alfa lipoic acid
- EGCG
- Curcumin
- Digestive enzymes
- Herbal teas
- Ginger
- Water and salts
27. GI Barrier is a therapeutical target for
gastroenterologists and every health care pratictictioner
28. • Conditionally essential amino acid
• Necessary for the synthesis of DNA and RNA
• Necessary for cell division and renewal and for protein synthesis
• Necessary for the tissues that quickly renew themselves
• Necessary for the enterocytes and the intestinal barrier function
(tight junctions)
L-glutamine
• Wise et al. Glutamine: role in gut protection in critical illness. Curr Opin Clin Nutr Metab Care. 2006;9(5):607-12
• Fuentes et al. Metabolic role of glutamine and its importance in nutritional therapy. Nutr Hosp 199;11(4):215-25.
• dos Santos et al. Glutamine supplementation decreases intestinal permeability and preserves gut mucosa integrity
in an experimental mouse model. JPEN 2010;34(4):408-13
29.
30. Detoxication of xenobiotics
strengthening of the intestinal epithelium
impermeability
competitive barrier against
colonization/invasion
development, education and function of
the immune system
enhancement of the
digestive efficiency and
modulation of energy
homeostasis
vitamin synthesis
CNS modulation
Endocrine sistem modulation
programming of the circadian epigenetic and
transcriptional landscape
Probiotics
32. Per ogni obiettivo salutistico e terapeutico il ceppo
(o la miscela di ceppi) migliore è quella che fornisce
più evidenze cliniche di efficacia, visto che sicurezza e
capacità di colonizzare l’intestino sono un
prerequisito ▪ Intolleranza al lattosio
▪ Diversi tipi di diarree e gastroenteriti
- Diarrea infettiva (rotavirus, Clostridium difficile, proliferazione
batterica)
- Diarrea indotta da antibiotici
- Lesioni intestinali da chemioterapia
▪ Prevenzione delle allergie
▪ IBS e FGIDS
▪ Diarrea del viaggiatore
▪ Diminuzione delle allergie
▪ Malattie infiammatorie intestinali (Crohn, colite ulcerosa, pouchite)
▪ Prevenzione delle infezioni da Helicobacter pylori
▪ Prevenzione del cancro
▪ Infezioni virali
▪ Modulazione metabolica (met. Carboidrati, grassi)
+ + +
+ +
+
33. ° Associazione di ceppi di probiotici tra tra cui:
° Triplo cieco, randomizzato , controllato con placebo
° n = 503 : probiotici n = 336, placebo n = 167
° Adulti da 30 a 70 anni in trattamento con antibiotici
° Assunzione quotidiana dopo 7 ore dall’assunzione di antibiotico
“I probiotici diminuiscono I sintomi legati all’uso di antibiotici:
uno studio randomizzato dose-risposta”
Ouwehand AC, Donglian C, Weijian X, Stewart M, Ni J, Stewart T, Miller LE. Vaccine. pii:
S0264-410X(13)01587-9
L. Acidophilus NCFM®
B. Lactis Bi-07
Diarrea acuta
34.
35. Il nostro microbiota cambia secondo la nostra età
Conseguenze:
- Diminuzione funzionalità del sistema immunitario
Immunità ↓
aumenta il rischio di infezioni (es. respiratorie)
e si riduce l’effetto dei vaccini
- Rischio aumentato di “inflamm-aging”
(infiammazione di basso grado)
- Rischio aumentato di FGIDs
Da 60 anni in poi:
- Diminuzione dei bifidobatteri
- Aumento degli enterobatteri
36. Ceppo specifico con efficacia provata negli anziani
Bifidobacterium lactis HN019
TRANSITO INTESTINALE
SINTOMI GASTROINTESTINALI
Waller et al., Scand. J.
Gastroenterol., 2011
- Riduzione del tempo di transito
Effetto positivo sulla
regolarizzazione del transito
- Miglioramento dei sintomi
gastronintestinali es. dolore
adominale, meteorismo, movimenti
intestinali
1
IMMUNITÀ
Miller et al., Nutrients, 2017
3 Ahmed et al., J. Nutr., 2007
4 Gill, J of Clin Immunology 2001
2
- Incremento capacità fagocitica dei PMN
- Incremento attività tumoricida delle NK
- Incremento significativo della popolazione di
bifidobatteri
- Riduzione degli enterobatteri nocivi
- Efficacia dopo soltanto 2 settimane
- Incremento attività antitumorale dei linfociti e
monociti
- Incremento attività tumoricida delle NK
38. Current definition of probiotics refers to living and
vital orgnisms (no spore, no tindalized, no fragments).
Nuove ricerche sui filtrati sterili e sulla metabolomica
simbiontica aprono scenari futuri di prodotti
- Post-biotici (frammenti di organismi o metaboliti)
- Terapia con batteriofagi
- Terapia con mtaboliti fungini
41. Study shows:
1) The 2 strains together works better than the single strains
2) Efficacy (prevention) for 6 months treatment in healthy children
- Doppio cieco, controllato con placebo
- 326 bambini, Età 3-5 anni
- Durata dello studio 6 mesi
Pediatrics, Leyer G.J. et al, July 27, 2009;124;e172-e179
47. Ringel et al. Probiotic Bacteria lactobacillus acidophilus NCFM and Bifidobacterium lactis BI-
07 versus placebo for the symptoms of bloating in patients with functional bowel disorders –
a double blind study. J Clin Gastroenterology 2011;45(6):518-25.
3
4
5
6
7
Baseline 4 weeks 8 weeks
Active probiotic group
Placebo Group
P = 0.009 °
° Comparison between the groups at
each time point
Significantly less bloating after 4 and 8 wks
treatment with NCFM® and BI-07
N=60 (31 probiotics, 29 placebo)
Patients with FBD
Probiotics
48. Definition:
“A nondigestible food ingredient that
beneficially affects the host by selectively
stimulating the growth and/or activity of
one or a limited number of bacteria in the
colon, and thus improves host health”.
Gibson & Roberfroid. J NUtr 1995; 125:1401-12
Prebiotics
• Gibson, Roberfroid et al. Dietary modulation of the human colonic microbiota: updating
the concept of prebiotics. Nutr Res Rev 2004;17(2):259-75.
• Delzenne et al. Impact of inulin and oligofructose on gastrointestinal peptides.
Br J Nutr 2005;93:S157-61.
• Meyet et al. The bifidogenic effect of inulin and oligofructose and its consequences for gut
health. Eur J Clin Nutr 2009:63(11):1277-89.
50. Prebiotics
Roberfroid et al. Prebiotic effects : metabolic and health benefits. Br J
Nutr2010;104:suppl2:S1-63
• Stimulate the growth of beneficial bacteria
• Increase production of N-butyrate
• Modulate immunological biomarkers
• Improve the well-being of patients with IBD or IBS
• Possible role in the reduction of colon cancer
• Increase Calcium absorption
• Are dietary fibres
Inulin
& Oligofructose
52. MALABSORPTION
DEFICIENCIES
Priority micronutrients for DRV’s (Dietary reference values)
MINERALS
-Calcium
-Potassium
-Iron
-Zinc
-Iodine
-Manganese
-Copper
VITAMINS
-Folate
-Vitamin C
-Vitamin A
-Vitamin D
-Iodine
OTHERS
-Choline
SINU Congress 2013
EFSA Journal 2010; 8(3):1458 [30 pp.]. doi:10.2903/j.efsa.2010.1458
EURRECA/WHO Workshop report: “Deriving micronutrient recommendations: updating best practices”
53. Vitamin D
Prevalenza di carenza di Vitamina D in Italia (Anziani e giovani)
e confronto con altri paesi Europei. (1-3)
1) Adami “Linee Guida su prevenzione e trattamento dell’ipovitaminosi D con colecalciferolo” Reumatismo 2011
2) M. Gonzalez-Gross et al. British Journal of Nutrition (2012), 107, 755–764
3) Adami et al Bone 2008 & Isaia et al OI 2003
54. - SUVIMAX-study : number of people that does not reach the
A.R. for magnesium
‐ 77 % of women
‐ 72 % of men
Galan P et al. Dietary magnesium intake in a French adult population Magnes Res; 1997;10(4):321-8.
Magnesium
57. (1,2-dithiolane-3-pentanoic acid)
• Compound present in all body cells
• Converted into dihydrolipoic acid, also an AOX
• Alpha-lipoic acid and dihydrolipoic acid = strong AOX pair
• Water and fat soluble
• Recycle other antioxidants (vit C, vit E, glutathione, coQ10)
Alpha lipoic acid
Petersen et al. Alpha-lipoic acid as a dietary supplement : molecular mechanisms and
therapeutic potential. Biochim Biophys Acta 2009;1790(10):1149-60.
58. EGCG – Epi Gallo Catechin Gallate
(Green tea extract)
• Green tea : rich in catechins (polyphenols)
• EGCG : richest catechin
• Protects cells from lipid peroxidation and DNA damage
Polyphenols as an anti-oxidant and anti-inflammatory agent for CV protection. Tipoe et
al. Cardiovasc Hemat Disord Drug Targets 2007;7(2):135-44.
60. Curcumin
• Anti-inflammatory, anti-oxidant agent
• Principal curcuminoid of the turmeric
• EPIGENETIC MODULATION OF INFLAMMATION
BIO-OPTIMIZED FORMULATION
OF CURMUMINE AKA MICELLAR
CAN BE 1.350 TIMES MORE
BIOAVAILABLE
THAN CURCUMINE EXTRACTS
• Menon et al. Antioxidant and anti-inflammatory properties of curcumin. Adv Exp
Med Biol. 2007;595:105-25
• Jurenka J et al. Anti-inflammatory properties of curcumin, a major constituent of
curcuma longa : a review of preclinical & clinical research : Altern Med Rev
2009;14(2):141-53.
Cell membrane
Arachidonic acid
Prostaglandins
Inflammation
Inflammation
PLA2
COX2
PLA2
COX2Curcumin
NF-kB
61. Is it possible to combine those active
ingredients into one single formula?
• L-glutamine : since years used for GI function in patients with IBS, IBD, after surgery,
cancertherapy, radiotherapy,...
• Probiotics : > Safe and effective strains with strong evidence of supprting GI health
• Prebiotics : > mix of FOS and Inuline
• Anti-oxidants : 2 highly published anti-oxidants
• Anti inflammatory agent: bio-optimized curcumin and/or Boswellic acids
• Vitamines in active forms
• Minerals in bioavailable forms
63. 28 patients carried out the second
measurement of permeability.
Average 51CrEDTA score was
7,43 (SD: ±2,75) at start
5,93 (SD: ± 2,7333) after treatment
(P=0.089).
Average value EQ-5D VAS was
40.0 (SD: ±14,86) at start
64.6 (SD: ± 9) after treatment (P<0.0001).
+61.5%
Trend
diminuzione
“A multimodal approach, with a combination of different agents
with a therapeutic action, seems to be effective both in improving
intestinal permeability and in improving symptoms”
INTESTINAL PERMEABILITY Cr-EDTA SYMTOMS- EQ-5D VAS
A multimodal approach, with a combination of different agents with a therapeutic action, seems to be effective both in improving intestinal permeab
64. 50 athletes
705 athletes at start (7%)
47 athletes trained their gut for 1 month before the
competition
End of training
Athletes used micronutrition foormula during the competition
together with regular meals
The study:
FORM 1
N=47
FORM 2
N=47
FORM 3
N=41
65. RESULTS:
• 24 athlets/47 report 1 or more benefit linked to the treatment (51 %)
during training and copetition
GENERAL AND GI BENEFITS
• 11 Athletes report more energy and resistence (23,4%)
MORE ENERGY AND RESISTENCE
• 1 /42 athlet drop-out from the treatment group (2,3%)
• 6/50 atlets drop-out from the control group for GI reasons)
5 TIME LESS DROP-OUT FOOR GI PROBLEMS IN TREATMENT GROUP
DROP-OUT FOR GI REASON DURING COMPETITION
66. • High salt consumption -> Th17 (pro-inflammatory cells)
• Vitamin deficiency A -> alterations of commensal microbial flora;
variation in the expression of MUC2 and defensin 6 proteins (changes
in the mucosal layer and reduction in anti-microbial peptides);
• Vitamin deficiency D -> greater susceptibility to epithelium,
decreased Treg cells
• Zinc deficiency -> alterations of ZO-1 protein expression, occludine
and F-actin
• Food additives -> interference with tight junctions protein/mucus
• Alcohol -> altered distribution of ZO-1 and occludin proteins
Impact of Nutrition on GI Barrier
67. • EPA and DHA -> promote the synthesis of ZO-1 and occludin-1
proteins, epigenetic modulation of inflammatory cytokines (IL-6, TNF-α)
• Vitamin D -> promotes the synthesis of ZO-1 and Claudina-1 (tight
junctions) and E-cadherin (adherent junctions) proteins
• Flavonoids (quercetin, miricetin, canferol) -> increase of claudin-4
protein expression and assembly of ZO-2, occludine and claudin-1
proteins in tight junctions
Impact of Nutrition on GI Barrier
68. • Caloric intake should fullfill energetic needs
• Protein intake should be from 0,60 to 1,25 grams/kg/12 Hours
• Water Na, K, Mg, Cl intake should be monitored and adapted
• Diet should provide 25-30g fibers/day better if soluble fibers
• Vitamins, minerals, essential AA intake should be monitored and
supplemented if needed
• Plant based diets aka MEDITERRANEAN or evolutionary diet provides
a lot of anti-oxidants, epigenetic modulators
• Diet should respect as much as possible chronobiologic rithms
• Training sessions should respect digestion time needs
• Alcol and stimulants should be avoided
(caffeine ok only for fast metabolizers)
• Supplementation should be monitored and personalized by HCP
• Attention to pain killers, NSAIDs, IPP that can disrupt gut barrier
REAL FOOD ONLY – NO JUNK OR SHIT FOOD
69. • GI Health is a pillar for general health AND performance in
athletes
• Sport can be both helpful AND detrimental for GI health
• Intense and prolonged effort promote alterations of
gastrointestinal barrier
• Strategic micronutritional and dietary interventions can
train the gut to better withstand acute and sport linked
acute and chronic stress
• Med diet as well as other balanced appropriate diet based
on REAL FOOD is the best choice for GI in athlets
• Quality of micronutrients and bioactive substances is
important and we should always choose bio-active and
bioavailable micronutrients
70. Contatti: msal37@gmail.com +39 3663461468
https://www.linkedin.com/in/mauriziosalamone
http://www.slideshare.net/Maurizio37
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Maurizio Salamone, biologo
Direttore Scientifico - Metagenics Italia srl.
Società Internazionale di Neuropsicocardiologia
Disclaimer:
Maurizio Salamone is employe of Metagenics Italia srl