Personalised nutrition, Michael Gusko, ICC Conference, Vienna, 24-APR-2019

www.goodmillsinnovation.com
SHAPING THE FUTURE OF NUTRITION:
THE CASE OF PERSONALISED NUTRITION
19th ICC Conference 2019, SCIENCE MEETS TECHNOLOGY
Michael Gusko
Vienna, Austria, 24-APR-2019

Subject GI
1 42.8
2 61.5
3 59.4
4 143.0
5 42.8
6 50.5
7 40.3
8 84.5
9 39.0
10 37.1
Mean 60.1
In 2004 we launched ‘GLYX Ideal Diet Bread’ - a premix for
a low GI bread (GI 38, GL 6, TDF 10g)
Shaping the future of nutrition: The case of personalized nutrition | 19th ICC Conference – Science meets technology | Vienna, Austria | 24-APR-2019 2
Randomly selected test results from the series of studies during the product
development phase → high interindividual variations in glycaemic response.
GI of bread
Advertising poster for bakeries. GLYX is the acronym of ‘GLYcemic Index’; it’s phonetically similar to the German word “luck” or “lucky”.
THE DAY MY
INNOCENCE
DIED!
Data sheet of
the medical
university of
31-OCT-2002

THE FLAW OF AVERAGES: REAL LIFE IS NEVER AVERAGE!
The average advice is
fine if you’re average.

THE MOST IMPORTANT RESOURCE FOR HEALTH
19th century:
CLEAN WATER
21st century:
CLEAN KNOWLEDGE
Statement: Günther Jonitz, President of the Berlin Medical Association, 2018

5
We must, however, take an honest look at ourselves as well
Allen Roses, worldwide vice-president
of genetics at GlaxoSmithKline (GSK),
London, 2012
Shaping the future of nutrition: The case of personalized nutrition | 19th ICC Conference – Science meets technology | Vienna, Austria | 24-APR-2019
”OUR DRUGS DO NOT WORK ON MOST PATIENTS.”

6
“Fewer than half of the patients prescribed some of the most
expensive drugs actually derived any benefit from them.”
GSK figures on how well different classes of
drugs work in real patients:
• Depression 62%
• Asthma 60%
• Diabetes mellitus 57%
• Migraine, osteoporosis, and arthritis 50%
• Alzheimer‘s disease 30%
• Cancer 25%
Source: Allen Roses, GlaxoSmithKline (GSK), London, 2012
Allen Roses, GSK, London, 2012

7
“Most drugs work in fewer than one in two patients
mainly because the recipients carry genes that interfere
in some way with the medicine.”
Allen Roses, GSK, 2012

PRECISION MEDICINE: PHARMA USES “BIG DATA”
APPROACH TO TARGETED PRECISION DRUGS
Adapted from Eric Topol, Individualized Medicine from Prewomb to Tomb, Cell (2014): 157(1), 241-253
Input
Layer
Hidden
Layer 1
Output
Layer
Hidden
Layer 2
1. Deep
Phenotyping
2. Deep
Learning (AI)
3. Deep
Empathy and Connection
Ability to deeply define each individual
(digitizing the medical essence of a human being)
Deep learning AI is all about inputs and outputs:
Pattern recognition and machine learning is a
new superpower
After decades of degradation of the human side
of medicine → Comeback of deep empathy and
connection between patients and clinicians
The three components of the deep medicine model according to Eric Topol

The Fourth Industrial Revolution is here: How can food
and nutrition be a part of this change?
connectivity
1st Industrial Revolution
MECHANICAL, water and steam power
Age of machine aided production
Power generation and mechanical
automation empowers industrial processes
2nd Industrial Revolution
ELECTRICAL: Mass production, assembly line
Age of mass production
Division of work, global connections and
transportation systems
1830 1910 1990 2010
3rd Industrial Revolution
INTERNET: IT automates production
Age of electronic automation
Use of electronic and IT systems that further
automate production, internet technology
Shareholder value Capitalism
Firms should maximize shareholders’ wealth
4th Industrial Revolution
DIGITAL: Cyber-physical systems
Age of smart connectivity
Internet of Things (IoT),Artificial Intelligence
(AI), big data, cloud, empowered customers
Customer driven Capitalism
Firms focus on creating customer value
Managerial Capitalism
Firms require professional management

PERSONALIZED FOODS AND DRUGS: WHY NOW?
New technologies and algorithms are making the individualization strategy more viable today
10Shaping the future of nutrition: The case of personalized nutrition | 19th ICC Conference – Science meets technology | Vienna, Austria | 24-APR-2019
Fitness tracker Nutrition AppsMachine learningDNA & Microbiome testing Big data & Data mining

MEDICINE: WISDOM OF THE PAST AND ITS
TRANSMISSION INTO THE FUTURE
“If the pattern of the heart beat becomes as
regular as the tapping of a woodpecker or
the dripping of rain from the roof, the
patient will be dead in four days.”
Chinese physician Shu-He Wang (265–317 AD)
300 AD
After the morning toilet you get a call:
“At 11:40 in the morning, you’ll have a heart attack. Don’t worry.
Please come to the Holistic Health Center after breakfast.
We’ll solve the problem right away.”
2025 AD
FDA clears AliveCor’s Kardia-
band in 2017 as a medical
device for the Apple Watch to
detect atrial fibrillation
AliveCor clinician-facing app
using artificial intelligence
(AI) to pick up signs of atrial
fibrillation earlier

New gadget can detect early signs of heart failure by picking
up blood pressure, oxygen levels and heart rate (2019)
A team from Rochester Institute of Technology has developed a toilet seat
that can measure a host of important cardiovascular parameters while the
patient is using it. The new toilet seat measures diastolic and systolic
blood pressures, stroke volume, blood oxygenation, heart rate, heart rate
variability, QRS duration, and corrected QT interval. The patient is also
weighed, though that would require lifting the feet off the ground.
https://www.medgadget.com/2019/02/toilet-seat-automatically-measures-host-of-cardiac-parameters-to-monitor-heart-health.html

Big tech pushes into wellness: Apple Watch can detect early
signs of diabetes + supporting diabetes management
Apple CEO Tim Cook has been spotted testing a glucose monitor prototype which was connected
to his Apple Watch to understand how his blood sugar is affected by food and exercise.
2017

Tufts University, 2018: Tooth-mounted sensors track
your diet and health from inside your mouth

NUTRITION: WISDOM OF THE PAST AND ITS
TRANSMISSION INTO THE FUTURE
“Let food be thy medicine
and medicine be thy food.”
Hippocrates of Kos (460–370 BC)
300 AD
In 2030, the metabolism of each human being is decoded and we
can quantify to the minute how a food or drink affects our lifetime.
2030 AD
„The drug we all take multiple times a day that needs to
be personalized most is food.“ Lisa Pettigrew, 2017

Postprandial blood glucose (PPBG) regulation is
crucial for the development of metabolic diseases
Credit: Ted Naiman Glycemic index, glycemic load and glycemic response: An International Scientific
Consensus Summit from the International Carbohydrate Quality Consortium
(ICQC), Nutrition Metabolism and Cardiovascular Diseases, May 2015

17
Zeevi et al., Cell, 2015
Breakthrough study, 2015: Personalized Nutrition – proof
of concept study (Eran Segal, Eran Elinav, Weizman Inst.)
A close examination of all the factors that enabled us to predict each person’s individual response showed that one of the most significant of
them was the microbe population. We discovered that each person has a distinctive cocktail of microbes, a kind of characteristic
signature, which affects his responses to food.

The body's reaction to food is a very personal matter
http://dx.doi.org/10.1016/j.cell.2015.11.001
The food constituents weren‘t
the driver for glucose response.
The bacterial species in the gut
microbiome proved to be the
key determinant of each person‘s
glucose response to eating.
KEY FINDING:
“Because our data set was so
large and our analysis so
comprehensive, these results have
an enormous impact – they show
more conclusively than has ever
been shown before that a generic,
universal approach to nutrition
simply cannot work.”
Segal and Elinav, The Personalized Diet, 2017

Bread intervention study: Comparing the effect of white
bread and sourdough bread (e.g. postmeal blood sugar)
Eran Segal and Eran Elinav, The Personalized Diet, 2017
White Bread Sourdough Bread
OR
• „Whole-grain” sourdough bread (“sifted the flour to
remove only the largest bran particles”)
• Ingredients: Stone milled fresh hard red wheat,
water, salt, and a mature sourdough starter
• Diet: 5 ounces (= 142 g) of sourdough bread every
morning (= 50 grams of available carbohydrates)
• Industrially produced white bread (Israel)
• 100% wheat flour
• Yeast-risen
• Diet: 4 ounces (113 g) of white bread every
morning (= 50 grams of available carbohydrates)

Glucose response to bread is highly personalized →
no universal dietary rule can possibly apply to all people
Korem & Zeevi et al., 2017
LEFT GRAPH:
Example of two participants in the
bread intervention study:
• The top participant responds
more highly to sourdough bread
• The lower participant responds
more highly to white bread
• The reactions were essentially
opposite
RIGHT GRAPH:
• Differences between the average
PPGR to white and sourdough bread.
• Some people had quite modest blood
sugar rises after eating bread, while
others had larger spikes.
• In term of blood sugar spikes big
differences between breads.
iAUC: Incremental area under the curve from
fasting to at least 120 minutes after consumption
PPGR: Postprandial Glycemic Response

Different people have widely different post-meal
responses to the same standardized meal
Zeevi et al., Cell 2015 PPGRs = postprandial glycaemic responses
Example of high interpersonal variability
and low intra-personal variability in the
PPGR to bread across four participants
(two replicates per participant consumed
on two different mornings).

Glucose response of different foods and drinks
(taken as an individual meal)
AUC: Area under the curve iMF: intermittent fasting Each dot represents the glucose response (tissue) of a single person
Glucoseresponse(AUCiMF)
C. Sina, 2018, NEWTRITION X. conference

Breakthrough in dieting science: Gut bacteria are
behind relapsing obesity (monozygotic twin study)
Ridaura VK. et al. Science 2013
It has long been
a frustrating mystery
why some people ...
… while others just look at
a potato and put on weight.
eat a lot and
still stay slim, ...

Transplantation of the microbiota of two twins into
normal weight mice
Treatment of obesity and the associated metabolic syndrome:
Modulation of the intestinal microbiome could be a weapon against obesity
Result: Insulin sensitivity was transferred
from the donor to the recipient!
Ridaura VK. Et al. Science 2013

The multiple hit hypotheses for how microbiota has
lost diversity over time
•MAC: microbiota-accessible
carbohydrates
(remark: cellulose is not
fermentable)
•MAP: microbiota-accessible
phytonutrients
Source: Modified after Sonnenburg
and Sonnenburg, Cell, 2014
100-150 g fiber/d
bitter fruits/veg.
15-20 g fiber/d
sweet fruits/veg.
35 g fiber/d
mild fruits/veg.

Gut bacteria feeds on fiber. A starving microbiota
eats you (mucus layer) → “leaky gut”
Fiber-rich diet Fiber-deficient diet
Earle et al., Cell Host
Microbe, 2015
(Green) mucus layer
on a high-fiber diet
pushing away the
(red) microbes from
the (blue) intestinal
cells) → keeps us
safe from infection
(Yellow) plant cell
wall material (fiber
= food for the
microbes)
Microscopic image,
mouse model with a
human microbiota (colon)
(Red) microbes starve
and start eating the
mucus layer (which is
made of carbohy-
drates, back-up food
source for microbes if
they don’t have
anything to eat)
Microbes move closer
to the intestinal cells
→ and start an inflam-
matory response
(Green) mucus layer
thins (starves)
one month later

Rewilding the microbiota with High-MAC wholegrain
flour: Bran/germ micronized (<150 µm) + heat treated
Standard
Refined wheat flour
Type 405
THE „BAD“
White
Fine texture
Low fiber
Standard (Red Wheat)
Wholegrain flour
1st generation
THE „UGLY“
Reddish
Rough texture
High fiber
Micronized White W.**
Wholegrain flour
4th generation
High-MAC
Light brown
Fine texture
High-MAC fiber
White Wheat*
Wholegrain flour
2nd generation
Light brown
Medium texture
High fiber
THE „GOOD“
Modulation of the microbiome:
“The two wheat bran fractions (1690
µm versus 150 µm) differently
affected specific gut bacteria
known to be involved in the
regulation of the gut barrier
function and/or inflammatory
processes.
Moreover, wheat bran with small
particle size was the sole fibre that
reduced hepatic and systemic
inflammatory markers upon high
fructose intake.
The anti-inflammatory effects of
wheat bran may be dependent on
their particle size and could be
related to the changes in caecal
Enterobacteriaceae.”
Suriano et al: Journal of Func-
tional Foods 41 (2018) 155-162
Note: 3rd generation of wholegrain flour is
a fermented wholegrain flour, Carat®
(EU HealthBread project)
* Snow Wheat® ** White Gold®

Ancient peach and today‘s modern peach: bigger,
sweeter, juicier
https://jameskennedymonash.files.wordpress.com/2014/07/artificial-natural-peach2.png
ANCIENT PEACH, 4000 B.C. TODAY‘S PEACH, 2014

Our microbiota is an „unsupervised drug factory“
“We used to think that drugs were
developed by drug companies,
approved by the FDA, and
prescribed by physicians,
but we now think there are
many drugs of equal potency
and specificity being produced
by the human microbiota.”
Michael Fischbach, UCSF
A team led by UCSF microbiome
expert Michael Fischbach
identified more than 3,000
clusters of bacterial genes at
different body sites that contain
the blueprints for cellular
factories that make drug-like
molecules.
Michael Fischbach, UCSF, on identifying & characterizing functional significance of metabolites produced by microbiome

Continuous glucose monitoring
Using a subcutaneous sensor (Abbott FreeStyle Libre)
Diary (food, sleep, physical activity
Using smartphone-adjusted App (Food Database)
Standardized meals (50g available carbohydrates)
Per person profiling
…
… Day 14
Three dietary intervention studies with Tartary buckwheat:
Blood sugar response (2017, 2018, 2019)
Prof. Dr. med. Christian Sina
Universität zu Lübeck, Germany
Test subjects (100, 20, 160 people)
(Glucose response)
Microbiome analysis
(+ Metabolome, ...)
High-MAP quality
(Rutin encapsulated, …)
…
2017: Data-mining for natural ingredients with bioactive properties,
2018: dose-response relationship, 2019: modulation of the microbiome

Day 8
60g
glucose
185 mg/dl
STUDY 1: Blood sugar  115 mg/dl, variance 45 – 185 mg/dl
my max. glucose level
(glucose test meal)
185
High-MAC and High-MAP diet: Modulation of the micro-
biome and blood sugar response
Day 12 → much lower blood sugar
135 mg/dl
60g
glucose
Seven months later:
60g
glucose
145 mg/dl
(glucose test meal)
145
Day 8
Day 14
85 mg/dl
60g
glucose
hereafter: High-MAC
and High-MAP diet
hereafter:
High-MAP diet

Day 8
60g
glucose
185 mg/dl
hereafter: High-MAC
and High-MAP diet
(glucose test meal)
185
High-MAC and High-MAP diet: Modulation of the micro-
biome and blood sugar response
Day 12 → much lower blood sugar
135 mg/dl
60g
glucose
Seven months later:
60g
glucose
145 mg/dl
(glucose test meal)
145
Day 8
Day 14
85 mg/dl
60g
glucose
INSIGHT
With a High-MAC and High-MAP diet I (!) could reduce my (!)
personal blood sugar reaction significantly. Blood sugar
increase after consumption of glucose much lower than before.
hereafter:
High-MAP diet

History is being repeated: The established world view
is on shaky ground
Church Inquisition Court, Rome, 1633
HEALTHY EATING PYRAMIDS ON TRIAL
1992 2005
RELIGIOUS BELIEF ON TRIAL
• Galileo’s championing of the heliocentric view - overturning the
geocentric model - was opposed by the Catholic church.
• Galileo’s trial is often referred to being the classical fight
science-versus-religious belief.
• 1992: After 350 years, Vatican says Galileo was right and the
“infallible” pope was wrong.
“This indeed is the biggest problem facing nutrition guidelines –
the idea that there is a simple one diet that all human beings should
follow. The idea is both biologically and physiologically implausible,
contradicting our uniqueness, the remarkable heterogeneity and
individuality of our metabolism, microbiome, environment, to name a
few dimensions.” Eric Topol, in: Deep Medicine, 2019
Food Guide Pyramids, U.S. Department of Agriculture (USDA)

Nutrition experts need to dive into the world of ‘smart connectivity’
if they want to have a real impact on nutrition in the future.
The rate that tech is evolving to influence nutrition is fascinating and ‘scary’ at the same time:
Algorithms of health apps are calculating a “health score” of the individual’s food & drinks.

Thank you for
your attention!
GoodMills Innovation GmbH
Trettaustrasse 35
21107 Hamburg, GERMANY
michael.gusko@goodmillsinnovation.com
T +49 40 75109-666 F -680
CONFIDENTIAL
This document contains confidential information of GoodMills Innovation GmbH, and
may not be disclosed to anyone other than those to whom it was originally distributed.
© GoodMills Innovation GmbH, Hamburg, Germany 891 until 2019

Personalised nutrition, Michael Gusko, ICC Conference, Vienna, 24-APR-2019

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