Carbohydrate Availability PDF

Xinova is looking for your invention
REQUEST FOR INVENTION (RFI)
Carbohydrate Availability and

Utilization Measurement
Key words: Carbohydrates, Carbohydrate Metabolism, Glucose, Glycogen, Carbohydrate
Availability, Carbohydrate Utilization, Athlete Performance
Circulation Date: Request for Invention

March 6, 2017 RFI-170103
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Xinova PROPRIETARY AND CONFIDENTIAL INFORMATION

REQUEST FOR INVENTION Nutrition // RFI-170103
Carbohydrate Availability and Utilization Measurement
SUMMARY
Xinova is seeking non-invasive, portable methods to measure physiological

carbohydrate availability and utilization in the body before, during and
after physical activity.
Sports performance is impacted by the nutrition of the athlete. Critical to

performance is the availability of carbohydrates and the rate at which the athlete is
utilizing them. Information regarding carbohydrate availability and utilization rates
could provide athletes the information necessary to positively impact their
performance during training and competition. This data will allow for intervention
before, during and/or after exercise based on carbohydrate availability and
utilization rates from a series of monitoring periods collected over time.
Desired invention characteristics and some suggested areas of exploration

are described on page 8.
RFI Partnership
This Request for Invention (RFI) is sponsored by PepsiCo. As one of the largest food
and beverage companies in the world, PepsiCo’s mission is to provide consumers
around the world with delicious, affordable, convenient and complementary foods
and beverages from wholesome breakfasts to healthy and fun daytime snacks to
evening treats.
PepsiCo centers its strategy and operations on the theme of Performance with
Purpose – aligning what is good for their business with what is good for society and
the planet. It starts with what they make – a wide range of foods and beverages
from the indulgent to the more nutritious; extends to how they make their products
– conserving precious natural resources and fostering environmental responsibility
in and beyond their operations, and considers those who make them – striving to
support communities where they work and the careers of generations of talented
PepsiCo employees.
Xinova PROPRIETARY AND CONFIDENTIAL INFORMATION 2

Problem Definition
All forms of digestible carbohydrates are eventually broken down to glucose, the
simplest carbohydrate. Often, the body stores glucose as glycogen, a chain of
connected glucose molecules. For the purposes of this document, the term
carbohydrate will mean glucose and glycogen.
Carbohydrates are the body’s preferred fuel to sustain the muscle activity during
more intense exercise or activity because they are metabolized quicker than fats.
Carbohydrate availability is a measure of the amount of blood glucose and
glycogen stored in the muscles (and liver), as the total carbohydrate accessible.
Carbohydrate utilization, or the conversion of blood glucose and muscle glycogen
to pyruvate and lactic acid, takes place to produce more adenosine triphosphate
(ATP), which allows the muscle cells to contract.
Measuring carbohydrate availability is typically done invasively and requires
laboratory instrumentation. Likewise, measuring carbohydrate utilization is
typically done in a lab setting through repeated blood sampling and breath
monitoring for oxygen and carbon dioxide concentrations. Thus, it is not possible to
discern an athlete’s carbohydrate availability and utilization in real-time via a
practical field-based method.
Xinova is seeking non-invasive, portable methods to measure physiological
carbohydrate availability and utilization in the body before, during, and
after physical activity in real-time (or close to it).

Background
Adenosine Triphosphate (ATP)
During physical activity, exercise, or sports the body needs energy to perform.
Initially, the body draws upon compounds containing energy which are stored in the
body as adenosine triphosphate (ATP) or creatine phosphate. Energy released by
the breakdown of ATP enables muscle cells to contract. However, as these
compounds in storage run out, the body needs to replenish them. Fats and
carbohydrates are the primary energy sources for the body to enable sustained
muscle function beyond the initial utilization of stored reserves of ATP and creatine
phosphate. Fats are metabolized slower than carbohydrates and are the ideal fuel
during longer duration or lower intensity workouts. The more intense the activity,
the more the body relies on carbohydrates for energy.
Anaerobic vs Aerobic Metabolism
The metabolism of carbohydrates can be anaerobic or aerobic depending on the
athlete’s exertion level. Anaerobic carbohydrate metabolism, or anaerobic
glycolysis, is a breakdown of glucose without the need for oxygen. This metabolic
energy pathway kicks in under high intense activity where there is not enough
oxygen to supply the muscles with the energy they need and is usually only
sustained for several minutes.
Aerobic metabolism fuels the body with most of its energy need for a longer
duration of time, where oxygen helps convert glucose to ATP. In either case,
during high bursts of activity or longer endurance activity, carbohydrate utilization
is a key component to athletic performance.
Other aspects of human physiology and glucose metabolism are discussed in

Appendix A.
Why This Problem Is Valuable to Solve
Professional and collegiate sports teams could gain a competitive advantage by

being able to monitor carbohydrates not only during competition, but also during
training. They would find such technology extremely valuable. In addition, tens of
millions of consumers would be interested for their personal use. For example,
FitBit, maker of wearable activity trackers for consumers, generated USD$1.9B for
fiscal year 2015. Besides athletics, this technology could be used in the healthcare
field.

Current Technology and Prior Solution Attempts
Carbohydrate Availability
Blood glucose measurement
Blood glucose concentration is the amount of glucose present in the blood and is
tightly regulated by the body through metabolic homeostasis. Glucose is the
primary source of energy for the cells and is transported from the intestines or liver
to the other cells of the body through the bloodstream. Glucose is made available
for cell absorption by insulin. Blood-glucose monitoring is the typical test to
determine the concentration of glucose in the blood, usually performed by a simple
needle stick to generate a single drop of blood. Many non-invasive technologies are
being developed that do not require a blood test but are based on patterns of light,
ultrasonic methods, electromagnetics, and thermal patterns. As a standalone
measure, blood glucose concentrations tell us little about carbohydrate availability,
unless concentrations stay low for a prolonged period of time.
Muscle biopsy for glycogen concentrations
Although muscle biopsy is the most common way to measure glycogen stores, this
is extremely invasive and other methods are in development. NMR has been used
to non-invasively measure brain glycogen in humans (Oz et al. 2013). However,
this and other similar methods in development are theoretical laboratory studies.
Carbohydrate Utilization
In order to get an accurate picture of carbohydrate utilization, many parameters of

metabolism must be considered. These parameters include blood glucose, lactate
metabolism, fat metabolism, VO2 max, metabolic efficiency and carbohydrate
metabolism.
Exercise physiology laboratory (O2, CO2, water, weight, controlled

environment, etc.)
Some of the different metabolic parameters that are measured in the controlled
setting of an exercise physiology laboratory include plasma glucose, oxygen
utilization, carbon dioxide production, heart rate, breathing rate, depth of
breathing, dehydration, and lactate threshold. Technologies to study exercise
physiology include ergometers with bicycles and treadmills, accelerometers, heart
rate monitors, and combined heart rate monitors and accelerometers.
Tracer studies (e.g. isotopic labels)


Stable isotope tracers have been used in physiological research for over eight
decades and allow insight into amino acid, fatty-acid and carbohydrate metabolism.
Although these studies have been useful in gathering physiological information,
these studies are restricted to short-term studies (hours) in laboratory settings.
Recently, technological development has focused on alternative stable isotope

tracer techniques to overcome these limitations. Heavy water, or D2O, is one
approach that has been explored. Stable isotopes can be used to study protein
metabolism using 13C phenylalanine, carbohydrate metabolism using 2H glucose,
and fat metabolism with 13C palmitate. Other tracers being developed include
orally administered d3-methylhistidine and d3-creatine to determine muscle protein
breakdown and whole body muscle mass without imaging. Both of these
technologies are minimally invasive since measurement can be performed on urine
samples.
Hormone monitoring (insulin/glucagon levels, others)

There are multiple tests that are currently available for monitoring hormones, which
can give an indication of carbohydrate utilization. Body fluids such as blood, saliva,
sweat, and urine can be used for testing and each has advantages depending on
what hormone is being measured. Urine is non-invasive and is not as prone to the
hour-to-hour fluctuations seen in saliva and blood. Urine is a stable indicator and a
reliable way to assess physiological hormones such as estrogen metabolites, and
other female and male hormones. Blood is used to measure circulating hormones
such as insulin and endocrine activity. Collection is obviously more invasive due to
the necessary needle stick to obtain the sample. Glucose meters revolutionized
diabetes therapy, however a blood sample is still required. This is an important
example of improvements in measuring a metabolic parameter. Before the advent
of glucose measuring, patients had to perform a “chemistry experiment” with their
urine. Saliva, which is also collected in a non-invasive manner, can be used to
measure circadian regulated cortisol levels and for menstrual cycle evaluation.
Current technological trends for measuring hormones in the laboratory include

multiplex panels using protein or antibody arrays or chips. Single plex methods
may also be used such as immunoassays including ELISA and RIA (radio-
immunoassays). Gas chromatography (GC)- mass spectrometry (MS) and Liquid-
Chromatography (LC)-MS/MS are also widely used to measure the pico- and
nanomolar concentrations of hormones in the human body. However, these
laboratory techniques all take hours, if not days, to perform.
Emerging technologies include a wearable sensor that is being developed to

measure the hormone cortisol in sweat to determine stress levels. Another
emerging technology is the Cue (cue.me/product) which can measure fertility


(luteinizing hormone) and testosterone from blood or saliva, respectively, using a
small tracking cartridge and a smart phone application.
Metabolic control analysis (e.g. Seahorse for cellular studies)

Metabolic control analysis (MCA) is the quantitative measurement of the flux of
metabolite concentrations. MCA can be used to understand the biochemical
networks in cellular systems. In MCA, mathematical frameworks are used to
describe metabolic, signaling, and genetic pathways and this allows for a
comprehensive approach to studying metabolism as opposed to examining a single
enzymatic pathway. The Seahorse XF Analyzer is an example of a technology that
measures cellular bioenergetics using oxygen consumption rate and extracellular
acidification rate which are indicators of mitochondrial respiration and glycolysis,
respectively. Using the Seahorse XF, these pathways are measured in real-time in
live cells.
Other Non-laboratory methods (wearables, portable measures, etc.)

A new method has been developed to determine muscle glycogen content through
imagery using high frequency ultrasound. However, this is the only method that
appears to directly measure glycogen stores (carbohydrate availability). There are
other methods and devices that aim to measure other aspects of metabolism during
exercise but these involve a more indirect approach such as lactic acid and caloric
burn.
Other approaches include measuring electrical signals in muscle to determine

fatigue. Most of the aforementioned technologies do not directly address
carbohydrate availability or utilization with the exception of the ultrasound
technique which more closely targets the problem.

Invention Suggestions
Solution Characteristics
 Measurement of carbohydrate availability and utilization in real time during

athletic activity, continuously over time and/or quickly during a break from
play on the sideline:
o Continuous monitoring in-field or during performance
o Quick measurement during a break in performance (ideally <60 seconds)
 Target users are high performance athletes as well as mainstream consumers
 Data acquisition should be non-invasive and could include wearables on the

body. The device should fit with existing sporting equipment, or other means
to derive data that can be taken on and off the body during rest
o Means for acquiring data should be portable
o Means of acquiring data for data collection can be wireless or manual
 Insulations whose properties can be controlled either at system level or

material level (e.g. airgels that can be inflated/deflated)
 Cost should skew toward scalability or could be at cost for targeted use with
performance athletes
Out of scope
 Invasive, diagnostic equipment or device
 Biopsies and other surgical methods

Current Market Review
Currently, there is high demand for technologically advanced products which is

expected to drive growth of the smart fitness wear market. The smart fitness wear
market is projected to grow at a CAGR of more than 30% from 2016 to 2024. This
growth will be influenced by rising awareness of physical fitness; increasing
demands for items such as smart watches, smart wristbands, fitness/activity
trackers, and smart clothing; and increased use of these products by athletes and
trainers. The US market is expected to be the most lucrative regional market for
such devices. However, Asia Pacific will experience significant growth while Europe
will exhibit moderate growth.
More specifically, the sports and fitness performance wearables market is projected
to reach $14.9 billion by 2021. This market includes the measurements of
biometrics and analysis of joints, muscles, heart rate, respiration, cadence, and
endurance parameters, similar to products in the smart fitness wear market.
Examples of end applications for wearable sports technologies include sports
watches, embedded sports equipment, and smart clothing:
https://www.maximintegrated.com/content/dam/files/design/technical-documents/white-papers/wearable-sports-
technology.pdf

The body sensors market is another relevant market for the invention. This market
includes health patches, skin sensors, flexible energy-harvesting sensors, and
implantable sensors. The leading segment of end users in the market is
sports/athletes. This market is closely related to smart clothing, wearable
garments that can be used to measure certain aspects or activities of the body.
The sensors are built into or woven into the fabric of the garment alleviating most
skin irritations that could be caused by skin contact with devices. There are many
applications for these sensors including sports and fitness. Smart clothing is
projected to reach $603 million by 2020.
Competitive Landscape
There are many companies within the competitive landscape that are developing
technologies for improved metabolic sensing. A direct competitor to the currently
proposed invention is MuscleSound, who has developed a non-invasive way to
image muscle glycogen using ultrasound. The system includes software to read the
ultrasound images. The MuscleSound technology is proprietary and appears to be
on the market as of 2016 (https://www.musclesound.com/product/glycogen/).
BSXinsight is a wearable device the measures lactic acid in the calf. The device is
contained within a compression sleeve worn on the calf and uses LED light to
measure aerobic and anaerobic fitness. The LED light array passes through the
muscle, is reshaped by chromophores of the tissue creating a biosignal that is
captured and analyzed by BSX algorithms to generate a profile. A real-time lactate
threshold curve is generated that it claimed to be as accurate as blood-based
methods (https://www.bsxinsight.com/technology).
The LEO is a more comprehensive approach that measures an array of biosignals.

This technology, which is currently being crowd-funded for development, is based
on the use of electromyography or the process of acquiring small electrical signals
generated by muscle contractions at the surface of the skin. The device and
algorithms measure muscle intensity and fatigue, balance, muscle coordination,
hydration, muscle targeting, technique analysis, efficiency, and lactic acid
(http://leohelps.com/#!/meet-leo). Although the LEO uses biosignals from EMG to
measure important and relevant aspects of metabolism during physical activity such
as lactic acid levels and muscle signatures, the device does not offer a direct
measurement of carbohydrate utilization.


Another comprehensive measurement system in development is the GoBe, a
wearable device that takes measurement through the skin to track calories
consumed and burned, activity, hydration, sleep, and stress levels
(https://www.indiegogo.com/projects/healbe-gobe-the-only-way-to-automatically-
measure-calorie-intake#/). This technology uses a pressure sensor, an impedance
sensor and an accelerometer. Somaxis has also developed Cricket which is a
wearable sensor for muscle, brain, posture, and movement
(http://www.somaxis.com/). This product appears to fit into the physical therapy
space for wearable sensors, therefore is an indirect competitor since there is no
measurement of carbohydrate utilization.
A major market competitor is Philips. Philips has developed optical biometric
sensing in a wrist-worn or head-mounted device. The optical sensor tracks blood
volume variations and includes an accelerometer to track body motion and
algorithms to process the data from the sensor
(http://www.usa.philips.com/healthcare/sites/wearable-sensing-technologies).
However, this product is not in direct competition. Some wearable sensing metrics
that are in development include measurement of respiration rate, and energy
expenditure.
LifeWave Biomedical has developed a single, small, wireless, and wearable device
that measures respiration rate, rhythm, and estimation ventilation, and claims to be
able to determine anaerobic threshold (http://www.lifewavebiomed.com/Athletics).
LifeWave uses microwave radiofrequency technologies to develop internal organ
tissue assessment devices with real-time monitoring. However, the applications for
their products currently appear to be medical as opposed to exercise physiology or
fitness-related.

Potential Markets and Applications
Some other relevant markets for a carbohydrate sensor include medical sensors
with applications for diabetes. This is a multi-billion-dollar market and there is an
unmet need for non-invasive technologies that do not include a needle stick to test
for blood glucose. The weight loss market is another market that could be relevant.
If the sensor is modified, there may also be an application for animal production in
relation to animal metabolism for both meat and dairy with each of these markets
attracting billions of dollars globally. The military may also have use for this type of
sensor since food is an issue in this industry.

Reference Links
 Röder PV, Wu B, Liu, W and Han W. (2016) Pancreatic regulation of glucose

homeostasis. Exp Mol Med. 48(3): e219.
 http://www.ustfccca.org/assets/symposiums/2014/Endurance-SanMilan-
2014.pdf
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3435910/
 http://home.trainingpeaks.com/blog/article/why-athletes-need-
carbohydrates
 http://home.trainingpeaks.com/blog/article/the-importance-of-
carbohydrates-and-glycogen-for-a
 https://en.wikipedia.org/wiki/VO2_max
 http://www.runningforfitness.org/faq/vo2-max
 http://www.unm.edu/~rrobergs/478Ergometry.pdf
 https://www.sharecare.com/health/evaluating-measuring-fitness-
levels/what-watts-determine-exercise-intensity
 http://blog.eliteclubs.com/understanding-your-cardio-machine-what-are-
watts/#sthash.vhvksWC4.dpbs
 https://en.wikipedia.org/wiki/Lactate_threshold
 http://www.concept2.com/indoor-rowers/training/tips-and-general-
info/anaerobic-threshold
 http://emedicine.medscape.com/article/167027-overview
 https://en.wikipedia.org/wiki/Lactic_acidosis
 http://facstaff.bloomu.edu/jandreac/class_notes/05.575/Labs/EPOC-Lab.pdf
 http://rhinofitness.ca/articles/article_lactate_testing.html
 https://www.researchgate.net/publication/263290852_Carbohydrate_availab
ility_and_exercise_training_adaptation_Too_much_of_a_good_thing


 https://www.researchgate.net/publication/46427713_Carbohydrate_Availabil
ity_and_Training_Adaptation
 http://dailyburn.com/life/health/how-to-measure-body-fat-percentage/
 https://www.ncbi.nlm.nih.gov/pubmed/12742076
 http://www.notimpossiblenow.com/lives/future-of-measuring-stress--and-
other-things--is-in-wearable-devices
 https://www.karger.com/Article/Pdf/327398
 http://www.notimpossiblenow.com/lives/future-of-measuring-stress--and-
other-things--is-in-wearable-devices
 http://www.gssiweb.org/en/publications/all/carbohydrate
 https://breakingmuscle.com/learn/understanding-glycolysis-what-it-is-and-
how-to-feed-it
 http://www.abnewswire.com/pressreleases/smart-fitness-wear-market-is-
expected-to-grow-at-a-cagr-of-30-over-the-forecast-period-from-2016-to-
2024-market-report-by-hexa-research_86505.html
 http://www.mobihealthnews.com/41023/report-sport-fitness-wearable-
market-to-grow-29-percent-by-2019
 https://www.marketresearchfuture.com/reports/global-body-sensors-
market-research-report-forecast-to-2027
 http://www.marketresearch.com/product/sample-8982825.pdf
 https://www.maximintegrated.com/content/dam/files/design/technical-
documents/white-papers/wearable-sports-technology.pdf

Appendix A
Exercise Physiology
When an action potential from a nerve reaches the neuromuscular junction, calcium
is released from the sarcoplasmic reticulum into the cytoplasm of the muscle cell.
The calcium binds Troponin C by the actin filaments, resulting in muscle
contraction. Afterwards, the calcium is pumped back into the sarcoplasmic
reticulum by an active pump that requires energy in the form of the high energy
bonds in ATP (adenosine triphosphate). ATP is also hydrolysed by myosin during
the contraction cycling. Thus, the more the muscle contracts, the more energy in
the form of ATP is required (Figure 1).
Figure 1. Contraction of a Muscle Fiber. A cross-bridge forms between actin and the myosin heads
triggering contraction. As long as Ca++ ions remain in the sarcoplasm to bind to troponin, and as long
as ATP is available, the muscle fiber will continue to shorten.


Source: https://opentextbc.ca/anatomyandphysiology/chapter/10-3-muscle-fiber-contraction-and-
relaxation/
A limited amount of ATP can be rapidly generated by breaking down

phosphocreatine (PCr) enzymatically when adenosine diphosphate (ADP) levels
begin to accumulate in muscle.
PCr + ADP+  ATP + Cr
The creatine is converted to creatinine and excreted in the urine. The stores of PCr
are extremely limited and can only support muscle ATP levels for about 10 seconds
if there were no other sources of ATP, but given the rapidity of this source and the
localization in muscle cells, it is an important source for rapid, explosive exercise.
Anaerobic Metabolism – Glycolysis and ATP Generation
ATP is generated through several metabolic pathways, depending on many factors

however, one central mechanism relies on carbohydrate metabolism. Glycolysis is
the metabolism of glucose into pyruvate through a series of enzymatic reactions in
the cytoplasm. The free energy from this series of reactions is used to
phosphorylate ADP back into ATP and reduce nicotinamide adenine dinucleotide
(NAD+ to NADH).
The pyruvate that is generated by glycolysis can be fermented in hypoxic (i.e.

anaerobic) conditions to form lactate which can be secreted oxidizing NADH back to
NAD+ in the process, thus allowing glycolysis to proceed. This fermentation of
pyruvate to lactate is sometimes called, “anaerobic glycolysis” (i.e. anaerobic
metabolism), which only produces two ATP molecules per glucose molecule.
However, the speed at which it is can produce this energy currency is about 100
times faster than oxidative phosphorylation. It cannot be sustained for long
periods, however, since the pH in the cytoplasm quickly drops when hydrogen ions
accumulate in the muscle, eventually inhibiting the enzymes involved in glycolysis.
This drop in pH can be felt as a burning sensation in the muscles with intense
exercise.
Aerobic Metabolisms – Krebs Cycle
If oxygen is abundant, however, pyruvate can be disposed and NAD+ regenerated

by the actions of the mitochondria. The mechanisms are complex to shuttle the
NADH and pyruvate into the mitochondria, where they are then metabolized by
another series of enzymes, called the Krebs cycle (also known as the citric acid or
tricarboxylic acid (TCA) cycle). The NADH in the mitochondria is oxidized to NAD+
by the electron transport chain to create a hydrogen ion gradient across the inner
membrane of the mitochondrion, and this gradient is used to produce ATP in a


process called oxidative phosphorylation. Aerobic metabolism is much more
efficient than anaerobic metabolism, producing 30 to 32 ATP molecules from a
single glucose molecule as well as CO2 and H2O from the glucose and oxygen
consumed in the process (Figure 2). During low intensity exercise, most energy is
produced aerobically. Thus, oxygen consumption can be used as a measure of
energy use.
Figure 2: The two major metabolic pathways to product ATP in the cell: aerobic and anaerobic.
Source: http://www.differencebetween.com/difference-between-aerobic-and-vs-anaerobic-
metabolism/
Glucose Regulation
The body obtains glucose and various isometric forms through digestion, where
they are taken up by the intestines. The various forms include starch, glycogen,
disaccharides and monosaccharides. In healthy people, glucose concentration in
the blood is tightly regulated between 4-6 mM. This is regulated by a highly
sophisticated network of hormones and neuropeptides released from the brain,
pancreas, liver, intestine and adipose and muscle tissue. The central player for
blood glucose regulation is the pancreas, which produces the blood sugar lowering
hormone, insulin and its opponent glucagon. Insulin acts by promoting the
absorption of glucose from the blood into fat, liver and skeletal muscle cells. In
these cells, it is either converted into glycogen via glycogenesis or fats
(triglycerides) via lipogenesis, or in the case of liver, both. During glycogenesis,


the synthesis of glycogen, glucose molecules are added to existing glycogen to form
chains and this process takes place in liver and muscle cells when glucose and ATP
are present in high amounts. This process occurs during rest following the Cori
cycle and is activated by insulin in response to high glucose levels, for example
after ingesting a meal high in carbohydrates. Lipogenesis is the conversion of
Acetyl-CoA, produced during respiration, to fatty acids and is a way for the body to
efficiently store energy in the form of fats. Fatty acids and triglycerides are both
synthesized during lipogenesis which occurs in the cytoplasm of cells with the major
site of fatty acid synthesis being the liver and to a lesser extent adipose tissue.
Lipogenesis is stimulated by insulin and a diet high in carbohydrates as well via two
enzymatic pathways involving pyruvate dehydrogenase dephosphorylation and
acetyl carboxylase conversion.
Thus, insulin is an anabolic hormone, promoting the conversion of small molecules

in the blood into larger molecules in cells. Glucose production and release into the
blood by the liver is strongly inhibited by high concentrations of insulin. Low insulin
levels in the blood have the opposite effect by promoting catabolism. Glucagon
acts in the opposite way, by stimulating the liver to release glucose through
glycogenolysis (the breakdown of glycogen) or gluconeogenesis (the generation of
glucose from certain non-carbohydrate carbon substrates such as proteins and
lipids) (Figure 3). The levels of each of these hormones is regulated by cells in the
pancreas in response to their sensitivity to blood glucose levels. When blood
they cease to secrete, and the pancreatic alpha cells increase their glucagon
secretion into the blood.

Figure 3: Glucose production, release, and signaling
During rest, the body maintains the glucose levels and draws most of its energy
requirements from the oxidation of lipids. However, with exercise, muscle demand
for glucose can increase significantly, with uptake increasing up to 30-50X over
resting levels. The increase in muscle glucose uptake is related to the work load
and the duration of the exercise. Nevertheless, glucose homeostasis is usually
maintained despite increased glucose uptake by the working muscle, through the
catabolism of liver and muscle glycogen stores. As intensity of the exercise
increases, carbohydrate is the preferred fuel since its metabolism yields more
energy per liter of O2 than fat metabolism, and it can also produce energy in the
absence of O2 as discussed above. However, as duration increases, fat use
increases and carbohydrate use decreases since fat metabolism provides more
energy per unit mass than carbohydrate metabolism.

Figure 4: Body fuel source relation to workout intensity

Source: Powers and Howley (2007) Exercise Physiology. McGraw Hill.
Fuel selection is also driven by the need to preserve muscle glycogen. With
prolonged exercise, more energy is derived from fats and amino acids, glycerol,
lactate and pyruvate carbons are recycled into glucose to spare glycogen and thus
delay exhaustion.
The determinants of carbohydrate availability for athletes for training and

competition include exercise duration, exercise intensity, adaptation to exercise,
homeostatic needs, and fueling pre-, during, and post-activity (Bartlett et al.,
2015). Different dietary and training strategies and approaches have been
explored to optimize endurance and athletic performance. It is generally accepted


that high carbohydrate intake before exercise combined with carbohydrate
supplementation during prolonged submaximal exercise may postpone development
of muscle fatigue and enhance performance (Hawley and Burke, 2010).
Performance and fatigue will also depend on training and recovery of the athlete as
well as glycogen stores that are present in muscle and liver. To sustain muscle
energy reserves and meet the demands of training sessions, athletes typically eat
carbohydrate rich diets since fat-rich diets do not improve training capacity or
performance and impair the rate of muscle glycogenolysis and energy flux which
limits high-intensity ATP production (Hawley and Leckey, 2015).
VO2 max
The performance of athletes is often measured in terms of maximal oxygen

consumption, or VO2 max. This measurement takes into account oxygen uptake
and oxygen utilization. VO2 max (maximal oxygen consumption, maximal oxygen
uptake, peak oxygen uptake, or maximal aerobic capacity) is the maximum rate of
oxygen consumption as measured during incremental exercise. The maximal
oxygen consumption can be used to measure the aerobic physical fitness of a
person and to determine endurance capacity during prolonged sub-maximal
exercise. VO2 max can be expressed as an absolute rate in liters of oxygen per
minute or as a relative rate in milliliters of oxygen per kilogram of body mass per
minute. The rate in milliliters of O2 per kg of body mass per minute is often used to
compare the performance of endurance sports athletes. VO2 max is defined by the
Fick equation:
VO2 max = Q x (CaO2 – CvO2),
Where Q is the cardiac output of the heart, CaO2 is arterial oxygen content, and
CvO2 is venous oxygen content. These values are obtained during exertion at
maximal effort. Other estimates of VO2 max include the Uth-Sorensen-Overgaard-
Pedersen estimation, the Cooper test, the Multi-stage fitness test (or beep test),
and the Rockport fitness test. VO2 max is accepted to be the best measurement of
cardiovascular fitness and maximal aerobic power.
Work rate in watts is another tool used by exercise physiologists or trainers to

measure athletic performance or “power” of an athlete. Work, in terms of exercise
physiology, is measured using ergometry and the basic equation is the following:
W=FxD
Where W= work, F = force, and D = distance.
Watts can be used to measure the rate of energy conversion and is defined as one
joule per second. Watts, or work rate, is a measurement of the power that is being


produced by the body during activity. During exercise, power is produced by the
body and this power can be explained in calories. An athlete produces more power
the harder they are working and consequently, more calories are used or burned.
Measuring watts gives immediate and quantifiable real-time data regarding the
intensity of a workout. Watts are used to determine the caloric burn of an athlete
over time. Another equation to determine energy over a workout is the following:
Energy [kCal or calories] = Av Power [Watts] x Duration [hours] x 3.6
Using this information, an athlete can train to create power to achieve optimal
results. If the specific value of power is known, workouts can be optimized to
improve upon watts.
Anaerobic/Lactate Threshold
Another important aspect to consider during athletic training is anaerobic threshold.

Anaerobic threshold is the level of exercise intensity at which lactic acids builds in
the body faster than it can be cleared away and is also referred to at the lactate
threshold or lactate turnpoint. The lactate threshold is often explained as 85% of
maximum heart rate or 75% of maximum oxygen intake. It can also be described
as the point during exercise when the body must switch from aerobic to anaerobic
metabolism. Under normal activity, the body uses aerobic metabolism; however,
when exercise intensity is greatly increased, the body switches to anaerobic
metabolism due to the increased energy demands of the body. At this point, the
anaerobic threshold is crossed. The body burns stored sugars during anaerobic
metabolism to supply the additional energy needed, and lactic acid is produced
faster than it can be metabolized.
Measuring lactate threshold is useful in order to determine exercise intensity for

training in sports, such as racing or endurance sports. The lactate threshold varies
between athletes and can be increased with training. Lactate can be measured in
the blood but there are often variations in samples due to the status of the athlete
before exercise such as glycogen status of the athlete and ambient temperature.
Lactic acidosis, a type of metabolic acidosis, is the buildup of lactate (L-lactate) in
the body, resulting in an excessively low pH. Lactate is different from lactic acid in
that lactate is generated from the deprotonation of lactic acid and the conjugate
base of lactic acid.
Lactic acid is produced from the anaerobic breakdown of glucose in tissues. Lactate
leaves the cells, is transported to the liver and it is oxidized back to glucose. When
there is a decrease in oxygen in tissues, lactic acid is generated since anaerobic
metabolism is used to produce energy. If there is a continuation of oxygen
deprivation, the body’s buffering capacity is overwhelmed and lactic acidosis occurs.
Lactic acidosis is usually caused by a medical condition; however, it can occur


during exercise, especially excessive exercise or overtraining, when the body needs
increased energy and mitochondria cannot meet the cells’ demand for ATP.
At the onset of exercise, there is an increase in oxygen demand above resting level.
Oxygen consumption does not increase instantly, thus anaerobic metabolism is
responsible for energy production during the early phase of activity. There is a lag
in VO2 at the beginning of exercise due to the delay in delivery of oxygen to the
muscle cells’ mitochondria. The deficit in oxygen causes the body to switch to
anaerobic metabolism. Anaerobic pathways continue to provide energy until
steady-state oxygen consumption is reached which is usually a few minutes. This
delay in aerobic metabolism at the beginning of physical activity is the oxygen
deficit. Another way to describe it is the difference between total oxygen consumed
during exercise and the total that would have been consumed if steady-state
aerobic metabolism had occurred from the beginning. Due to the longer time it
takes to reach steady-state during intense exercise, this type of activity creates a
larger oxygen deficit than lower intensity activity.
Thus, measuring blood lactate concentration is a useful tool in clinical exercise

testing and blood lactate can be measured in serum /plasma or whole blood
samples. Measuring lactate is currently considered the gold standard to determine
the exercise intensity zone of an athlete to determine the effectiveness of training
for a certain physiological effect, allowing for increased accuracy in measuring how
effective a training program is. Although testing lactate is currently widely used,
measuring this parameter during exercise physiology studies has been done for
decades. Blood lactate measurements used to be carried out exclusively for top
level athletes due to the high cost of testing and the limited availability.
Additionally, this testing was previously invasive since it required taking a blood
sample. However, since the advent of portable analyzers recently, lactate
measurements can be performed for a wide range of athletes. Many different
lactate analyzers have been developed and are in use including Accusport,
Accutrend, Lactate Scout, and Lactate Plus.
Aerobic vs Anaerobic Metabolism

The metabolism of carbohydrates or energy conversion process can be anaerobic or
aerobic depending on the player’s exertion level. Other than PCr, anaerobic
metabolism is the fastest way to provide needed energy (ATP) to the working
muscles, by utilizing local muscle glycogen, however is a less efficient pathway.
Anaerobic glycolysis supplies most energy for short term intense exercise ranging
from 30 seconds to 2 minutes. It cannot be sustained for long periods, however,
since the accumulation of hydrogen ions in muscle decreases the pH and inactivates
key enzymes in the glycolytic pathway, leading to fatigue. Aerobic metabolism
supplies energy more slowly than anaerobic metabolism, but can be sustained for
much longer periods (up to five hours).


Muscle glycogen is the preferred carbohydrate fuel for events lasting less than two
hours for both aerobic and anaerobic metabolism. Depletion of muscle glycogen
causes fatigue. Both nutrition and conditioning of the athlete determine how much
work can be performed before fatigue sets in. A measure of a person’s anaerobic
threshold identifies the point at which there is no longer enough oxygen supply to
the cells to convert carbohydrates to energy aerobically. For example, during
interval training a player’s muscles need energy more quickly which can initiate
anaerobic metabolism of glucose. Aerobic metabolism fuels the body with most of
its energy need for a longer duration of time, where oxygen helps convert glucose
to ATP. In either case, high bursts of activity or longer endurance activity,
carbohydrate utilization is a key component to athletic performance.

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Notices
Please contact:
Xinova, LLC
701 Fifth Avenue, Suite 4100
Seattle, WA 98104 USA
Xinova Asia Pte. Ltd.
150 Beach Road, # 08-06/08, Gateway West
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Any distribution of this document is strictly prohibited.
This document is the proprietary and confidential information of Xinova and any
affiliate thereof.
Inquiries:
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dkraft@xinova.com
RFI template version: 4.00

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solutions.
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solutions not satisfying these requirements will not be considered.
3. Please direct any questions you may have to your local Xinova office.
Suggestions to refine, broaden or to include new information are welcome.
Any suggestions you provide are given entirely voluntarily and shall not
create any confidentiality obligation for us. We may use the suggestions
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Xinova is looking for your invention

REQUEST FOR INVENTION (RFI)

Carbohydrate Availability and

Circulation Date: Request for Invention

Xinova PROPRIETARY AND CONFIDENTIAL INFORMATION

Carbohydrate Availability and Utilization Measurement

Xinova is seeking non-invasive, portable methods to measure physiological

Sports performance is impacted by the nutrition of the athlete. Critical to

Desired invention characteristics and some suggested areas of exploration

Xinova PROPRIETARY AND CONFIDENTIAL INFORMATION 2

Carbohydrate Availability and Utilization Measurement

Xinova PROPRIETARY AND CONFIDENTIAL INFORMATION 3

Carbohydrate Availability and Utilization Measurement

Other aspects of human physiology and glucose metabolism are discussed in

Why This Problem Is Valuable to Solve

Professional and collegiate sports teams could gain a competitive advantage by

Xinova PROPRIETARY AND CONFIDENTIAL INFORMATION 4

Carbohydrate Availability and Utilization Measurement

Current Technology and Prior Solution Attempts

Muscle biopsy for glycogen concentrations

In order to get an accurate picture of carbohydrate utilization, many parameters of

Exercise physiology laboratory (O2, CO2, water, weight, controlled

Tracer studies (e.g. isotopic labels)

Xinova PROPRIETARY AND CONFIDENTIAL INFORMATION 5

Carbohydrate Availability and Utilization Measurement

Recently, technological development has focused on alternative stable isotope

Hormone monitoring (insulin/glucagon levels, others)

Current technological trends for measuring hormones in the laboratory include

Emerging technologies include a wearable sensor that is being developed to

Xinova PROPRIETARY AND CONFIDENTIAL INFORMATION 6

Carbohydrate Availability and Utilization Measurement

Metabolic control analysis (e.g. Seahorse for cellular studies)

Other Non-laboratory methods (wearables, portable measures, etc.)

Other approaches include measuring electrical signals in muscle to determine

Xinova PROPRIETARY AND CONFIDENTIAL INFORMATION 7

Carbohydrate Availability and Utilization Measurement

 Measurement of carbohydrate availability and utilization in real time during

o Continuous monitoring in-field or during performance

o Quick measurement during a break in performance (ideally <60 seconds)

 Target users are high performance athletes as well as mainstream consumers

 Data acquisition should be non-invasive and could include wearables on the

o Means for acquiring data should be portable

o Means of acquiring data for data collection can be wireless or manual

 Insulations whose properties can be controlled either at system level or

Xinova PROPRIETARY AND CONFIDENTIAL INFORMATION 8

Carbohydrate Availability and Utilization Measurement

Current Market Review

Currently, there is high demand for technologically advanced products which is

Xinova PROPRIETARY AND CONFIDENTIAL INFORMATION 9

Carbohydrate Availability and Utilization Measurement

The LEO is a more comprehensive approach that measures an array of biosignals.

Xinova PROPRIETARY AND CONFIDENTIAL INFORMATION 10

Carbohydrate Availability and Utilization Measurement

Xinova PROPRIETARY AND CONFIDENTIAL INFORMATION 11

Carbohydrate Availability and Utilization Measurement

Potential Markets and Applications

Xinova PROPRIETARY AND CONFIDENTIAL INFORMATION 12

Carbohydrate Availability and Utilization Measurement

 Röder PV, Wu B, Liu, W and Han W. (2016) Pancreatic regulation of glucose

Xinova PROPRIETARY AND CONFIDENTIAL INFORMATION 13

Carbohydrate Availability and Utilization Measurement

Xinova PROPRIETARY AND CONFIDENTIAL INFORMATION 14

Carbohydrate Availability and Utilization Measurement