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The postprandial metabolome — a source of Nutritional
Biomarkers of Health
Grégory Pimentel1,2, Kathryn J Burton2, François P Pralong2,
Nathalie Vionnet2, Reto Portmann1 and Guy Vergères1
The novel concept of ‘Nutritional Biomarkers of Health’ (NBH) is
introduced in this paper. In analogy to glucose, metabolites in
blood that (i) respond postprandially to the ingestion of foods,
(ii) differentiate healthy individuals from individuals with
metabolic diseases under fasting and/or postprandial
conditions, and (iii) have plausible mechanisms that associate
them with metabolic diseases, may qualify as NBHs. The use of
metabolomics to link food composition to the metabolic status
of a subject after ingestion offers a unique approach for the
identification of NBHs and thus, the discovery and
development of dietary solutions that prevent disease and
promote health.
Addresses
1
Agroscope, Federal Office of Agriculture, Bern, Switzerland
2
University Hospital CHUV, Service of Endocrinology, Diabetes and
Metabolism, Lausanne, Switzerland
Corresponding author: Vergères, Guy
(guy.vergeres@agroscope.admin.ch)
Current Opinion in Food Science 2017, 16:67–73
This review comes from a themed issue on Foodomics technologies
Edited by Francesco Capozzi, Alessandra Bordoni and Alejandro
Cifuentes
For a complete overview see the Issue
Available online 1st September 2017
http://dx.doi.org/10.1016/j.cofs.2017.08.006
2214-7993/ã 2017 The Authors. Published by Elsevier Ltd. This is an
open access article under the CC BY-NC-ND license (http://creative-
commons.org/licenses/by-nc-nd/4.0/).
Introduction
The original WHO definition of health ‘Health is a state of
complete physical, mental and social well-being and not merely
the absence of disease or infirmity’ published in 1948 [1] is in
line with the perceived mission of nutritional sciences,
which focus on maintaining health rather than on the
curing of disease. However, this description defines
health from a static point of view, which is no longer
in line with the current knowledge, and consequently a
more dynamic definition of health was proposed in
2011 ‘Health is the ability to adapt and to self-manage, in
the face of social, physical and emotional challenges’ [2,3]. A
dynamic definition of health can translate into a
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nutritional research strategy that includes the notion of
‘nutritional phenotypic flexibility’, which can experimen-
tally be studied by measuring the postprandial response
of the human organism to dietary challenges [4,5]. This
position paper builds on this strategy by proposing the
new concept of NBHs and by illustrating how metabo-
lomics can support this research field.
The concept of Nutritional Biomarkers of
Health
In line with the dynamic model of health, postprandial
glucose is considered a stronger risk factor for cardiovas-
cular diseases than fasting glucose [6] and foods that
induce lower postprandial glycemic responses (low-GI
foods) form a key element of nutritional policies that seek
to prevent metabolic diseases [7]. Glucose is therefore a
metabolite that links food properties to the state of health
and that can be used to appropriately select and design
personalized diets [8], that prevent or limit the develop-
ment of metabolic diseases, in particular cardiovascular
diseases [9] and diabetes [10].
In analogy to the use of glucose as a biomarker of
metabolic health, we propose that other metabolites in
blood or urine could also be exploited as nutrition-related
biomarkers that respond to health status; Nutritional
Biomarkers of Health (NBHs) thus integrate food and
nutritional/medical sciences. Similarly to glucose, these
metabolites would need to respond to the ingestion of
foods as well as to differentiate healthy individuals from
individuals with a metabolic dysfunction under fasting
and/or postprandial conditions. In addition, plausible
mechanisms should associate them with metabolic dis-
eases in order for them to qualify as NBHs. The selection
of the wording ‘Health’, instead of ‘Health and Disease’
in the acronym NBHs, purposely highlights the intrinsic
preventive nature of nutrition, this despite the difficulty
in defining health without reference to disease states.
Few metabolites that can be defined as NBHs (e.g.,
glucose, triglycerides) have been validated. There is, how-
ever, no reason why NBHs should be restricted to these
molecules given that the Human Metabolome Database
reports more than 40 000 molecules identified in human
tissues [11] and that the food metabolome, that is, the part
of the human metabolome directly derived from the
digestion and biotransformation of foods and their consti-
tuents, comprises >25 000 compounds [12]. That the
Current Opinion in Food Science 2017, 16:67–73
68 Foodomics technologies
human metabolome contains such a high proportion of
molecules originating from food is both surprising and
logical. It is surprising in the context of the large contribu-
tion of medical sciences to our knowledge on human
biology, a science that highlights endogenously produced
molecules. It is, however, logical given the basic biochem-
ical role of nutrition as the major source of building blocks
that ultimately constitute our organism [13].
Metabolomics in the characterization of
human metabolic health and disease
The development of metabolomic profiling methods has
led to the availability of resources that open new avenues
in the study of human biology [11]. Indeed, profiling of a
multitude of metabolites is evolving as a key technology
to define health in human populations. Recently, Dunn
et al. [14] analyzed the serum metabolome of
1200 healthy adults from the UK and characterized
inter-individual variability by gender, age, BMI, blood
pressure, and smoking habits of these subjects. The
serum metabolome can also be used to identify markers
that are associated with disease, in particular metabolic
such as obesity, diabetes and cardiovascular diseases
[15]. By combining the characterization of these two
populations, metabolomic profiling will increasingly pro-
vide detailed insights into the metabolic trajectories
leading from a healthy organism to a state of disease
and, consequently, allow the introduction of preventive
measures in populations at risk.
Although environmental factors are crucial for determin-
ing these metabolic trajectories, metabolic profiling has
not yet systematically integrated the analysis of environ-
mental impacts, in particular the diet, on human metabo-
lism. Although the important contribution of the food
metabolome to the human metabolome is recognized
[12], there is a lack of understanding of the dynamics
and functional properties of the food metabolome. In
comparison to the clinical relevance of the glycemic
response we propose that other NBHs can also link food
intake to human metabolism and health. To fully exploit
the NBHs concept it is important to respond to the
following questions pertaining to the field of metabolo-
mics: Which parts of the human metabolome change
postprandially? How does food composition affect the
postprandial metabolome? What are the potential func-
tional properties of the food metabolome? How is the
postprandial food metabolome related to metabolic dis-
eases? Answering these questions will help to use NBHs
to link the properties of foods to human health.
The remaining part of this paper will consider these
questions using data from a recently published human
intervention study [16] and thus illustrate the concept of
NBHs. The data relates to a randomized crossover study
that was conducted to evaluate the metabolic and inflam-
matory responses of healthy men after a two-week dietary
Current Opinion in Food Science 2017, 16:67–73
intervention comprising either a probiotic yoghurt or an
acidified milk [16]. Of interest to this report, this study
also allowed the characterization of the postprandial
serum metabolome of these subjects after an acute inges-
tion of the two dairy products tested as well as of a high-
fat meal. The design of the study has been published
elsewhere [16].
Metabolomics for the characterization of the
postprandial metabolome
The first question that can be addressed by postprandial
metabolomics is the fraction of the serum metabolome
that is influenced by the ingestion of food. Figure 1
suggests that, in the context of the many variables that
differentiate the three meals analyzed [16] (food group,
bacterial content, texture, caloric content, macronutrient
composition), this fraction varies from one third to half of
the serum metabolome (36% for acidified milk, 43% for
the probiotic yoghurt, 48% for the high-fat meal), which is
a surprisingly high proportion of the metabolome to be
affected. Among the 759 metabolites that show a
Figure 1
Yogurt intake
640 Serum metabolome
1785
121
64
48 407
247
169
135
High-fat meal
Milk intake 853
759
Current Opinion in Food Science
Quantitative evaluation of the postprandial response of the human
serum metabolome in response to the intake of three different meals.
The postprandial serum metabolome of 14 subjects having ingested
three different meals in a crossover design was measured over a time
period of 0–6 h by untargeted metabolomics using LC–MS.
Metabolites with a significant postprandial response (significant time
effect, R3.1.2, nparLD package) are shown and compared to the total
number of metabolites identified in a QC sample composed of a mix
of fasting and postprandial sera using the same procedure
(1785 metabolites). The high-fat meal was composed of bread, salami,
eggs and palm oil and contained 3.9 MJ, 57 g carbohydrate (25%
energy), 47 g proteins (20% energy), 54 g fat (53% energy). The yogurt
meal contained 2.1 MJ, 22 g carbohydrate (17% energy), 27 g proteins
(22% energy), 28 g fat (50% energy). Milk was acidified with glucono-
delta lactone for texture purpose, and contained 2.4 MJ, 39 g
carbohydrate (26% energy), 26 g proteins (18% energy), 27 g fat (42%
energy). The design of the intervention study has been published
elsewhere [16].
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postprandial response after acidified milk intake, 60% are
also modulated after probiotic yogurt intake compared to
71% that are also modulated after the high-fat meal
intake. Even though the core postprandial metabolome
is expected to decrease as the number of tested meals is
increased, Figure 1 still reveals significant similarity
between the responses to the three meals; 23% of the
serum metabolome is changed postprandially by all three
meals.
Strikingly, compared to the 1785 metabolites measured in
the reference serum composed of a mix of fasting and
postprandial sera, the fasting metabolome identified in
this study contained 1763 metabolites and, thus, only few
additional molecules were identified in the postprandial
serum after ingestion of the three meals. This observation
illustrates one of the criteria that is fundamental to the
concept of NBH that is the detection of these markers in
both fasting and postprandial states. The striking similar-
ities observed conceptualizes one of the main lessons
learned from classical nutritional biochemistry, which is
that the human organism is remarkably efficient in decon-
structing a wide range of molecules in foods to absorb
basic nutrients such as amino acids, fatty acids, and simple
sugars, which are finally reconstructed to form the mole-
cules that constitute the human body. Thus, the post-
prandial state shows a dynamic modulation of metabolites
that are also present in the fasting state. These observa-
tions are also illustrative of the immunological vision of
nutrition that describes the combined ability of the diges-
tive and immune systems to turn the foreign dietary
environment, composed of a large number of molecules,
into, either metabolites that are processed to be recog-
nized as self and integrated into the organism [17], or
xenobiotics that are detoxified and/or excreted. Of note,
the postprandial metabolome may reflect the activation of
endogenous metabolic pathways sensitive to food intake
or absorbed macronutrients present in the meals
[12,18], but may also be influenced by metabolites
reflecting circadian processes [19].
The next obvious question that can be addressed while
characterizing the postprandial metabolome is the extent
to which it can be modified by changing the properties of
the ingested meals. Despite the identified homologies,
Figure 1 also reflects postprandial differences in the
response of the organism to different meals. In this regard,
9% of the metabolome showed a postprandial response
only after the ingestion of milk, 7% only after the inges-
tion of yogurt, and 14% only after the high-fat meal. The
postprandial metabolome can thus be used to characterize
the specific impact of particular foods and meals on the
organism. On the other hand, these numbers also illus-
trate one of the main challenges in nutritional research,
which is the selection of control, reference foods to which
dietary effects can be compared. Indeed the number of
metabolites that respond postprandially only after the
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Nutritional Biomarkers of Health Pimentel et al. 69
ingestion of one particular food is expected to decrease
as the number of ‘control’ foods is increased. As such, in
nutritional science, the properties of the test food or diet
should not be compared to a single food, but should rather
be defined by their specificity compared to all other foods
in the diet! In opposition to the immunological vision of
nutrition stated above, the ability of metabolomics to
detect food-specific metabolites in serum highlights the
other side of the ‘postprandial metabolomic coin’, which
is the concept presented by Anthelme Brillat-Savarin in
1826 ‘Tell me what you eat and I will tell you what you are’.
The capacity of the organism to dynamically respond to a
dietary challenge can further be evaluated by measuring
the resilience of the serum metabolome when exposed to
a variety of foods, that is, its ability to return to baseline
values after postprandial activation. To illustrate this, the
left panel of Figure 2 presents the clustering of the
853 metabolites that have a significant postprandial
response after milk intake. Notably, there are as many
metabolites that increase postprandially (clusters 3, 5 and
6, 53%) as metabolites that decrease postprandially (clus-
ters 1, 2 and 4, 47%). In addition, the time window
necessary to capture the kinetic patterns of the metabo-
lites differs, a 6 h window being appropriate to capture
the majority of changes, including their return to the
baseline. However, another category of metabolites con-
tinue to increase (cluster 5) or decrease (cluster 6) at 6 h.
Independently of their origin (i.e., exogenously derived
from the meal or endogenously derived from the organ-
ism), both kinetic clusters are interesting in their own
right. The rapid increase or decrease (clusters 1, 2, 3 and
6) might be considered in the context of an expected
response of a healthy organism to a meal challenge; the
‘metabolic flexibility’ of the organism allows this flux
before the return of these molecules to their fasting levels
in preparation for another meal. Deviation from these
kinetics (clusters 4 and 6) could be an indicator of a longer
digestive process, due to nutrients that are poorly
digested and absorbed or from a metabolic dysfunction
[20]. In addition, due to their longer clearance time,
metabolites in this cluster could potentially accumulate
over time if the same meal is repeatedly taken, thus
providing interesting targets of molecules that could be
indicators of the health or nutritional status of the
consumers.
Of note, a dynamic analysis of the response of the
organism to the ingestion of food can also identify
variations in the metabolism of the consumers. Krug
et al. [21] noted that the inter-individual variability of
metabolites involved in anabolism is highest during the
hours following a dietary challenge. Comparing individ-
uals during the postprandial phase that reflects their
ability to assimilate very different meals might thus
represent an effective approach to identify different
Current Opinion in Food Science 2017, 16:67–73
70 Foodomics technologies

Figure 2

8 6 4 2 0 Milk intake Yogurt intake High-fat Meal

0min 120min 360min 0min 120min 360min 0min 120min 360min
1
6%

2
23%

3
22%

4
18%

5
8%

6
23%

Current Opinion in Food Science

Evaluation of the postprandial dynamic response of the human serum metabolome in response to the intake of different meals. Kinetic clustering
of the 759 metabolites that show a significant postprandial response after milk intake and their respective behavior after yogurt and high-fat meal
intake (Spearman’s distance measure and complete linkage for clustering, R 3.1.2, amap and dendextend packages). The design of the
intervention study has been published elsewhere [16].

metabotypes and, thus, promote the development of
personalized nutrition.
Closing the gap with functional analyses of
the metabolome
With the increasing sensitivity of mass spectrometry
together with the powerful analytical capacity of multi-
variate statistical tools, metabolomics is now able to
detect and discriminate hundreds of metabolites that
show postprandial variation in blood and urine. However,
once the identities of such metabolites are confirmed
(identification remaining a major bottleneck in metabo-
lomics [22]), their link with health status has to be
established in order to qualify as NBHs. The use of
metabolomics data from interventional and observational
studies that compare the metabolic status of healthy
subjects to that of subjects with specific metabolic dis-
orders may help addressing this question.
The above strategy can, again be illustrated by the
specific example from the study already presented in
Figures 1 and 2 [16]. Figure 3 shows the postprandial
behavior of the essential amino acid, phenylalanine, after
ingestion of each of the three meals at 2 h and 6 h. In light
of the same amount of protein ingested by the volunteers
after each of the two dairy meals, Figure 3 illustrates the
impact of fermentation of the milk matrix on the bio-
availability of phenylalanine, serum levels being signifi-
cantly higher after yogurt intake compared to acidified
milk intake. Notably, postprandial phenylalanine was
almost as elevated 2 h after the ingestion of the probiotic
yoghurt compared with the high-fat meal, which contains
almost twice as much protein.
In the context of the concept of NBHs, the postprandial
behavior of phenylalanine, among others essential amino
acids, should be related to its decreased levels under
pathological conditions, in particular in the blood of
elderly patients with malnutrition [23] as well as in
muscular tissues of patients with neuromuscular diseases
[24]. Indeed the imbalance between synthesis and deg-
radation of muscle proteins in these populations is
strongly dependent on the efficient delivery and meta-
bolic use of essential amino acids, including phenylala-
nine [25,26,27]. Also, supplementation of this population
with essential amino acids is a valid clinical approach [28–

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Figure 3
Phenylalanine
1.0 Milk intake
Yoghurt intake
High fat meal
0.5
Intensity (A.U.)
0.0
−0.5
0 120
Postprandial response of phenylalanine in the serum of subjects having ingested the acidified milk, probiotic yoghurt or the high-fat meal.
*
Adjusted P value < 0.05, paired Wilcoxon signed-rank test, Benjamini–Hochberg’s correction. The design of the intervention study has been
published elsewhere [16].
30]. Finally, milk proteins, in particular whey protein,
play a particular role in the clinical management of
sarcopenia in aging [31–35]. Figure 3 therefore suggests
that the potential of milk to support the delivery of
essential amino acids to the organism in order to support
muscle health can be further enhanced by technological
fermentation. It also highlights the potential of the meta-
bolomic analytical strategy in identifying NBHs.
Making use of validated clinical biomarkers
toward the establishment of causality for
NBHs
An additional tool in the search for NBHs is the ability to
statistically correlate, and mechanistically associate, the
information obtained from metabolic profiling with, and
to, validated postprandial markers. In light of the existing
challenges associated with the identification of validated
clinically-relevant biomarkers [36], this task is certainly
the most critical part of the NBH concept. For illustration,
postprandial insulin, but not glucose, was statistically
significantly increased after intake of the probiotic yoghurt
compared to the acidified milk (KJ. Burton et al, unpub-
lished). Insulin is a key molecule in muscle biology and
the management of related pathologies, for example, in
elderly, as it promotes muscle anabolism [25,37,38].
Whey proteins possess insulinotropic properties and these
properties are increased upon hydrolysis of whey, in
particular via the insulin secretagogue activity of branched
chain amino acids and phenylalanine [39]. That the
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Nutritional Biomarkers of Health Pimentel et al. 71
*
*
360
Time (min)
Current Opinion in Food Science
fermentation of milk to probiotic yoghurt not only
increases the bioavailability of essential amino acids,
among these phenylalanine, but also increases postpran-
dial insulin suggests a potential contribution of these
products to the management of muscle health.
Conclusions
The identification of metabolites that both show specific
postprandial appearance in the organism depending on
the qualities of the ingested foods and that are causally
associated with metabolic disorders, provides an exciting
approach to exploit the preventive health qualities of diet.
The identification of such markers, defined here as
NBHs, can be facilitated by the current development
in metabolomic technologies that will strengthen collab-
oration between food and nutrition scientists.
Conflict of interest
All authors declare no actual or potential conflicts of
interest.
Acknowledgement
This work was funded by Agroscope.
References and recommended reading
Papers of particular interest, published within the period of review,
have been highlighted as:
 of special interest
 of outstanding interest
Current Opinion in Food Science 2017, 16:67–73
72 Foodomics technologies
1. World Health Organization: Preamble to the Constitution of the
World Health Organization as adopted by the International Health
Conference; New York, 19–22 June, 1946; signed on 22 July
1946 by the representatives of 61 States and entered into force on
7 April 1948: Official Records of the World Health Organization
1946, 2:100.
2. Huber M, van Vliet M, Giezenberg M, Winkens B, Heerkens Y,
Dagnelie PC, Knottnerus JA: Towards a ‘patient-centred’
operationalisation of the new dynamic concept of health: a
mixed methods study. BMJ Open 2016, 6:e010091.
3. Huber M, Knottnerus JA, Green L, van der Horst H, Jadad AR,
Kromhout D, Leonard B, Lorig K, Loureiro MI, van der Meer JW
et al.: How should we define health? BMJ 2011, 343:d4163.
4. Kardinaal AF, van Erk MJ, Dutman AE, Stroeve JH, van de Steeg E,
 Bijlsma S, Kooistra T, van Ommen B, Wopereis S: Quantifying
phenotypic flexibility as the response to a high-fat challenge
test in different states of metabolic health. FASEB J 2015,
29:4600-4613.
This study quantifies the metabolic adaptation capacity of healthy men
and patients with the metabolic syndrome by studying challenge
response curves and demonstrates that change in challenge response
is a sensitive biomarker of metabolic health.
5. Lee S, Norheim F, Langleite TM, Noreng HJ, Storas TH, Afman LA,
Frost G, Bell JD, Thomas EL, Kolnes KJ et al.: Effect of energy
restriction and physical exercise intervention on phenotypic
flexibility as examined by transcriptomics analyses of mRNA
from adipose tissue and whole body magnetic resonance
imaging. Physiol Rep 2016:4.
6. Middelbeek RJ, Horton ES: The role of glucose as an
independent cardiovascular risk factor. Curr Diab Rep 2007,
7:43-49.
7. Bjorck I, Liljeberg H, Ostman E: Low glycaemic-index foods. Br J
Nutr 2000, 83(Suppl. 1):S149-S155.
8. Zeevi D, Korem T, Zmora N, Israeli D, Rothschild D, Weinberger A,
Ben-Yacov O, Lador D, Avnit-Sagi T, Lotan-Pompan M et al.:
Personalized nutrition by prediction of glycemic responses.
Cell 2015, 163:1079-1094.
9. Gerstein HC: Glucose: a continuous risk factor for
cardiovascular disease. Diabet Med 1997, 14(Suppl. 3):S25-
S31.
10. Hong S, Kang JG, Kim CS, Lee SJ, Lee CB, Ihm SH: Comparison
of the clinical characteristics of diabetes mellitus diagnosed
using fasting plasma glucose and haemoglobin A1c: the
2011 Korea National Health and Nutrition Examination Survey.
Diabetes Res Clin Pract 2016, 113:23-25.
11. Wishart DS, Jewison T, Guo AC, Wilson M, Knox C, Liu Y,
Djoumbou Y, Mandal R, Aziat F, Dong E et al.: HMDB 3.0 — the
human metabolome database in 2013. Nucleic Acids Res 2013,
41:D801-D807.
12. Scalbert A, Brennan L, Manach C, Andres-Lacueva C,
 Dragsted LO, Draper J, Rappaport SM, van der Hooft JJ,
Wishart DS: The food metabolome: a window over dietary
exposure. Am J Clin Nutr 2014, 99:1286-1308.
This review presents the properties of the food metabolome and makes
recommendations for the development of databases, software tools, and
chemical libraries to discover bioactive molecules and dietary factors
associated with diseases.
13. Mongardon N, Singer M: The evolutionary role of nutrition and
metabolic support in critical illness. Crit Care Clin 2010, 26:443-
450 vii–viii.
14. Dunn WB, Lin W, Broadhurst D, Begley P, Brown M, Zelena E,
 Vaughan AA, Halsall A, Harding N, Knowles JD et al.: Molecular
phenotyping of a UK population: defining the human serum
metabolome. Metabolomics 2015, 11:9-26.
This study has phenotyped the variability of the serum metabolome of
1200 healthy adults, providing a reference dataset for understanding the
‘normal’ relative concentrations and variation in the human serum
metabolome.
15. Newgard CB: Metabolomics and metabolic diseases: where do
 we stand? Cell Metab 2017, 25:43-56.
Current Opinion in Food Science 2017, 16:67–73
This review presents recent advances in metabolomic technologies and
their application to defining predictive biomarkers for incident cardiome-
tabolic diseases.
16. Burton K, Rosikiewicz M, Pimentel G, Bütikofer U, von Ah U,
Voirol M-J, Croxatto A, Aeby S, Drai J, McTernan P et al.: Probiotic
yoghurt and acidified milk similarly reduce postprandial
inflammation and both alter the gut microbiota of healthy,
young men. Br J Nutr 2017, 117:1312-1322.
17. Stanley S: Oral tolerance of food. Curr Allergy Asthma Rep 2002,
2:73-77.
18. Polakof S, Rémond D, Rambeau M, Pujos-Guillot E, Sébédio J-L,
 Dardevet D, Comte B, Savary-Auzeloux I: Postprandial
metabolic events in mini-pigs: new insights from a combined
approach using plasma metabolomics, tissue gene
expression, and enzyme activity. Metabolomics 2015, 11:964-
979.
This study describes, in mini-pigs, the plasma metabolome in fasting and
postprandial states. Interestingly, the postprandial metabolome is clas-
sified into four main kinetic profiles. The article also discusses the
potential of postprandial metabolomics in nutrition research.
19. Dallmann R, Viola AU, Tarokh L, Cajochen C, Brown SA: The
human circadian metabolome. Proc Natl Acad Sci U S A 2012,
109:2625-2629.
20. Margioris AN: Fatty acids and postprandial inflammation. Curr
Opin Clin Nutr Metab Care 2009, 12:129-137.
21. Krug S, Kastenmuller G, Stuckler F, Rist MJ, Skurk T, Sailer M,
Raffler J, Romisch-Margl W, Adamski J, Prehn C et al.: The
dynamic range of the human metabolome revealed by
challenges. FASEB J 2012, 26:2607-2619.
22. Wang L, Ye H, Sun D, Meng T, Cao L, Wu M, Zhao M, Wang Y,
Chen B, Xu X et al.: Metabolic pathway extension approach for
metabolomic biomarker identification. Anal Chem 2017,
89:1229-1237.
23. Polge A, Bancel E, Bellet H, Strubel D, Poirey S, Peray P, Carlet C,
Magnan de Bornier B: Plasma amino acid concentrations in
elderly patients with protein energy malnutrition. Age Ageing
1997, 26:457-462.
24. Stuerenburg HJ, Stangneth B, Schoser BG: Age related profiles
of free amino acids in human skeletal muscle. Neuro Endocrinol
Lett 2006, 27:133-136.
25. Gorissen SH, Remond D, van Loon LJ: The muscle protein
 synthetic response to food ingestion. Meat Sci 2015, 109:96-
100.
This review discusses the mechanistic links between dairy and meat
protein composition, the postprandial response in essential amino acids
resulting from the ingestion of these products, and the potential of these
foods to prevent loss in skeletal muscle during aging.
26. Timmerman KL, Volpi E: Amino acid metabolism and regulatory
effects in aging. Curr Opin Clin Nutr Metab Care 2008, 11:45-49.
27. Volpi E, Kobayashi H, Sheffield-Moore M, Mittendorfer B,
Wolfe RR: Essential amino acids are primarily responsible for
the amino acid stimulation of muscle protein anabolism in
healthy elderly adults. Am J Clin Nutr 2003, 78:250-258.
28. Rasmussen BB, Wolfe RR, Volpi E: Oral and intravenously
administered amino acids produce similar effects on muscle
protein synthesis in the elderly. J Nutr Health Aging 2002, 6:358-
362.
29. Henderson GC, Irving BA, Nair KS: Potential application of
essential amino acid supplementation to treat sarcopenia in
elderly people. J Clin Endocrinol Metab 2009, 94:1524-1526.
30. van Vliet S, Burd NA, van Loon LJ: The skeletal muscle anabolic
response to plant-versus animal-based protein consumption.
J Nutr 2015, 145:1981-1991.
31. Beasley JM, Shikany JM, Thomson CA: The role of dietary
protein intake in the prevention of sarcopenia of aging. Nutr
Clin Pract 2013, 28:684-690.
32. Yanai H: Nutrition for sarcopenia. J Clin Med Res 2015, 7:926-
931.
www.sciencedirect.com

33. Devries MC, Phillips SM: Supplemental protein in support of
muscle mass and health: advantage whey. J Food Sci 2015, 80
(Suppl. 1) A8–a15.
34. Wolfe RR: Update on protein intake: importance of milk
proteins for health status of the elderly. Nutr Rev 2015, 73
(Suppl. 1):41-47.
35. Pennings B, Boirie Y, Senden JM, Gijsen AP, Kuipers H, van
Loon LJ: Whey protein stimulates postprandial muscle protein
accretion more effectively than do casein and casein
hydrolysate in older men. Am J Clin Nutr 2011, 93:997-1005.
36. Kempsell KE, Ball G, Szakmany T: Issues in biomarker
identification, validation and development for disease
www.sciencedirect.com
Nutritional Biomarkers of Health Pimentel et al. 73
diagnostics in public health. Expert Rev Mol Diagn 2016, 16:383-
386.
37. Fujita S, Rasmussen BB, Cadenas JG, Grady JJ, Volpi E: Effect of
insulin on human skeletal muscle protein synthesis is
modulated by insulin-induced changes in muscle blood flow
and amino acid availability. Am J Physiol Endocrinol Metab 2006,
291:E745-E754.
38. Rasmussen BB, Fujita S, Wolfe RR, Mittendorfer B, Roy M,
Rowe VL, Volpi E: Insulin resistance of muscle protein
metabolism in aging. FASEB J 2006, 20:768-769.
39. Power O, Hallihan A, Jakeman P: Human insulinotropic
response to oral ingestion of native and hydrolysed whey
protein. Amino Acids 2009, 37:333-339.
Current Opinion in Food Science 2017, 16:67–73