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News & Views

Metabolomics: insights into


plant-based diets
Annamarie E Allen & Jason W Locasale*

Plant-based diets exclude or substantially restriction independently increases lifespan disorders (van Karnebeek & Stockler, 2012;
limit the consumption of meat and animal and causes some of the same health benefits Ahola et al, 2016; Vuong & Hsiao, 2017).
products and are of growing interest to as vegan diets such as cancer protection In this issue of EMBO Molecular Medicine,
many due to their sustainability and (Sanderson et al, 2019). Vegan diets have Hovinen† et al (2021) begin to explore these
health benefits (Eshel et al, 2016). Vegan- also been shown to change gut microbiome open questions by analyzing dietary records
ism is an extreme type of plant-based diet composition, and this may contribute to the and the serum metabolome of vegan, vegetar-
which excludes the consumption of all plasma metabolome of vegans more so than ian, and omnivore children living in Finland
animal-derived foods such as meat, eggs, omnivores (Wu et al, 2016). and particularly focus on the differences
and dairy, as well as foods containing While these and other studies have been between vegans and omnivores. They found
animal-derived ingredients. In adults, for conducted in adults, children have different that vegan children had a distinct metabolic
example, certain observational studies nutritional requirements than adults, and the profile which included differences in bile
have suggested lower body mass index, effects of vegan diets on children and associ- acid biosynthesis, circulating fatty acid levels
total cholesterol, LDL-cholesterol, decreased ated recommendations are unclear. One study including lower DHA, considerably lower
incidence and mortality from ischemic heart found vegan children tended to be smaller levels of cholesterol and high- and low-
disease, and decreased incidence of cancer than non-vegan children, but within normal density lipoproteins, alterations in circulating
in vegans and vegetarians versus omnivores ranges, and had deficits in calorie, calcium, amino acids, and lower levels of vitamins A
(Dinu et al, 2017). The mechanistic basis and vitamin D intake (Sanders, 1988). The and D that suggested possible rationale for
for these observations and their generality American Dietetic Association considers additional supplementation (Fig 1).
are unclear. vegan diets safe for all age groups including Vegan children had lower protein intake
children provided that they are well-planned, calculated as a percentage of daily energy
EMBO Mol Med (2021) 13: e13568 whereas the German Nutrition Society does intake (13.5% compared to 16.4% in omni-
See also: T Hovinen et al (February 2021) not recommend vegan diets for children. vores) and showed lower levels of circulat-
Guidelines for a vegan diet in children include ing leucine/isoleucine, phenylalanine,
consuming large amounts and a wide variety valine/betaine, and aspartate and higher

T
he direct action of metabolism, in of plant foods, choosing vegetable fats levels of alanine, arginine, and glycine.
addition to systemic effects such as selectively, consuming adequate amounts of These alterations are generally in line with
hormonal regulation and inflamma- calcium, zinc and iron, and supplementing amino acid alterations seen in adult vegans,
tion, provides a link from diet to health. vitamin D, B12, and the polyunsaturated with the notable exception of unchanged
Many aspects of whole-body metabolism fatty acid docosahexaenoic acid (DHA) serum methionine in vegan children. It
can be inferred non-invasively in humans by (Baroni et al, 2018). remains to be seen whether consuming
analyzing the metabolite composition of Besides assessing the ability of vegan differing protein sources versus a lower
plasma, which is easily accessible and offers diets to support normal growth and develop- percentage of energy consumption from
a whole-body readout of many aspects of ment, understanding the metabolic and protein contributed to the overall pattern of
physiology. Due to differences in protein physiologic effects of certain diets in chil- circulating amino acid levels in vegan chil-
composition in these diets, amino acid intake dren could offer a starting point to develop dren. It is also unclear whether the lower
and plasma levels may account for one of the new strategies for dietary management of levels of several essential amino acids could
main differences between vegan and vegetar- certain childhood disorders with limited constitute a deficiency or a health benefit, as
ian diets (Schmidt et al, 2015). Vegan diets are pharmacologic treatment options. Areas of to our knowledge there are no guidelines for
especially low in methionine which is highest interest include inborn errors of metabolism, healthy blood levels of individual amino
in red meat, eggs, and dairy, and methionine mitochondrial disease, and autism spectrum acids and their effects on metabolism are

Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA
*Corresponding author. E-mail: dr.jason.locasale@gmail.com

Correction added on 11 February 2021, after first online publication: The author's surname has been corrected in all instances from Hovenin to Hovinen.
DOI 10.15252/emmm.202013568 | EMBO Mol Med (2021) 13: e13568

ª 2021 The Authors. Published under the terms of the CC BY 4.0 license EMBO Molecular Medicine 13: e13568 | 2021 1 of 2
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EMBO Molecular Medicine Annamarie E Allen & Jason W Locasale

VEGAN DIET
Modified Atkins diet induces subacute selective
ragged-red-fiber lysis in mitochondrial
myopathy patients. EMBO Mol Med 8:
ADULTS 1234 – 1247
Baroni L, Goggi S, Battaglino R, Berveglieri M,
Data linked to better
health outcomes Fasan I, Filippin D, Griffith P, Rizzo G, Tomasini
• Heart disease C, Tosatti MA et al (2018) Vegan nutrition for
• Cancer mothers and children: practical tools for
• BMI healthcare providers. Nutrients 11: 5
• Cholesterol
Dinu M, Abbate R, Gensini GF, Casini A, Sofi F
(2017) Vegetarian, vegan diets and multiple
Biological changes health outcomes: a systematic review with
CHILDREN
• Distinct plasma meta-analysis of observational studies. Crit Rev
metabolome Limited data on
• Altered gut microbiome Food Sci Nutr 57: 3640 – 3649
health and development
Eshel G, Shepon A, Noor E, Milo R (2016)
Biological changes Environmentally optimal, nutritionally aware
(Hovinen et al, 2021)
beef replacement plant-based diets. Environ Sci
• Distinct plasma metabolome
• Possible nutrient deficiencies Technol 50: 8164 – 8168
in • Vitamin A Hovinen T, Korkalo L, Freese R, Skaffari E,
• Vitamin D Isohanni P, Niemi M, Nevalainen J, Gylling H,
• Cholesterol
• DHA Zamboni N, Erkkola M et al (2021) Vegan diet
in young children remodels metabolism and
challenges the statuses of essential nutrients.
EMBO Mol Med 13: e13492

© EMBO
van Karnebeek CD, Stockler S (2012) Treatable
inborn errors of metabolism causing
intellectual disability: a systematic literature
Figure 1. Vegan diets are defined by their exclusion of animal-derived foods including meat, eggs,
and dairy. review. Mol Genet Metab 105: 368 – 381
In adults, vegan diets have been linked to improved health outcomes and adults consuming a vegan diet Sanders TA (1988) Growth and development of
show biological changes including distinct alterations in their plasma metabolome and gut microbiome. Less British vegan children. Am J Clin Nutr 48:
is known about how vegan diets affect children, and to this end, Hovinen et al (2021) explore the metabolic 822 – 825
and nutritional effects of vegan diets in children.
Sanderson SM, Gao X, Dai Z, Locasale JW (2019)
Methionine metabolism in health and cancer: a
nexus of diet and precision medicine. Nat Rev
still in its early stages. Perhaps relevant is In conclusion, Hovinen et al (2021) use Cancer 19: 625 – 637
the low levels of total cholesterol and high- metabolomics to study the metabolic and Schmidt JA, Rinaldi S, Ferrari P, Carayol M, Achaintre
and low-density lipoproteins seen in vegan nutritional consequences of vegan diets in D, Scalbert A, Cross AJ, Gunter MJ, Fensom GK,
children along with the indicators that there children and find similarities and differences Appleby PN et al (2015) Metabolic profiles of
is not compensatory cholesterol biosynthe- to what has been previously observed in male meat eaters, fish eaters, vegetarians, and
sis. Blood cholesterol also does not have adults. This leads to many open questions as vegans from the EPIC-Oxford cohort. Am J Clin
clearly defined deficiency levels, and as to how these types of diets might be used to Nutr 102: 1518 – 1526
Hovinen et al (2021) note, cholesterol is affect specific aspects of metabolism and Vuong HE, Hsiao EY (2017) Emerging roles for the
required for cell membrane synthesis and downstream health consequences such as gut microbiome in autism spectrum disorder.
steroid hormone synthesis among its other development. Given the metabolic hetero- Biol Psychiatry 81: 411 – 423
roles and may be required at higher levels geneity observed across the population, it’s Wu GD, Compher C, Chen EZ, Smith SA, Shah RD,
during development. unlikely that a vegan diet would be benefi- Bittinger K, Chehoud C, Albenberg LG, Nessel L,
Pathway analysis on the untargeted meta- cial all in all settings. Nevertheless, certain Gilroy E et al (2016) Comparative metabolomics
bolomics data showed bile acid biosynthesis children exhibited specific metabolic profiles in vegans and omnivores reveal constraints on
was the largest pathway alteration in vegan that suggest that they could be specifically diet-dependent gut microbiota metabolite
children. Pathway alterations included affected by the vegan diet. More work is production. Gut 65: 63 – 72
higher levels of unconjugated primary bile needed to know whether such observations
acids and a lower taurine to glycine conjuga- have molecular consequences and their
tion ratio of bile acids in vegans than in generalizability.
omnivores, and however, authors note that License: This is an open access article under the
it is unknown how these changes are likely References terms of the Creative Commons Attribution License,
to affect the roles of bile acids in digestion, Ahola S, Auranen M, Isohanni P, Niemisalo S, Urho which permits use, distribution and reproduction
absorption, endocrine, and gut microbiome– N, Buzkova J, Velagapudi V, Lundbom N, in any medium, provided the original work is prop-
brain interactions. Hakkarainen A, Muurinen T et al (2016) erly cited.

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