Not all (micro)nutrients are easily obtained from plants

Animal source foods are rich in high-quality protein, long-chain n-3 fatty acids, minerals (calcium, iron, zinc, iodine, etc), vitamins (A, B12, D, K2, etc), and other bioactive compounds (taurine, creatine, etc.) These nutrients pose practical and nutritional challenges when eating plants only. Diets that limit the consumption of animal source food to very low levels require careful fortification or supplementation, and the inclusion of specific nutrient-dense plants. If these cautionary measures are neglected, vegetarian and, especially, vegan populations risk to suffer from deficiencies in some key animal source food-associated nutrients.

The following nutritional benefits of animal source foods will be discussed (for protein, see elsewhere):

• Complementarity within the omnivore spectrum
• Long-chain omega-3 fatty acids (EPA/DHA)
• Vitamin A (retinol)
• Vitamin B12 (cobalamin)
• B vitamins (other than B12)
• Vitamin K2 (menaquinones)
• Calcium and vitamin D
• (Haem) iron
• Zinc
• Iodine
• Selenium
• Choline
• Other bioactive compounds

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Benefits and complementarity within the omnivore spectrum

Optimal nutrient intake and health are more likely when foods derived from both plants and animals are appropriately combined. Composing nutritionally adequate whole food-based diets is facilitated when at least one-third of the caloric intake or half of the protein is sourced from animals. Below that level, as in the EAT-Lancet diet, deficiencies in some of the priority vitamins and minerals become difficult to avoid. Vegan and vegetarian populations in various countries have been found to have micronutrient deficiencies, potentially leading to health risks like bone fractures, sarcopenia, anaemia, and depression. 

Further reading (summary of the scientific literature): 

Animal source foods (ASFs) are excellent sources of nutrients needed for good health [Murphy & Allen 2003; Leroy & Barnard 2020]. This has been argued for meat [Lombardi-Boccia et al. 2004; Williams 2007; McAfee et al. 2010; Pereira & Vicente 2013; Young et al. 2013; McNeill 2014; Pighin et al. 2016; Leroy & Cofnas 2020; Fulgoni & Fulgoni 2023; Kehoe et al. 2023; Ruxton & Gordon 2024], fish and seafood [Kawarazuka 2010; Oehlenschläger 2012], dairy [Givens 2013; Murphy et al. 2016; Ridoutt et al. 2020; Cifelli et al. 2022; White & Gleason 2023], and eggs [Rymer & Givens 2005; López Sobaler et al. 2017; Wallace & Fulgoni 2017; Iannotti et al., 2017; Lutter et al. 2018; Myers & Stevenson Ruxton 2023]. Several of these nutrients are not easily obtained from plants due to a lower content (or absence), lower bioavailability, and/or the presence of anti-nutritional factors [Zhang et al. 2016]. 

Although the omnivore spectrum allows flexibility with respect to animal/plant ratios, current consumption patterns indicate that most countries would need about 1/3 of the caloric intake from ASFs to achieve nutrient adequacy [Nordhagen et al. 2020]. Adopting diets within the range recommended by the EAT-Lancet Commission [i.e., ranging from vegan to quasi-vegetarian, with ASFs limited at 14% of the kcal intake; see elsewhere], requires either food fortification and/or nutrient supplementation to reach adult nutritional adequacy (especially with respect to zinc, iron, calcium, and vitamin B12). Alternatively, it would require an increase in nutrient-dense foods (fish, shellfish, seeds, eggs, beef) and reduced quantities of high-phytate foods (whole grains, pulses, nuts) [Beal et al. 2023]. To meet nonprotein nutrient-based recommendations without such interventions (other than B12), it has been estimated that about half of total protein should be animal-based [Vieux et al. 2022]. 

Reducing ASF intake below the thresholds mentioned above may undermine the supply of important 'nutrients of concern', which are already problematic and risk becoming even more so [Phillips et al. 2015]. Also, simply replacing these nutrients with plant-derived options tends to increase cost, food amounts, and total energy intake [Cifelli et al. 2022]. Replacement of ASFs with plant-based imitations [see elsewhere], may thus lead to deficiencies in key nutrients if the diet is not sufficiently adjusted, even when these products are fortified [Walther et al. 2022]. Moreover, even within the general omnivorous population, dietary intake data from the Netherlands show that fortification and supplementation only make a modest contribution to the adequacy of micronutrient intake [Bird et al. 2023].

In the most extreme case, vegan diets are followed, which in Homo sapiens is without evolutionary precedent [O'Keefe et al. 2022]. Even if omnivores also need to pay attention to various nutrients of concern, and although lower nutrient intake does not always result in lower biomarkers [Derbyshire 2017; Bakaloudi et al. 2021], removal of ASFs complicates the target of adequate essential nutrition at population level [Leroy & Barnard 2020]. It often concerns the foremost limiting micronutrients for nutrition security worldwide, which are best sourced from ASFs (e.g., iron, zinc, vitamins A, B12, and D; see below), even if some are more plant-associated (e.g., magnesium, folate) [cf. Nelson et al., 2018; Passarelli et al. 2022; Stevens et al. 2022]. 

Many plant foods, indeed, offer their own nutritional benefits. Although people following plant-based diets tend to have a lower intake and/or status of protein [discussed elsewhere], long-chain omega-3 fatty acids, iron, zinc, calcium, iodine, selenium, and vitamins A, D, and B12, they tend to eat more fibre, potassium, magnesium, folate, and vitamins C and E [Neufingerl & Eilander 2022, 2023; Dawczinsky et al. 2022; Koller et al. 2023]. This means that ASFs and plants are ideally combined to achieve optimal nutrient supply within the omnivore spectrum. Moreover, ASFs such as meat and fish also enhance the absorption of micronutrients from plant-based foods based on food matrix and diet matrix effects (the so-called "meat factor", which has been demonstrated for iron and zinc in particular) [Consalez et al. 2022]. 

Combined micronutrient issues have been reported in vegan or vegetarian populations of various countries [Larsson & Johansson 2002; Kristensen et al. 2015; Elorinne et al. 2016; Schüpbach et al. 2017; Balci & Goktas 2018; Chouraqui et al. 2020; García-Morant 2020; Menzel et al. 2021]. Vegan diets frequently cause predictable deficiencies in nutrients, and may increase the risk for bone fractures, sarcopenia, anaemia, and depression on the long term [O'Keefe et al. 2022; Zheng et al. 2023]. A meta-analysis (48 studies) looking into the adequacy of vegan diets indicated that they tend to parallel low intakes of protein [discussed elsewhere], certain vitamins (B2, B3, B12, and D), and certain minerals (iodine, zinc, calcium, potassium, and selenium), which may result in deficiencies of vitamin B12, zinc, calcium, and selenium [Bakaloudi et al. 2021]. Multiple nutrient deficiencies can even be obtained when adopting mass-marketed well-planned whole-food vegan meal plans, such as the ones promoted by Forks over Knives [Graham et al. 2023].

 

Below, a list of important nutrients that are typically associated with ASFs is provided. People that choose to avoid ASFs are advised to look into suitable alternatives and/or supplements to minimize risks. It is also important to bear in mind that the ability to subsist for prolonged periods on vegetarian diets differs at the interindividual level due to variations in genetic make up, for instance at the level of fat metabolism and brain function [Yaseen et al. 2023]. In any case, diets that heavily restrict or avoid ASFs should prioritize nutrient-dense plant foods [Asfura-Carasco et al. 2022], because they may otherwise result in a nutritional fitness that is relatively weaker [Kim et al. 2018]. In the latter case, an increase the risk for deficiencies should be expected, especially in the (very) young. The Vegan Federation of France, for instance, recommends supplementation with vitamins B2, B6, B12, D3 (from lichen), folic acid, selenium, and iodine [Federation Végane 2021]. In the review article 'Vegan nutrition: a preliminary guide for health professionals' [Koeder & Perze-Cueto 2022], several potential nutrients of focus were listed, including protein [discussed elsewhere], vitamins A and B12, omega-3 fatty acids, and various minerals (iron, zinc, calcium, iodine, and selenium). 

 
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Long-chain omega-3 fatty acids (EPA/DHA)

Long-chain omega-3 fatty acids (EPA, DHA) play a role in immunity and in neuronal, retinal, and cardiovascular health. They are predominantly found in oily fish, meat, and eggs. While a precursor is present in plants, its conversion rate is limited. Dietary intake of these fatty acids tends to be low, resulting in a diminished in vivo status, especially notable in people adhering to plant-dominated diets, by choice or necessity, and critical in the young. It is not always straightforward to significantly improve someone's DHA status with supplementation of ALA or even EPA.

Further reading (summary of the scientific literature): 

The long-chain omega-3 fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) are critical for immunity as well as neuronal, retinal, and cardiovascular health [Ruxton et al. 2004; Innis 2008; Coletta et al. 2010; Calder 2012, 2015; Swanson et al. 2012; Dyall 2015; Whelan et al. 2016; Shahidi & Ambigaipalan 2018], with benefits for brain development and function, mental health, and memory [Osher & Belmaker 2009; Sinn et al 2012; Bentsen 2017; Alex et al. 2019].

 

Fish, meat, and eggs are the predominant sources of EPA and DHA in common diets, with oily fish being a particularly good option. Algal oil seems a suitable alternative to meet DHA requirement for people avoiding ASFs [Arterburn et al. 2008], but it is important to bear in mind that most supplements are oxidized beyond the acceptable threshold [Hands et al. 2023]. Except in the case of regular fish consumption, intake in most Western societies and populations is below the intake level of 250-400 mg/d recommended by some authors (Howe et al. 2006; Givens & Gibbs 2008; Sioen et al. 2013). As a result, low EPA and DHA blood levels are found worldwide, both in the West and in low- and middle-income countries, while high levels are found in such areas as Japan, Scandinavia, and regions that have not yet been adapted to Westernized food habits [Stark et al. 2016].

 

The precursor of the long-chain omega-3 fatty acids, alpha-linolenic acid (ALA), is present in plants. Although ALA is in principle to be seen as the only essential omega-3 fatty acid in human diets, its further conversion rate in to EPA and DHA can be a limiting factor for health (anywhere between 0.2-21% for conversion into EPA and 0-9% for DHA; Davis & Kris-Etherton 2003; Burdge & Calder 2005; Brenna et al. 2009; Cholewski et al. 2018). Preformed DHA in the diet of omnivores explains its higher proportion in the blood and tissue lipids compared with vegetarians, even if ALA intake is equal or greater [Sanders 2009]. Improvement of blood DHA status is difficult to achieve with supplementation of ALA or EPA precursors [Brenna et al. 2009]. Although 5 mg/d of DHA is a minimum for brain requirements, much higher daily intakes of have been suggested for neurocognitive benefits (>1 g EPA + DHA) [Yurko-Mauro et al. 2015] and cardiovascular protection (0.5 g) [Givens & Gibbs 2008], although the latter may only be valid for even much higher levels (>4 g) [Tsoupras & Zabetakis 2020]. Whereas total omega-3 or -6 intake had no effect, higher intake of DHA or canned tuna was associated with longer leukocyte telomere length in US males, suggestive of less oxidative stress and inflammation [Seo et al. 2022].

 

Typically, vegan diets are devoid of DHA and even lacto-ovo-vegetarian diets tend to only provide around 20 mg/d of DHA [Sanders 2009]. Achieving 250 mg/d would require 2-5 g or 5-12 g of ALA per day for EPA and DHA, respectively. Yet, American vegetarians and vegans consume less than 1 g ALA per day [Welch et al. 2010], which is reflected in lower DHA levels [Sanders 2009]. It is no surprise, therefore, that EPA/DHA intake and serum levels are often lower in vegetarians and vegans [Dawczinsky et al. 2022; Gogga et al. 2024]. British vegetarian males have about 30% lower levels of EPA and DHA than omnivores, while in vegans this is about 50% lower [Rosell et al. 2005]. Young vegan men have been shown to display a higher status of ALA but lower EPA and DHA levels in plasma, erythrocytes, and spermatozoids [Chamorro et al. 2020, 2023]. Populations most likely at risk of EPA/DHA deficiency are new-born and weanling infants, or children and adolescents in areas of dryland agriculture [Sinclair et al. 2022].

 
Vitamin A (retinol)

Vitamin A (retinol) plays a role in cell and tissue differentiation, immunity, and the health of the eyes and skin. It is abundantly found in animal source foods, particularly in liver. Some plants contain precursors (carotenoids), but their conversion may be inefficient. The biological value of carotenoids is genetically contingent and influenced by the carotenoid species, dietary context, and fat intake. Vegans and vegetarians, especially those with poor converter phenotypes, may be at risk of vitamin A deficiency and should monitor their intake and status. Vitamin A deficiency can lead to increased susceptibility to infections, impaired night vision, corneal damage, and blindness, especially in young children. 

Further reading (summary of the scientific literature): 

The most important function of vitamin A is the control of cell differentiation and turnover, having effects on growth regulation, tissue differentiation, and skin and eye health. Deficiency leads to increased susceptibility to infections, impaired night vision, corneal damage, and blindness (especially in pre-school children). 

 

The vitamin is found in ASFs, in particular liver but also eggs, cheese, and meat [Darwish et al. 2016]. In Australian lamb, the liver had more vitamin A (but also folate and vitamin B12) than the carcase and other co-products combined [Wingett & Alders 2023]. Plants, in contrast, do not contain vitamin A as such, but often have abundant levels of precursors (carotenoids). The latter, however, are rather poorly absorbed and converted [Solomons & Bulux 1993]. For β-carotene, absorption and conversion vary between 5-65% and 4:1-28:1, respectively [Tang 2010; Haskell 2012]. 

 

The biological value of carotenoids depends on ethnic and genetic variability, with 32-69% lower β-carotene-into-retinol conversion in the case of BCO1 mutations (prevalent in 40% of Europeans but somewhat less in Asians) [Leung et al. 2009; Lietz et al. 2011; Borel & Desmarchelier 2017]. Other factors that affect the biological value are the dose [Deming & Erdman 1999; Novotny et al. 2010; Priyadarshani 2017], as well as the carotenoid species ingested and the dietary context [Deming & Erdman 1999; Tanumihardjo et al. 2002; Green & Fascetti, 2016; Boonstra et al. 2017; Priyadarshani 2017]. 

 

For instance, dietary carotenoids that do not function as substrates (e.g., canthaxanthin and zeaxanthin) inhibit carotene dioxygenase and reduce the proportion that is converted into retinol [Bender 2002]. Furthermore, in diets providing <10% of energy from fat, the absorption of both retinol and carotene is impaired. Absorption thus fails when carotinoid-rich plants are consumed with fat-free salad dressing [Brown et al. 2004], while the type of fat and emulsification in the dressing also matter considerabley [Yao et al. 2023]. Lastly, protein-energy malnutrition affects plasma levels of circulating retinol-binding protein, leading to deficiency even if there are adequate intake levels and reserves in the liver.

 

Although also relevant for omnivore populations [Bird et al. 2023], vegans and vegetarians may particularly benefit from monitoring their vitamin A intake and status, as these can be insufficient [Chełchowska et al. 2003; Pal & Sagar 2007; Kristensen et al. 2015; Seves et al. 2017; Menzel et al. 2021; Huang-Link et al. 2021]. This requires particular attention in the case of 'poor converter phenotypes' [Leung et al. 2009].

 

Vitamin B12 (cobalamin)

Vitamin B12 is a critical nutrient for neural health, DNA production, and red blood cell formation. Deficiencies can lead to irreversible nerve damage. The vitamin is found in animal source foods only. Despite advice to supplement, many vegetarians and vegans remain deficient in B12, which is particularly worrying in the case of pregnant and lactating women, infants, and children. Concerns about lower B12 levels are justified based on population-level observations, and deficiencies are often overlooked or misdiagnosed. 

Further reading (summary of the scientific literature): 

The largest concern in vegan diets is related to cobalamin (B12), which is necessary for neural health and the production of DNA and red blood cells [Green et al. 2017; Smith et al. 2018, Kramarz et al. 2023]. Deficiencies may lead to irreversible nerve damage, with infants and children being particularly vulnerable [see elsewhere]. Although hematologic abnormalities can be therapeutically corrected within weeks, neurologic symptoms may persist for months or years and become irreversible [Johnson 2022].

The vitamin is restricted to ASFs, with the arguable exception of uncommon foods such as nori. Despite popular claims, edible blue-green algae (e.g., spirulina) predominately contain inactive corrinoids, i.e., pseudo-vitamins that interfere with the bioavailability of the actual vitamin [Watanabe et al. 1999, 2013]. Algae and other alternative sources such as kombucha or other fermented products should not be considered as adequate [Zugravu et al. 2021]. Generally, plant foods have either minute amounts due to rhizobium bacteria or are contaminated by (human) faeces [Herbert 1988]. Although lake water containing algae can provide B12 [Daisley 1969], it is unrealistic to be based on this as it would require 2-20 liter to reach the RDA. Taken together, non-ASF sources cannot provide B12 in reasonable proportions. A 12-weeks intervention trial has indicated that the partial replacement of animal source foods with plant protein foods decreases the intake and status of B12 [Pellinen et al. 2022]. 

 

Groups at risk of B12 deficiency include vegans, vegetarians, older adults, and individuals with limited diets [Abuyaman et al. 2024]. Avoidance of ASFs requires supplementation or fortification with vitamin B12, even if there is some discussion on the contribution of the human colon [Kurpad et al. 2023]. In the absence of such dietary supplementation, severe deficiency and irreversible harm will usually eventually develop in vegan individuals [Pelling et al. 2022]. According to some, the supplement for food fortification (cyanocobalamin) could be unreliable [Obersby et al. 2013]. However, results depend on the frequency of administration and sufficient levels can be reached when properly administrated, whereby cyancobalamin tends to give better results than the methylcobalamin variant [Zugravu et al. 2021]. In contrast, many ASFs are potent providers of vitamin B12. A 100-g serving of beef, tuna, trout, or sardines contains >100% of the recommended daily intake; a similar amount of liver, kidney, or clams will even provide >1,000% [Semeco 2018]. Dairy contains somewhat lower levels but is still an excellent source, leading to better absorption than other ASFs [Vogiatzoglou et al. 2009]. Fluid milk even seems to provide sufficient vitamin B12 to meet the needs of >60% of the global population [White & Gleason 2023].

 

Despite widespread advice to supplement and monitor, vegetarians and vegans are often in the deficient or borderline-deficient range [Hermmann & Geisel 2002; Dawczinsky et al. 2022], which is also the case for children and adolescents on vegan and macrobiotic diets [Jenssen 2022]. In the UK, the current recommended intake (1.5 µg/d) may not adequately consider the vitamin B12 deficit in populations consuming 'plant-based' diets, given that 4-20 µg/d is more appropriate to prevent deficiency across the life-course [Niklewicz et al. 2022]. One on three British vegan users of self-selected supplements still remained below the lower reference nutrient intake, compared to 80% of the non-supplemented vegan population [Lightowler & Davies 2000]. Similarly, 39% of Australian vegan females had an inadequate total intake of vitamin B12, with one fourth not taking any supplements and - among those supplementing - almost one on four not supplementing adequately [Benham et al. 2022]. In a German study, fewer lacto-ovo-vegetarians (51%) used B12 supplements compared to vegans (90%), which led to a lower B12 status in the former [Storz et al. 2023].

Concern about lower B12 levels is warranted by observations at population level [Alexander et al. 1994; Herbert, 1994; Hokin & Butler 1999; Donaldson 2000; Larsson & Johansson 2002; Elmadfa & Singer 2009; Obersby et al. 2013; Pawlak et al. 2013, 2014, 2015; Woo et al. 2014; Naik et al. 2018; Singla et al. 2019; Bakaloudi et al. 2021; Fusano et al. 2020]. It has been estimated that 17-39% of vegetarian and vegan pregnant women in lower socioeconomic countries are vitamin B12-deficient [Pawlak et al. 2014]. In the UK, average daily B12 intake was estimated to be a mere 0.4 µg in vegans, compared to 7.2 µg in meat-eaters [Davey et al. 2007]. Therefore, half of the British vegan males were shown to be deficient based on serum values of B12, compared to 7% of their vegetarian and none of their omnivore counterparts [Gilsing et al. 2010]. When using more sensitive diagnostics for deficiency at cellular level (holoTC and MMA), >90% of vegans and >70% of vegetarians turned out to be deficient, compared to 10% of omnivores [Hermann et al. 2003a,b, 2005]. Unfortunately, cases of deficiency are often overlooked or misdiagnosed [Wolffenbuttel et al. 2019]. However, with adequate supplementation, the vitamin B12 status in healthy vegans can be similar to that of healthy omnivores [Storz et al. 2023].

B vitamins (other than B12)

Among the B vitamins, other than vitamin B12, vitamins B1 (thiamine), B2 (riboflavin), and B3 (niacin) stand out as potentially limiting in diets that contain low amounts of animal source foods. While these vitamins are present in various plants, they may become a concern in inadequately developed diets, especially for populations heavily dependent on cereals and living in poverty. Thiamine, which is found in a variety of foods of plant and animal origin, is essential for energy metabolism, and its deficiency leads to beriberi. While beriberi is now rare, it can occur in people on low-nutrient diets high in refined carbohydrates or with high alcohol intake. Riboflavin is crucial for oxidation and reduction reactions in metabolism, especially energy metabolism. While plant foods contain riboflavin, dairy is a major source, providing sufficient riboflavin for about half of the global population. Vegans may sometimes have lower riboflavin status, and deficiency in pregnant women can lead to consequences for newborns. Niacin deficiency, known as pellagra, was historically associated with diets low in animal source foods. Niacin can also be obtained from tryptophan in the diet, but its availability may be limited in protein-poor diets. Niacin deficiency can lead to neurological conditions and impaired immunity.

Further reading (summary of the scientific literature): 

Vitamin B1 (thiamine) plays a role in energy metabolism and its deficiency leads to beriberi. The latter is now rarely a problem, except occasionally for people on low-nutrient diets that are very high in refined carbohydrates, as seen with Japanese adolescents in the 1980s, or with high alcohol intake. High polyphenol intake (e.g., tannic acids in tea and betel nuts) also may interfere with bioavailabilty [Bender 2002].  Vitamin B1 is found in whole grains, nuts, and legumes; good ASF sources are meat (especially pork and liver), eggs, and fish.

 

Vitamin B2 (riboflavin) plays a role in oxidation and reduction reactions in metabolism at large, and energy metabolism in particular. Although also present in plant foods (green vegetables, mushrooms, nuts, etc.), ASFs are major dietary sources of vitamin B2. This holds particularly true for dairy (often >25% of intake), with the average riboflavin status reflecting milk consumption to a considerable degree in different countries [Bender 2002]. Globally, fluid milk provides sufficient riboflavin to meet the needs of half of the population [White & Gleason 2023]. The vitamin is sometimes mentioned as problematic when avoiding ASFs [Larsson & Johansson 2002; Seves et al. 2017; Menzel et al. 2021; Jaeger et al. 2022; Kramarz et al. 2024], being deficient in 30% of Austrian vegans, compared to 10% of the omnivores and vegetarians [Majchrzak et al. 2006].

 

Vitamin B3 (niacin) [Ng & Neff 2018], of which the deficiency (pellagra) was described over a century ago for diets low in ASFs [Morabia 2008], is still not sufficiently available to billions of cereal-dependent poor, often misdiagnosed as 'environmental enteropathy' or stunting [Williams & Hill 2019]. Deficiency is not an issue when the metabolism of its precursor tryptophan is functional, but can be created due to a lack of dietary tryptophan in protein-poor diets combined with low niacin intake as such. In cereals, niacin is bound as niacytin which makes it biologically unavailable unless it is released with specific alkaline treatments (as for traditional maize tortillas in Mexico). Niacin may have acted as a key brain-thropic element of ASFs during evolution [see elsewhere] and its inadequate supply may lead to 'de-evolutionary' brain atrophy [Williams & Dunbar 2013; Williams & Hill 2017a,b]. Deficiency causes the neurodegenerative condition pellagra and may impair resistance to acute infections [Williams & Hill 2019]. 

Vitamin K2 (menaquinones)

Vitamin K2 participates in the synthesis of blood clotting factors in the liver, as does vitamin K1. However, its biological relevance is more important, given its role in brain function and bone health, and in the prevention of cardiometabolic diseases. Vitamin K2 is found in animal source foods and in some fermented plants. Full-fat dairy products serve as rich sources. Some vegetable fats and oils may potentially interfere with vitamin K2-dependent processes. More research is needed to fully understand the specific benefits of vitamin K2.

Further reading (summary of the scientific literature): 

Vitamin K plays a role in blood clotting (K1 and K2), as well as brain function, bone health, skin health, and cardiovascular health (K2) [Hauschka 1986; Schurger et al. 2007; Theuwissen et al. 2012]. The K1 and K2 variants may thus have to be seen as separate nutrients [Beulens et al. 2013; Schwalfenberg 2017; Akbulut et al. 2020]. For instance, the MK-4 form of vitamin K2 reduces blood vessel calcification, whereas vitamin K1 does not [Spronk et al. 2003]; vitamin K2, but not vitamin K1 has been associated with a reduced risk of coronary heart disease [Geleijnse et al. 2004; Hariri et al. 2021] and  prostate cancer [Nimptsch et al. 2008], especially MK-7, MK-8 and MK-9 [Gast et al. 2009]. 

 

Vitamin K1 is mostly obtained from plants, whilst vitamin K2 is typically obtained from ASFs (e.g., cheese, egg yolk, butter, liver, meat, salami) and some fermented plant foods (e.g., natto, sauerkraut) [Elder et al. 2006]. The content of vitamin K2 is especially high in dairy products, proportional with the fat content [Fu et al. 2017], which is useful in view of improved bone health and cardiovascular health [Geleijnse et al. 2004; Walther et al. 2013; Vermeer et al. 2018], for instance by improving glycemic indices of type-2 diabetic patients [Karamzad et al., 2020], doing so better than vitamin K1 [Li et al. 2018], controlling vascular calcification [Schurgers 2013], possibly improving mitochondrial function [Vos et al. 2012; Su et al. 2021] and  reducing cancer risk [Nimptsch et al. 2010]. Other good sources include egg yolks and offal [Booth 2012]. However, more research is needed to substantiate potential specific benefits of vitamin K2, for instance with respect to musculoskeletal health [Fang et al. 2012; Hamidi & Cheung 2014]. It has been suggested that some types of vegetable fats and oils may inhibit or alter vitamin K2-dependent processes [Hashimoto et al. 2014; Okuyama et al. 2016, 2018].

Calcium and vitamin D

Adequate intake of calcium and vitamin D is crucial for neuromuscular regulation, bone health, immune system function, and disease prevention. Excellent sources of calcium include fish with edible bones and dairy products. Plant-derived calcium may have reduced bioavailability, although good options exist. Vitamin D is best obtained through sun exposure, complemented by the intake of oily fish, liver, and eggs. Vegans may require supplementation as vegan-friendly D2 supplements are less effective than D3 supplements from animal sources. Both calcium and vitamin D deficiencies are common in various populations, which may need particular care in vegans and vegetarians, and may lead to lower bone mineral density and increased risk of fractures.

Further reading (summary of the scientific literature): 

Sufficient calcium intake is needed for neuromuscular regulation and bone health, but relies on vitamin D which plays a role in its absorption and homeostasis. Calcium may potentially protect against a series of non-communicable diseases, such as colorectal cancer [Yang et al. 2019] and the metabolic syndrome, but results are mixed [NIH]. Co-ingestion of calcium and protein can potently stimulate GLP-1 increase, which in turn may beneficially affect insulin response and glucose metabolism, and promote satiety [Watkins et al. 2021]. Vitamin D also plays a role in disease prevention, and is involved in the immune system [Prietl et al. 2013; Dancer et al. 2015; Martineau et al. 2017]. Moreover, it is a factor in cell proliferation and the secretion of insulin, parathyroid hormone, and thyroid hormone [Bender 2002], and is related to cognitive function, telomere length, and lower oxidative stress markers in older adults [Yang et al. 2020]. 

 

Calcium is easily obtained from fish with edible bones, as well as from dairy [White & Gleason 2023; NIH]. Sufficient intake from plant foods, such as spinach, is complicated by a reduced bioavailability due to oxalate, phytate, tannin, and fibre [Amalraj & Pius 2015; Al Hasan et al. 2016] In such cases, impractical multiple servings may be needed to match a single portion of dairy [Weaver et al. 1999]. However, cruciferous vegetables that contain low contents of mineral-complexing factors can be good sources of bioavailable calcium, even if amounts of calcium per serving are lower than for dairy [NIH]. This is, for instance, the case for broccoli and kale [Muleya et al. 2024], and for various selected indigenous leafy vegetables in Africa, Asia, and Latin America [Amalraj & Pius 2015; Castro-Alba et al. 2019; Gowele et al. 2019]. 

 

The best source of vitamin D (cholecalciferol) is sun exposure, while dietary sources are few (mainly oily fish, eggs, liver, and butter). Moreover, vegan-friendly D2 supplements are less effective than D3 supplements (which are commonly obtained from animal sources, although lichen can also serve as a source) [Wilson et al. 2017; Zhang et al. 2019]. Meat provides only low quantities of vitamin D, but is nonetheless a valuable source, as it is mostly present as calcitriol, i.e., the final active metabolite, many-fold more potent than cholecalciferol) [Bender 2002]. In Finnish adolescents, vitamin D intake was mainly driven by intake of supplements and milk products, followed by consumption of meat products, travels to sunny countries, and average daylight time [Soininen et al. 2022]. A fourth of these adolescents did not meet the recommended level (10 µg/d) and almost a third had too low serum levels.

Suboptimal calcium and/or vitamin D levels are often encountered at population level, also for omnivores [Bird et al. 2023]. Yet, vegetarian and especially vegan populations are particularly vulnerable, compared to omnivores [Dawczinsky et al. 2022; Bickelmann et al. 2023]. This is especially the case because the intake of Ca-fortified foods and vitamin D supplements can often be suboptimal in these populations [cf. Swiss vegans: Bez et al. 2024]. This is all the more crucual in northern latitudes with little sunlight exposure [Ambroszkiewicz et al. 2010; Ströhle et al. 2011; Clarys et al. 2014; Kristensen et al. 2015; Elorinne et al. 2016; Hansen et al. 2018; Bakaloudi et al. 2021; García-Morant 2020; Huang-Link et al. 2021; Teotia et al. 2021], even with supplements [Larsson & Johansson 2002; Lachowicz & Stachón 2022]. Deficiency may often also be a multi-nutrient issue [Menzel et al. 2021; Ogilvie et al. 2022]. This mirrors lower 25(OH)-D levels, lower bone mineral densities, and higher bone turnover and fracture rates [Chiu et al. 1997; Appleby et al. 2007; Iguacel et al. 2018, Hansen et al. 2018; Zheng et al. 2023]. Higher hip fractures rates in vegans/vegetarians compared to meat eaters can be partially attenuated with adjustment for dietary calcium and/or total protein, but not to the full extent [Tong et al. 2020]. In the Adventist Health Study 2, female vegans had a 55% higher risk of hip fracture than nonvegetarians, requiring supplementation with calcium and vitamin D [Thorpe et al. 2021].

(Haem) iron

Iron is essential for blood health, the endocrine system, and proper development. Excellent sources include red meat and liver, whereas plants have reduced bioavailability. Even with higher total iron intake, vegetarian diets may result in lower iron status. In high-income countries, iron-deficiency is on the rise, especially among females and likely due to dietary changes, such as a decline in red meat intake. Avoiding animal-source foods requires specific practices like sprouting, fermentation, and soaking legumes, as well as consuming vitamin C-rich drinks instead of tea and coffee to improve iron absorption. Adequate levels of vitamin A and riboflavin are also necessary for iron mobilization and haemoglobin synthesis. Interestingly, the absorption of nonheme iron from plants can be enhanced when consumed with meat or fish, possibly due to certain compounds released during digestion of muscle tissue.

Further reading (summary of the scientific literature): 

Iron is needed for blood health, endocrine functioning, and proper development. Early life iron deficiency risks impairing brain development [Antonidis et al. 2015]. Iron absorption from plants is limited because of inhibitors (e.g., phytates and polyphenols), but enhancers can also be present (e.g., vitamin C) [van Wonderen et al. 2023]. The EAT-Lancet diet, for instance, falls short on iron, which has been related to the high levels of phytates [Beal et al. 2023]. Iron status generally correlates with meat and fish intake but not necessarily with total iron intake (often driven by cereals) [Lavriša et al. 2022]. Even if vegans and vegetarians have intakes above the recommendation levels, and often higher than those of omnivores, this may still result in lower iron status [Alexander et al. 1994; Wilson & Ball 1999; Waldmann et al. 2004; Wongprachum et al. 2012; Gibson et al. 2014; Awidi et al. 2018; Śliwińska et al. 2018; Chai et al. 2019; Fusano et al. 2020; García-Maldonado et al. 2023], with women being particularly vulnerable [Dawczinsky et al. 2022].

In the US, increased iron deficiency anaemia and related mortality rates between 1999 and 2018 were likely related to a decline in dietary iron intake resulting from an iron concentration decline in US food products and a shift in dietary patterns [Sun & Weaver 2021]. The latter included a 15% decrease in beef intake and a 22% increase in chicken intake. Women are particularly affected, which is a major public health concern in the case of maternal undernutrition [see elsewhere]. Between 2004 and 2016, iron deficiency in US women increased from 13% to 20% [Mei et al. 2021]. Too low intake has also been reported in other countries, such as the Netherlands [Bird et al. 2023]. 

Avoiding ASFs requires enhanced attention to specific practices such as sprouting, fermentation, soaking of dried legumes before cooking, and replacement of tea and coffee at meals with vitamin C-rich drinks. The presence of phytates may compromise bioavailability [Al Hasan et al. 2016]. Also, sufficient levels of both vitamin A and riboflavin are required for iron mobilization and hemoglobin synthesis. When the latter two micronutrients are limiting, iron intake alone may be insufficient to treat anaemia [Allen 2005]. Interestingly, an enhancement of the absorption of nonheme iron from plants is seen when they are consumed together with meat or fish. The mechanism is not clear but seems to work independently from the presence of haem in ASFs and may instead be driven by peptides, phospholipids, and/or mucopolysaccharides that are released during digestion of muscle tissue, mediating the formation of absorbable ferric oxohydrate nanoparticles [Consalez et al. 2022]. 

Zinc

Zinc is required for a healthy immune system, correct DNA synthesis, healthy growth during childhood, fertility, and wound healing. Zinc deficiency results in compromised immunity, delayed puberty, and cardiometabolic risk. The best sources are meat, poultry, and fish, while vegetarian diets can reduce absorption by up to one-third. When plants are combined with animal-derived foods, absorption improves. Diets low in animal source foods and rich in fibre and phytates cause low zinc status, even at recommended intake levels. Yet, even in omnivorous populations, zinc intake levels can be below the estimated average requirement.

Further reading (summary of the scientific literature): 

Zinc is the prosthetic group of >100 enzymes and is involved in the receptor proteins for steroid and thyroid hormones, calcitriol (vitamin D), and retinol (vitamin A) [Bender 2002]. It is required for a healthy immune system, correct DNA synthesis, healthy growth during childhood, fertility, and wound healing. Low levels are associated with delayed puberty and impairment of taste and smell. It also may lead to cardiovascular risk in predisposed subjects [Soinio et al. 2007]. Treating suboptimal zinc levels results in improved glycaemic control, especially in subjects with diabetes [Wang et al. 2019]. 

 

In contrast to iron, zinc is less easily obtained from fortified foods [Gibson et al. 2014]. Whereas the best sources of zinc are meat, poultry, and fish, vegetarian diets reduce zinc absorption by one third [Hunt 2003]. As for iron, meeting the recommended intake is no guarantee for adequate zinc status [Tucker 2014]. Also, zinc absorption from plants improves when they are consumed together with ASFs, such as meat and fish. The mechanism is unknown but is likely attributable to the protein source [Consalez et al. 2022]. 

Based on the above, zinc intake can become potentially problematic when avoiding ASFs [Freeland-Graves et al. 1989; Foster et al. 2013; Gibson et al. 2014; Seves et al. 2017; Bakaloudi et al. 2021; Menzel et al. 2021; Dawczinsky et al. 2022; Klein et al. 2023]. Deficiency is often found among people living in (sub)tropical regions where unleavened wholemeal bread is a staple and zinc is bound to fibre and phytates [Bender 2002]. But even in Western omnivorous populations, zinc intake levels can be below the estimated average requirement [Bird et al. 2023].

Iodine

Iodine is essential for thyroid hormone synthesis, which may be compromised in diets that contain high levels of goitrogenic foods or have become more Westernized. Fish, seafood, seaweed, eggs, and dairy are good dietary sources. Dietary change to more plant-based diets could aggravate iodine adequacy, especially in regions without iodine fortification programmes. Deficiency leads to goitre, low metabolic rates, and mental retardation. This is particularly critical for lactating females. Vegetarians and vegans in such countries are at increased risk of low iodine status and deficiency, and may need iodine supplements to ensure adequate intake. 

Further reading (summary of the scientific literature): 

Iodine is required for the synthesis of the thyroid hormones, leading to goiter, low metabolic rates, and mental retardation in the case of deficiency. The latter is exacerbated in the case of co-occurring selenium deficiency. Dietary sources of iodine include fish, shrimp, seaweed, and eggs. Dairy is also a particularly good source [van der Reijden et al. 2017], with milk delivering almost half of the iodine intake in Ireland [McNulty et al. 2017]. Although iodized salt and staple foods improve the situation at population level, sufficient intake is still one of the main nutritional challenges [Andersson & Braegger 2022].

 

Changing dietary behaviour can have an important impact on iodine status, even in regions with a historical record of iodine adequacy. For instance, inhabitants of the Faroe Islands have been iodine replete with traditional diets, rich in fish and whale meat, but are now facing the risk of deficiency as diets become more Westernized [Líggjasardóttir Johannesen et al. 2023]. The problem is acerbated by Western dietary change away from iodine-rich foods, especially in countries where iodine fortification is absent. Lower dairy consumption provides such example. In the UK, declining milk intake over the last 50 years leads to deficiency risk, especially amongst women, children and teenagers [Woodside & Mullen 2020]. In Israel, otherwise iodine-rich milk and dairy products only generate 22% of the recommended daily allowance due to the low consumption levels, and even less so in poor subgroups [Ovadia et al. 2018]. Even in Ireland, a diary stronghold, iodine intake is adequate on average, but nonetheless below the estimated average requirement for 1/4 of the population [McNulty et al. 2017], and particularly elevated in women of childbearing age [Nawoor et al. 2006; McNulty et al. 2017]. 

In general, a shift to more 'plant-based' eating in the West could potentially worsen the problem, especially in countries without universal salt iodization. A lower iodine status and higher deficiency risk have been shown for vegetarians and, particularly, vegans through systematic review and meta-analysis [Eveleigh et al. 2023]. In various Western countries, iodine tends to be more limiting in diets that restrict ASFs [Krajcovicová-Kudlácková et al. 2003; Leung et al. 2011; Kristensen et al. 2015; Brantsæter et al. 2018, Fallon & Dillon 2020; Groufh-Jacobsen et al. 2020; Menzel et al. 2021; Nicol 2023; Zaremba et al. 2023], particularly in countries that already have a high prevalence of iodine deficiency [Eveleigh et al. 2020]. Partially replacing animal source foods with plant protein foods in a Finish intervention trial was shown to decrease the intake and status of iodine [Pellinen et al. 2022]. In the UK, exclusive consumers of plant-based alternatives were classified as iodine deficient compared to consumers of milk, who were iodine sufficient on average [Dineva et al. 2020]. Because iodine concentrations in such alternatives are an order of magnitude lower than in actual dairy, it has been argued that British consumers of plant-based alternatives should use iodine fortified products or iodized salt for home cooking [Alzahrani et al. 2023; Nicol 2023]. In Australia, both women consuming an omnivore and vegan diet were characterized by suboptimal iodine levels, but this was more pronounced in the latter group [Whitbread et al. 2021]. In the US, iodine status is sufficient at the population level but varies widely across the population, despite the use of iodized salt [Niwattisaiwong et al. 2017]. One US study reported that iodine concentrations of breast milk may be inadequate in most lactating females, with highest incidence in the samples coming from vegan subjects [Pawlak et al. 2023]. Because vegan and vegetarian mothers are at risk of reduced iodine concentrations in their milk, iodine supplements are recommended [LactMed 2023].

Dietary change can also create challenges when the intake of goitrogenic foods is increased (e.g., cabbage, kale, turnips). These foods may compromise thyroid function, despite normal iodine intake. This is unproblematic with normal consumption patterns or when these foods are cooked, but it can be an issue at large intake levels (e.g., kale-containing smoothies). Prior to iodide enrichment of flour at the beginning of the 20th century, goiter was seen even in the coastal country of The Netherlands, probably due to large amounts of fermented cabbage in the traditional diet [Bender 2002]. 

Although iodine supplementation is beneficial for people with otherwise too low intake, this needs to be done with care. Too high intake comes with its own health problems. Also, the use of kelp powder or tablets in vegan populations may result in elevated thyroid stimulating hormone concentrations [Key et al. 1992]. 

   

Selenium

Selenium is involved in antioxidant defences, thyroid function, and immunity. Good sources are seafood, organ meats, dairy, nuts, and grains. Selenium availability in food relies on the content in soils, which affects plants more than animals. Intake may be low in some populations, such as older adults and vegan women. Avoiding animal source foods may reduce selenium intake and/or status. Deficiency risks may be higher in vegan and vegetarian populations, depending on the biomarkers used to identify deficiency. Excessive intake can also be toxic.

Further reading (summary of the scientific literature): 

Selenium is essential to good health because of its role in antioxidant defenses (glutathione peroxidase), thyroid function (thyroxine deiodinase), and immunocompetence, in particular against viral infections [Harthill 2011]. Deficiency also affects n-6/n-3 fatty acid metabolism [Schäfer et al. 2004]. Selenium, however, can also be toxic even in modest excess. Seafood and organ meats are the richest food sources of selenium, besides muscle meats, grains, and dairy [Fairweather-Tait et al. 2010]. Its availability in plants depends on the amount of selenium in the soil, whereas fluctuations in ASFs are less pronounced. 

 

Intake is declining in certain populations, as is the case for Australia where elderly are particularly at risk of low selenium status [Lymbury et al. 2008], or in vegan women in the UK, where the combination with low iodine threatens thyroid health [Fallon & Dillon 2020]. For German 1-3 year olds, intake was estimated as inadequate for 36-39% for the vegans and vegetarians, compared to 16% of the omnivores [Weder et al. 2022]. Avoiding ASFs may considerably reduce selenium intake and/or status [Schultz & Leklem 1983; Kadrabová et al. 1995; Rauma et al. 1995; Judd et al. 1997; Kristensen et al. 2015; Elorinne et al. 2016; Bakaloudi et al. 2021; Dawczinsky et al. 2022; Klein et al. 2023], even when including dietary supplements [Lightowler & Davies 2000; Larsson & Johansson 2002]. However, identifying deficiency in vegan or vegetarian populations depends on the biomarker used [Hoeflich et al. 2010], for instance when using selenoprotein P instead of total serum selenium [Menzel et al. 2021].

Choline

Choline contributes to neural health, memory, and foetal brain development, offering protection in early and later life. Since the liver's production of choline is insufficient, it must be acquired from the diet. Rich dietary sources include organ meats and eggs. Many, if not most, vegetarians may not meet the recommended intake levels, which is particularly relevant for pregnant women. In older adults, decreased choline intake and low circulating choline levels are associated with an increased risk for cognitive decline and Alzheimer’s disease progression.

Further reading (summary of the scientific literature): 

Choline plays an important role in neural health, learning and memory, and is critical for the development of the foetal brain [Hasselmo 2006; Caudill et al. 2018]. Optimizing choline levels may offer neural protection in both early and later life [Derbyshire & Maes 2023]. Decreased choline intake and low circulating choline levels are associated with an increased risk for cognitive decline and Alzheimer’s disease progression [Judd et al. 2023]. In older adults, an intervention study with daily supplementation of cytidine diphosphate-choline caused improvements in memory function and cognitive performance [Nakazaki et al. 2021]. The nutrient must be directly obtained from the diet since endogenous production as phosphatidylcholine in the liver is insufficient to meet the requirements. The situation is further complicated by genetic polymorphisms which may make certain individuals more predisposed to choline deficiencies [da Costa et al. 2006].

 

Organ meats and eggs are particularly rich in choline [Sanders & Zeisel 2007; NIH 2022]. Even if meat, poultry, and seafood consumption increases choline intake compared to non-consumers, it is by eating eggs that adequate choline levels can be met most easily [Wallace & Fulgoni 2017; Papanikolaou & Fulgoni 2023]. Because choline is found predominantly in ASFs, vegetarians and vegans may be at a greater risk of inadequacy [Wallace et al. 2018]. In an estimate for the USA, 9 on 10 people were found to be below 'adequate intake' (AI), with females consuming less choline than males across all age groups  [Wallace et al. 2016]. Similarly, 93% of pregnant women in Germany achieved inadequate choline intake (<480 mg/d), with odds of inadequacy being higher in the vegan/vegetarian subpopulation [Roeren et al. 2022]. 

Other bioactive compounds

Food offers more than the sum of protein, vitamins, and minerals, leading to a 'matrix effect', something which may at least be partially ascribed to the presence of overlooked biochemical compounds. Animal source foods contain various bioactive molecules, such as taurine, creatine, carnosine, anserine, carnitine, conjugated linoleic acid, insulin-like growth factor-1, and bioactive peptides. Their health effects are multiple, including antioxidant, anti-inflammatory, and anti-aging outcomes. They contribute to gastrointestinal, cardiovascular, and cognitive health, as well as immune functions.

Further reading (summary of the scientific literature): 

Food offers more than the sum of protein, vitamins, and minerals, leading to what some authors have called a 'matrix effect' in the case of dairy [Thorning et al. 2017; Astrup et al. 2019; Mozaffarian 2019; Timon et al. 2020], and what may at least be partially ascribed to the presence of overlooked nutrients. 

 

Meat, for instance, contains a series of bioactive molecules that are absent from plants, such as taurine, creatine, carnosine, and anserine. They have roles in anti-oxidative, anti-inflammatory, and anti-aging reactions and display muscular, retinal, immunological, cardiovascular, and/or neurological functions [Purchas et al. 2004; Williams 2007; Everaert et al. 2011; Ripps & Shen 2012; Barbieri et a. 2016; Ghodsi & Kheirouri 2018; Wu 2020; Kaviani et al. 2020]. Cognitive health, in particular, depends on carnosine [Hipkiss 2007; Babizhayev & Yegorov 2015; Yamashita et al. 2018; Sugihara et al. 2019] and creatine [Rae et al. 2003; Benton & Donohoe 2011; Smith et al. 2014; Brosnan & Brosnan, 2016]. Taurine too, is involved in cognitive health, as well as offering a myriad of other benefits [Rana & Sanders 1986, Laidlaw et al. 1988; Jeejeebhoy et al. 2002; Wharton et al. 2004; Yamori et al. 2004; Zhang & Kim 2007; Schaffer et al. 2009; Yamori et al. 2009; Wójcik et al. 2010; Rikimaru et al. 2012; Ripps & Shen 2012; Menzie et al. 2013; Schaffer et al. 2014; Troncon Rosa et al. 2014; Ito et al. 2015; Jong et al. 2017; Shaffer & Kim 2018; Bkaily et al. 2019]. Taurine deficiency is a driver of aging and its supplementation is able to improve the health and life span in animal models [McGaunn & Baur 2023; Singh et al. 2023]. Other compounds of interest include conjugated linoleic acid [Wannamethee et al. 2018], carnitine [Cavallini et al. 2004; Mynatt 2009; Serban et al. 2016; Veronese et al. 2018; Dahash & Sankararaman 2021; Manninen et al. 2022], ubiquinone, and glutathione [Williams 2007]. Carnitine seems particularly interesting as a protective substance in view of cardiomyopathy and various non-communicable diseases [Wang et al. 2018]. In vegetarian populations, the (serum) levels of these compounds can be lower than for omnivores, as is the case for carnitine [Dahash & Sankararaman 2021].

 

Connective tissue and bones are good sources of 4-hydroxyproline, which contributes to healthy skin and bones as well as gastrointestinal health [Wu 2011, 2020]. They deliver glycine as well, which is not only a building block of collagen but also plays a role as neurotransmitter, in blood sugar regulation, and as a cytoprotective agent in glutathione production [Wu et al. 2004; Gundersen et al. 2005; Hernandes & Troncone 2009; McCarty & DiNicolantonio 2014].

 

ASFs thus contribute to the maintenance of endogenous antioxidant defenses, even in the absence of fruits and vegetables [Young et al. 2002; Møller et al. 2003; Peluso et al. 2018]. They also provide bioactive peptides, potentially offering a variety of physiological benefits [Bhat et al. 2015], and insulin-like growth factor 1 (IGF-1) [Nordhagen et al. 2020; Headey et al. 2024]. IGF-1 may improve growth in children [Tang 2018] and is associated with reduced cancer and mortality in elderly [Levine et al. 2014]. Some ASFs, especially dairy products and seafood, also contain bio-protective lipids that may lead to decreased platelet aggregation or neurological protection [Lordan et al 2017, 2019a, 2019b; Wang et al. 2021]. Ruminant-derived foods, in particular, contain trans-vaccenic acid, which is a molecule with documented anti-cancer properties [Fan et al. 2023].