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    Topic review

    Alpha-Linolenic and Linoleic Fatty Acids

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    Submitted by: Bonny Burns-Whitmore

    Definition

    Good sources of the long-chain n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) include cold-water fish and seafood; however, vegan diets (VGNs) do not include animal-origin foods. 

    1. Introduction

    The polyunsaturated n-6 and n-3 fatty acids are essential for a variety of functions in the body, including the synthesis of prostaglandins, leukotrienes, cellular membranes, phospholipids, retinal photoreceptors (vision), cerebral gray matter (brain tissue), testes, and sperm. Linoleic (18:2n-6; LA) and arachidonic acids (20:4n-6; AA) are classified as n-6 fatty acids, and α-linolenic (18:3n-3; ALA), eicosapentaenoic (20:5n-3; EPA) and docosahexaenoic acids (22:6n-3; DHA) are n-3 fatty acids [1]. Of these fatty acids, LA and ALA are considered essential and must be provided by the diet.
    The Dietary Reference Intakes (DRIs) are “nutrient reference values” developed by the Institute of Medicine of The National Academies. They are intended to serve as a guide for good nutrition and provide the scientific basis for the development of food guidelines in both the United States and Canada, and these nutrient reference values are specified on the basis of age, gender and lifestage groups” [2]. The United States DRIs are used to make informed judgements during the dietary planning process. New research or discoveries of physiological factors, inborn errors of metabolism, health risks, characteristics of the nutrient sources, and nutrient bioavailability may require adjustments in DRI nutrient values for planning individual and group dietary intakes. The present 2003 version of the DRIs states that the nutrients of concern for vegetarians and vegans (VGNs) are vitamin B12, vitamin D, calcium, iron, zinc, and protein [3]. Essential fatty acids in the VGN and vegetarian diets are not presently a DRI concern.
    When the DRI concludes that there is inadequate information to set either LA or ALA Estimated Average Requirements (EAR) or the Recommended Dietary Allowance (RDA) for healthy individuals, the Adequate Intake (AI) is used. The present essential fatty acid AI is based on “the highest median intake of LA and ALA in United States adults, where a deficiency is basically nonexistent in non-institutionalized populations” [4]. The present n-6 AI requirement range is 12–11 g/day for men and 17–14 g/day for adult women (non-pregnant/lactating), and the AI n-3 fatty acid recommendations are 1.1 g/day of ALA for women and 1.6 g/day for men [4]. However, it is unknown if the AIs are beneficial or physiologically adequate because dose-response data studies are lacking, Essential fatty acid status is not usually clinically tested, and absence of deficiency symptoms is not necessarily evidence of adequacy.
    The authors utilized the definition of ‘vegan’ as the following: a diet which is “devoid of all flesh foods. It excludes eggs and dairy products and may exclude honey” [5]. Frequently, the term ‘strict vegetarian’ or ‘total vegetarian’ is used instead of ‘vegan’ to describe their dietary pattern. Thus, the abbreviation ‘VGN’ is used in this manuscript as a description of the dietary pattern of total vegetarians/strict vegetarians and vegans.
    People choose VGN or vegetarian diets for different reasons, which include but are not limited to health reasons, compassion toward animals, a desire to better protect the environment, to lower their risk of chronic diseases, or to therapeutically manage diseases; however, these diets require careful dietary planning. According to the Position Paper of the Academy of Nutrition and Dietetics regarding vegetarian diets, “Well designed vegetarian diets provide adequate nutrient intakes for all stages of the lifecycle and can also be useful in the management of some chronic diseases” [5].
    Upon examination of the published articles that relate to ‘vegetarian’, the researcher’s definitions for the terms ‘vegan’ and ‘vegetarian’ are inconsistent, and some researchers consider plant-based diets to be ‘semi-vegetarian’. However, VGN diets are very different from omnivore diets and even diets that are considered to be ‘vegetarian’ (ex. ‘lacto-ovo’, ‘pesco-vegetarian’, ‘plant-based vegetarian’, ‘pollo-vegetarian’, or ‘semi-vegetarian’). These ‘vegetarian’ diets may also include animal-origin foods such as eggs, dairy, fish, or chicken. Thus, dietary patterns and levels of biochemical indicators of essential fatty acid status are very different between VGN and omnivore diets or even other types of vegetarian diets. This narrative review focuses on apparently healthy VGNs and comparisons of VGNs and ‘omnivore’ or ‘meat-eating’ diets, rather than the comparisons of VGN to vegetarian diets or other terms that include the word ‘vegetarian’.
    Diet study results between VGNs and omnivores/meat-eaters are inconsistent. Additionally, interpretation or comparison is difficult when some of the information is not reported, or missing. For example, some studies report dietary total polyunsaturated fatty acids (PUFAs), total n-6, total n-3, or collected some, but not all lipid fractions [6][7][8][9][10][11], which limits interpretation of essential fatty acid biological indicators as compared to dietary intakes.
    Additional fatty acids of interest are EPA and DHA. They are not considered to be essential since they can be converted from ALA; however, they may be of concern for VGNs, since VGN diets are typically absent of EPA and DHA unless VGNs consume supplements containing EPA and DHA [9][12][13][14][15][16].

    2. Dietary Sources of the Essential Fatty Acids

    The most plentiful dietary n-6 polyunsaturated fatty acid is LA. N-6 fatty acid food sources commonly consumed by VGNs include nuts, seeds, certain vegetables, and vegetables oils such as soybean oil, safflower oil, and corn oil. Therefore, any diet that is mostly plant-based leads to a high dietary intake of LA as well as fiber. Since there are few plant sources high in ALA compared to LA, this may present an intake challenge for VGNs to meet the ALA DRI requirements.
    The most abundant n-3 PUFA is ALA, which is found in plant-based oils and/or oil food sources like flaxseed (linseed), English walnut, hemp seed, and chia [17]. The major dietary plant-based sources of LA and ALA are shown in Table 1.
    Table 1. Energy, protein, total lipid, 18:2 n-6, 18:3 n-3, carbohydrate, and fiber contents of oils and foods commonly consumed by vegans and vegetarians for the essential fatty acids.

    Nutrient 1

     

    Energy

    Protein

    Total Lipid

    18:2n-6

    18:3n-3

    CHO

    Total Fiber

     

    Unit

    Kcal

    g

    g

    g

    g

    g

    g

    Oils

                   

    Oil, Canola

    100 g

    884

    0

    100

    18.64

    9.137

    0

    0

    Oil, Flaxseed/Linseed (Panos)

    100 g

    884

    0.110

    99.98

    14.25

    53.37

    0

    0

    Oil, Soybean

    100 g

    763

    0

    100

    50.42

    6.789

    0

    0

    Oil, Walnut

    100 g

    884

    0

    100

    52.90

    10.40

    0

    0

    Oil, High Oleic Sunflower

    100 g

    884

    0

    100

    3.61 *

    0.192 **

    0

    0

    Oil, High Oleic Safflower

    100 g

    884

    0

    100

    12.72

    0.096

    0

    0

    Oil, Culinary Algae

    100 g

    800

    0

    93.33

    n/a

    n/a

    0

    0

    Ovega-3 supplement 2

    1 gel

    n/a

    0

    n/a

    n/a

    0.5

    0

    0

    Deva Vegan supplement 3

    1 cap

    5

    0

    0.5

    n/a

    0.2

    0

    0

    Nordic Naturals supplement 4

    2 gels

    10.0

    0

    1.00

    n/a

    0.715

    0

    0

    Food Sources

                   

    Almonds Raw

    100 g

    579

    21.15

    49.93

    12.30

    0.003

    21.55

    12.50

    Amaranth

    100 g

    371

    13.65

    7.020

    2.736

    0.042

    65.25

    6.70

    Avocados, Raw, California

    100 g

    167

    1.960

    15.41

    1.674

    0.111

    8.640

    6.80

    Black Walnuts Dried

    100 g

    619

    24.06

    59.33

    33.80

    2.680

    9.580

    6.80

    Brazil Nuts, Dried

    100 g

    659

    14.32

    67.10

    23.859

    0.018

    11.74

    7.50

    Brown Rice Cooked

    100 g

    123

    2.740

    0.970

    0.355

    0.011

    25.58

    1.60

    Bulgur Cooked

    100 g

    83

    3.08

    0.240

    0.094

    0.004

    18.58

    4.50

    Cashews Raw

    100 g

    553

    18.22

    43.85

    7.782

    0.062

    30.19

    3.30

    Chia Seeds Dried

    100 g

    486

    16.54

    30.74

    5.840

    17.80

    42.12

    34.4

    English Walnuts Dried

    100 g

    654

    15.23

    65.21

    38.09

    9.08

    13.71

    6.70

    Flaxseed Raw

    100 g

    534

    18.29

    42.16

    5.903

    22.81

    28.88

    27.3

    Hempseed Hulled

    100 g

    553

    31.56

    48.75

    1.340

    8.864

    8.670

    4.00

    Millet Cooked

    100 g

    119

    3.510

    1.000

    0.480

    0.028

    23.67

    1.300

    Oat Bran Cooked

    100 g

    40

    3.210

    0.860

    0.324

    0.015

    11.44

    2.60

    Pistachio Raw

    100 g

    560

    20.16

    45.32

    13.10

    0.210

    27.17

    10.60

    Poppy Seeds

    100 g

    525

    17.99

    41.56

    28.30

    0.273

    28.13

    19.50

    Quinoa

    100 g

    368

    14.12

    6.070

    2.977

    0.260

    64.16

    7.00

    Rye

    100 g

    338

    10.34

    1.630

    0.659

    0.108

    75.86

    15.1

    Sesame Seeds dried

    100 g

    573

    17.73

    49.67

    21.375

    0.376

    23.45

    11.8

    Soybeans Raw

    100 g

    446

    36.49

    19.94

    9.925

    1.330

    30.16

    9.30

    Soybeans, Boiled

    100 g

    141

    12.35

    6.400

    2.657

    0.354

    11.05

    4.20

    Sunflower Seeds

    100 g

    584

    20.78

    51.50

    23.05 *

    0.06 **

    20.00

    8.60

    1 Source: US Department of Agriculture Nutrient Data Base, 2019 [17]. * undifferentiated 18:2, ** undifferentiated 18:3. 2 Ovega-3 i-Health, Inc., 2017 [18]. 3 Deva Nutrition LLC, 2017 [19]. 4 Nordic Naturals Inc., 2017 [20].
    Good sources of EPA and DHA fatty acids are typically found in animals, eggs from laying chickens fed high sources of ALA or DHA, fish or livestock fed n-3 supplements, cold water fish and seafood, or fish which feed on food sources high in ALA, EPA and/or DHA. Some cold water marine algae (except spirulina) contain long chain n-3 fatty acids, and negligible amounts of ALA and LA (Table 1).
    Many of the food sources high in LA also contain ALA (Table 1). Thus, it is very difficult to obtain ALA without also increasing the amount of LA in the diet, unless specific foods high in ALA are consumed such as flaxseed, flaxseed/linseed oil, hemp seeds, chia or oils high in high oleate sunflower oil and low in LA (Table 1). Decreasing LA intake in VGNs could be an option; however, decreasing LA intake without monitoring and/or increasing ALA intake might also affect EPA and DHA conversion.
    Additionally, there are concerns and considerations such as nutrient bioavailability, physiological implications, and possible health risks of high LA and low ALA in the diet, as well as high LA in plasma, serum, erythrocytes, platelets, breastmilk and adipose tissue.

    3. Nutrient Bioavailability

    It is possible that high fiber diets interfere with fat absorption, including essential fatty acids. Since VGNs typically consume plant products, their diets are typically high in total fiber [6][7][8][14][21]. Soluble fibers such as psyllium, gums and beta-glucan [17], bind fatty acids and prevents them from being absorbed and binds bile, which is necessary for micelle formation. Micelles are required for uptake of long-chain fatty acids into the enterocytes. Insoluble fiber, such as wheat bran, fruit skins, and whole grains [17] increase transit time through the intestine and can also interfere with uptake of fats as well as nutrients in general, because both types of fiber are not digested or absorbed in the small intestine, and humans do not have enzymes to digest fiber. Presently, there are no studies on the effects of high soluble or insoluble fiber on fat digestion in VGNs.

    4. Physiological Reasons for Special Consideration-Conversion of ALA to EPA and DHA

    The essential PUFAs, LA and ALA, must be consumed from the diet, and since VGNs do not consume EPA and DHA from the diet, VGNs rely on endogenous synthesis to obtain long chain n-3 PUFAs. ALA is endogenously converted to EPA and DHA by the elongation and desaturation enzymes in the animal (or marine algae) and becomes incorporated into the animal’s cells and/or stored in adipose tissue. Thus, almost all EPA and DHA dietary sources come from animals and VGNs are limited to algal supplements of EPA and DHA.
    Most humans (except those with inborn errors of metabolism) can convert LA to AA and modestly convert ALA to EPA and/or DHA. The human conversion rate of ALA to EPA and DHA is about 5%–8% [22][23][24]. This low conversion rate suggests humans should consume dietary sources of EPA and DHA; however, evidence is not conclusive regarding the amount needed to maintain physiological function.
    Both LA and ALA are metabolized by the same biochemical pathway, and excess consumption of LA or ALA results in competition between the elongation and desaturation enzymes for EPA and AA. Excess LA competitively interferes with the ability of ALA to utilize the elongation and desaturase enzymes, thereby suppressing the conversion of ALA to EPA and EPA to DHA [22][23][24][25][26][27] (Figure 1).
    Figure 1. The elongation and desaturation of the essential fatty acids, linoleic acid (LA) and alpha-linolenic acid (ALA). AA: arachidonic acid; EPA: eicosapentaenoic acid; DHA: docosahexaenoic acid; PUFA: polyunsaturated fatty acids. Permission by authors and Elsevier [28].
    Adult and infant studies have demonstrated the conversion of ALA to EPA and DHA through desaturation and elongation, and LA desaturates and elongates to form AA. Through the process of elongation, desaturation and beta oxidation 22:5n-6 forms from AA, using the same enzyme system needed for conversion of EPA to DHA [19][20][21][22][23][24][25][26][27]. In supplemented omnivores and vegetarians, 9.4% of serum phospholipid DHA can be retro-converted to EPA [12].
    It may be possible to observe alterations in the synthesis of EPA and DHA from ALA by following a VGN diet over the long-term, as it has been demonstrated that changes in dietary patterns may affect the synthesis of n-3 fatty acids. For example, there is an increased synthesis of DHA from ALA, especially if LA is decreased [29]; ALA is elongated and desaturated in a tissue-dependent manner [30]; and n-3 PUFAs may be depleted during overnutrition [31].

    5. Recommended Intakes of n-3 and the n-6:n-3 Ratio

    Expert opinions differ when it comes to n-3 and n-6:n-3 ratio recommendations (Table 2—most recent studies are listed first) and overall, the recommendations for dietary n-6:n-3 suggested by experts and researchers are lower than 10:1 and between the range of 2–4:1 [32][33][34][35].
    Table 2. Recommendations by researchers and reviewers for adult vegans/total vegetarians (VGNs) (most recent studies first).

    Author, Year

    Recommendation:

    Males; Females

    Combined

    18:2n-6 LA

    18:3 n-3 ALA

    20:5 n-3 EPA

    22:6 n-3 DHA

    n-6:n-3 or Omega-3 Index

    Agnoli et al., 2017 [36]

    Females

    Limit intake of sources of n-6 FA, & TFA. Limit consumption of processed, deep-fried foods, and alcohol.

    -

    Pregnant/breastfeeding or women with increased requirement for long chain n-3 fatty acids, should be advised to consume an algae-based supplement of known nutrient content.

    Pregnant/breastfeeding or women with increased requirement for long chain n-3 fatty acids, should be advised to consume an algae-based supplement of known nutrient content.

    -

    Combined-Males and Females

    -

    Improve n-3 nutritional status by regular consumption of good sources of alpha-linolenic acid.

    -

    -

    -

    Burdge et al., 2017 [37]

    Females

    -

    -

    -

    Need more cognitive studies for children of vegetarian females due to low DHA levels.

    -

    Pinto et al., 2017 [9]

    Combined

    -

    Further research whether populations with low n-3 status are more at risk of having a pro-inflammatory profile.

    -

    -

    -

    Melina et al., 2016 [5]

    Females

    -

    -

    -

    Low dose microalgae DHA supplements for pregnancy and lactation.

    -

    Combined

    High intakes of LA may suppress ALA conversion.

    May be prudent to ensure higher intakes of ALA. N-3 needs of healthy individuals can be met with ALA alone; endogenous synthesis of EPA and DHA from ALA is sufficient.

    Clinical relevance of reduced EPA and DHA status in VGNs are unknown. Low-dose micro-algae based DHA supplements are available for those with increased needs.

    Clinical relevance of reduced EPA and DHA status in VGNs are unknown. Low-dose micro-algae based DHA supplements are available for those with increased needs.

    A ratio of LA/ALA not exceeding 4:1 has been suggested for optimal conversion.

    Harris, 2014 [38]

    Combined

    Consume more ALA and less LA to increase the Omega-3 Index.

    Consume more ALA and less LA to increase the Omega-3 Index.

    -

    -

    Omega-3 Index >8%.

    Sarter et al., 2014 [16]

    Combined

    -

    -

    VGNs respond

    robustly to a relatively low dose of a vegetarian omega-3 supplement.

    VGNs respond

    robustly to a relatively low dose of a vegetarian omega-3 supplement.

    No direct evidence that omega-3 index confers additional health benefits over and above their already protective VGN diet.

    Saunders et al., 2013 [15]

    Combined

    -

    Double current AI of ALA if no direct sources of EPA and DHA are consumed. Increased needs or reduced conversion may benefit from DHA and EPA supplements derived from microalgae of 200–300 mg/day of DHA and EPA (pregnant and lactating women) and reduced conversion ability.

    -

    -

    -

    Craig, 2010; Review [39]

    Combined

    -

    Regular consumption of plant foods naturally rich in n-3 fatty acid ALA, such as ground flaxseed, walnuts, soy products, and hemp seed beverages.

    -

    Pregnant and lactating women may benefit from DHA-fortified foods and microalgae-derived DHA supplements.

    -

    Welch et al., 2010 [40]

    Combined

    -

    Further research for conversion of ALA to long chain n-3 PUFAs for maintenance of adequate status in non-fish and fish-oil consumers is required.

    -

    -

    -

    Simopoulos, 2008 [41]

    Combined

    -

    -

    -

    -

    Ratio of 4:1 is associated with 70% decrease in total mortality in secondary prevention of cardiovascular disease.

    Kornsteiner et al., 2008 [32]

    Combined

    -

    Erythrocyte phospholipid n-3 status of VGNs is critical. It is important to maintain n-3 fatty acid intake during adult life.

    -

    -

    Ensure physical, mental and neurological health, reduce n-6/n-3 ratio with an additional intake of direct sources of EPA and DHA, regardless of age and gender.

    Mann et al., 2006 and Li et al., 1999 (Mann used data collected from Li, 1999) [42]

    Combined

    -

    Advised to increase intake of n-3 fatty acids to increase platelet PL n-3 PUFA and reduce platelet aggregability.

    -

    -

    -

    Rosell et al., 2005 [10]

    Combined

    -

    Suggests (with caution) VGNs increase intake of ALA and limit intake of LA to optimize FA status. The importance of long chain fatty acids in the diet needs further investigation.

    -

    -

    -

    Davis et al., 2003 [34]

    Combined

    5.5–8% Kcals from n-6 FA. Reduce high n-6 oils in the diet, decrease processed foods. Primary fat should be MUFA.

    <1.5–2% of calories should be obtained from n-3. Decrease EtOH and trans fatty acids to increase conversion of ALA to EPA and DHA. Double intake of ALA; provide >1% of energy from n-3 or about 1.1 g/1000 calories. Increased needs require 2.2 g/1000 calories. Aim for 2–4 g of ALA/day.

    Not essential, but it is important to ensure sufficient levels by relying on conversion from parent fatty acids. Two important steps to improve EPA status: 1) Maximize conversion of ALA to EPA and DHA and 2) Provide a direct source of EPA and DHA.

    Not technically essential, but ensure sufficient levels by relying on conversion from parent fatty acids. Supplements of DHA should be 100–300 mg/day. DHA and ALA should also be adequate.

    To achieve the 4:1 ratio, <1.5–2% of calories should be obtained from n-3 and 5.5–8% of calories from n-6 FA.

    Simopoulos, 2000 [35]

    Combined

    -

    -

    -

    -

    Ratio was 1:1 to 2:1 in ancient diets. Present ratio is 10 to 1:20 to 25 to 1- indicates a deficiency in Western Diets of n-3.

    Fokkema et al., 2000 [33]

    Combined

    -

    -

    -

    -

    Found a 3:1 ratio increased EPA from 0.3 to about 1.0% in VGN plasma. A 3.7 g/day ALA diet for 4 weeks (ratio of 3.8:1) augmented ALA about 1% more. Total n-3 levels increased from 2.3 to 3.4% in plasma. DHA status was not increased.

    Agren et al., 1995 [43]

    Combined

    Depressed levels of n-3 FA are depressed due to very low diet levels and high LA and oleic acid intake.

    -

    -

    -

    -

    Sanders et al., 1978 [44]

    Females

    -

    More research is needed on low delta 4 desaturase in lactating women.

    -

    -

    -

    Combined

    -

    Further research needed to establish whether differences in the proportion of n-3 derivatives in tissues are of physiological importance.

    -

    -

    -

    The ratio of n-6 fatty acids to n-3 fatty acids can influence the conversion of ALA to EPA and DHA [45][46]. Gerster found that a diet high in n-6 reduces the ALA to EPA and DHA conversion by 40–50% [45]. When healthy men increased dietary intake of LA from 15 g/day to 30 g/day (increased n-6:n-3 ratio) this resulted in a 40–54% increase in conversion of LA to AA, as well as a subsequent decrease in conversion of ALA to EPA and DHA [46]. Additionally, high n-6:n-3 ratios in obesity are directly related to non-alcoholic fatty liver disease [31].
    Several VGN studies have determined dietary intake and status of the n-6:n-3 ratios. The majority of VGNs have n-6:n-3 plasma ratios that are ‘unbalanced’ [10][13][21][32][43][34]. Kornsteiner et al. reported that a ratio of 10:1 promoted n-3 tissue declines and reduced desaturation and elongation of n-3 fatty acid-related products, and suggested that VGNs achieve a balanced ratio of n-6:n-3 in their diet to enhance the conversion of ALA into EPA and DHA [32]. A reduction in the n-6:n-3 ratio to 2–4:1 was shown to maintain normal metabolism and increase the amount of long chain PUFAs synthesized in the body [21]. Simopoulos affirms a balanced n-6:n-3 ratio is a determinant of health because n-6 and n-3 fatty acids influence gene expression, and advocates that a balanced ratio of LA to ALA of 2:1. She also stated that the n-6:n-3 ratio of 10:1 in the diet indicated Western diets are deficient in n-3 [35]. Davis and Kris-Etherton suggested optimizing status by consuming double the intake of ALA (≥1% of energy or 1.1 g/1000 Kcals and aim for 2–4 g/ALA/day) and a direct source of DHA in the range of 100–300 mg/day [34]. The authors of the Position Paper of the Academy of Nutrition and Dietetics on Vegetarian Diets suggest that the LA/ALA ratio should not exceed 4:1 and that “it may be prudent to ensure a somewhat higher intake of ALA” [5].
    A dietary increase in flaxseed (linseed) oil increases plasma ALA and EPA and lowers the ratio of n-6:n-3 [40][47][48][49]. Li et al. showed dietary ALA from canola and linseed (flaxseed) oil increased the EPA tissue profile 2.5-fold in a high ALA diet compared with a 0.5-fold increase in a moderate ALA diet in male subjects 20 to 50 years old [50]. Indu found that a constant intake of 3.7 g/day of dietary ALA may have biological effects similar to those of 0.3 g/day of dietary long chain n-3 PUFAs from fish oil. Eleven grams of ALA from flaxseed produces 1 g of the long chain n-3 PUFAs, EPA and DHA, and results in a calculated ratio of 14.8 g LA: 3.7 g ALA equivalent to a 4:1 ratio [48]. Supplementation with high amounts of ALA (>5.3 g/day) increased EPA plasma fatty acid and platelet concentrations [49][51]. Bjerve et al. noted that the minimum requirement for ALA in immobile adults was equivalent to 0.2% of total energy intake when n-3 long chain fatty acids were 0.08% of energy [52].

    The entry is from 10.3390/nu11102365

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