ABSTRACT

Recently, vegetarian diets have experienced an increase in popularity. A vegetarian diet is associated with many health benefits because of its higher content of fiber, folic acid, vitamins C and E, potassium, magnesium, and many phytochemicals and a fat content that is more unsaturated. Compared with other vegetarian diets, vegan diets tend to contain less saturated fat and cholesterol and more dietary fiber. Vegans tend to be thinner, have lower serum cholesterol, and lower blood pressure, reducing their risk of heart disease. However, eliminating all animal products from the diet increases the risk of certain nutritional deficiencies. Micronutrients of special concern for the vegan include vitamins B-12 and D, calcium, and long-chain n-3 (omega-3) fatty acids. Unless vegans regularly consume foods that are fortified with these nutrients, appropriate supplements should be consumed. In some cases, iron and zinc status of vegans may also be of concern because of the limited bioavailability of these minerals.

INTRODUCTION

A nationwide poll conducted in April 2006 by Harris Interactive reported that 1.4% of the American population is vegan, in that they eat no meat, fish, dairy, or eggs (1). Vegan diets are growing in popularity today among teenagers and youth, especially females. For many vegans, nutritional choices center around taking better care of the earth’s resources and the environment, ethical issues about animal care, the use of antibiotics and growth stimulants for the production of animals, the threat of animal-borne diseases, and the health advantages of a plant-based diet (26). In addition, the potential of allergies from dairy products and lactose intolerance have fueled the popularity of soy-based dairy substitutes.

What then is the nutritional and health status of those who follow a vegan diet? Compared with other vegetarians (eg, lactoovovegetarians), are there any advantages or disadvantages to following a vegan diet? Does the elimination of dairy and eggs offer any additional benefits or create potential concerns? The purpose of this brief review is to summarize current knowledge on the health effects of vegan diets, to discuss the nutritional concerns or shortfalls of a vegan diet and to provide some practical dietary recommendations for following a healthy vegan diet. Key et al (7) have provided a pertinent overview of the health effects of vegetarian diets, focusing on their European Prospective Investigation into Cancer and Nutrition–Oxford (EPIC-Oxford) study and other large population studies.

HEALTH EFFECTS OF VEGAN DIETS

Vegan diets are usually higher in dietary fiber, magnesium, folic acid, vitamins C and E, iron, and phytochemicals, and they tend to be lower in calories, saturated fat and cholesterol, long-chain n-3 (omega-3) fatty acids, vitamin D, calcium, zinc, and vitamin B-12 (8). In general, vegetarians typically enjoy a lower risk of cardiovascular disease (CVD), obesity, type 2 diabetes, and some cancers (3). A vegan diet appears to be useful for increasing the intake of protective nutrients and phytochemicals and for minimizing the intake of dietary factors implicated in several chronic diseases (9). In a recent report (10), different plant food groups were rated with respect to their metabolic-epidemiologic evidence for influencing chronic disease reduction. According to the evidence criteria of the World Health Organization and Food and Agriculture Organization (WHO/FAO), cancer risk reduction associated with a high intake of fruit and vegetables was assessed as probable or possible, risk of CVD reduction as convincing, whereas lower risk of osteoporosis was assessed as probable (10). The evidence for a risk-reducing effect of consuming whole grains was assessed as possible for colorectal cancer and probable for type 2 diabetes and CVD. The evidence for a risk-reducing effect of consuming nuts was assessed as probable for CVD (10).

Cardiovascular disease

In summarizing the published research, Fraser (11) noted that, compared with other vegetarians, vegans are thinner, have lower total and LDL cholesterol, and modestly lower blood pressure. This is true not only for whites; work by Toohey et al (12) showed that blood lipids and body mass index (BMI; in kg/m2) were significantly lower in African American vegans than in lactoovovegetarians. Similarly, among Latin Americans, vegetarians had lower plasma lipids than did their omnivore counterparts, with the lowest reported among vegans (13). In that study, plasma total and LDL cholesterol were 32% and 44% lower among vegans than among omnivores. Because obesity is a significant risk factor for CVD, the substantially lower mean BMI observed in vegans may be an important protective factor for lowering blood lipids and reducing the risk of heart disease (8).

Vegans, compared with omnivores, consume substantially greater quantities of fruit and vegetables (1416). A higher consumption of fruit and vegetables, which are rich in fiber, folic acid, antioxidants, and phytochemicals, is associated with lower blood cholesterol concentrations (17), a lower incidence of stroke, and a lower risk of mortality from stroke and ischemic heart disease (18, 19). Vegans also have a higher consumption of whole grains, soy, and nuts (14, 15, 20), all of which provide significant cardioprotective effects (21, 22).

Cancer

Data from the Adventist Health Study showed that nonvegetarians had a substantially increased risk of both colorectal and prostate cancer than did vegetarians (23). A vegetarian diet provides a variety of cancer-protective dietary factors (24). In addition, obesity is a significant factor, increasing the risk of cancer at a number of sites (25). Because the mean BMI of vegans is considerably lower than that of nonvegetarians (8), it may be an important protective factor for lowering cancer risk.

Vegans consume considerably more legumes, total fruit and vegetables, tomatoes, allium vegetables, fiber, and vitamin C than do omnivores (1416, 20, 23). All those foods and nutrients are protective against cancer (25). Fruit and vegetables are described as protective against cancer of the lung, mouth, esophagus, and stomach and to a lesser degree some other sites, whereas the regular use of legumes provides a measure of protection against stomach and prostate cancer. In addition, fiber, vitamin C, carotenoids, flavonoids, and other phytochemicals in the diet are shown to exhibit protection against various cancers, whereas allium vegetables provide protection against stomach cancer, and garlic against colorectal cancer. Foods rich in lycopene, such as tomatoes, are known to protect against prostate cancer (25).

Fruit and vegetables are known to contain a complex mixture of phytochemicals that possess potent antioxidant and antiproliferative activity and show additive and synergistic effects (24, 26). The phytochemicals interfere with several cellular processes involved in the progression of cancer. These mechanisms include inhibiting cell proliferation, inhibition of DNA adduct formation, inhibiting phase 1 enzymes, inhibiting signal transduction pathways and oncogene expression, inducing cell-cycle arrest and apoptosis, inducing phase 2 enzymes, blocking the activation of nuclear factor-κB, and inhibiting angiogenesis (24).

With this wide array of useful phytochemicals in the vegetarian diet, it is surprising that population studies have not shown more pronounced differences in cancer incidence or mortality rates between vegetarians and nonvegetarians (7, 27). The bioavailability of the phytochemicals, which depends among other things on food preparation methods, may be an important determining factor. However, new evidence suggests that a low vitamin D status, a problem often reported in vegan populations (8, 28), is associated with an increased risk of cancers (29, 30).

The sources of protein avoided or consumed by vegans also have definite health consequences. Red meat and processed meat consumption are consistently associated with an increase risk of colorectal cancer (25). Those in the highest quintile of red meat intake had elevated risks, ranging from 20% to 60%, of esophageal, liver, colorectal, and lung cancers than did those in the lowest quintile of red meat intake (31). In addition, the use of eggs was recently shown to be associated with a higher risk of pancreatic cancer (32). Although vegans avoid consuming red meat and eggs altogether, they consume greater amounts of legumes than do omnivores (14, 16, 20). This protein source was seen in the Adventist Health Study to be negatively associated with risk of colon cancer (23). New data suggest that legume intake is also associated with a moderate reduction in the risk of prostate cancer (33). In Western society, vegans also consume substantially more tofu and other soy products than do omnivores (14, 16). Consumption of isoflavone-containing soy products during childhood and adolescence protects women against the risk of breast cancer later in life (34), whereas a high childhood dairy intake has been associated with an elevated risk of colorectal cancer in adulthood (35). Cancer risk in vegans may be altered because vegans consume soy beverages rather than dairy beverages. Data from the Adventist Health Study showed that consumption of soy milk by vegetarians protected them against prostate cancer (36), whereas in other studies the use of dairy was associated with an increased risk of prostate cancer (25, 3739).

Further research is needed to explore the relation between consuming plant-based diets and risk of cancer because there are many unanswered questions about how diet and cancer are connected. To date, epidemiologic studies have not provided convincing evidence that a vegan diet provides significant protection against cancer. Although plant foods contain many chemopreventive factors, most of the research data comes from cellular biochemical studies.

Bone health

Cross-sectional and longitudinal population-based studies published within the past 2 decades suggest no differences in bone mineral density (BMD), for both trabecular and cortical bone, between omnivores and lactoovovegetarians (40). More recent studies with postmenopausal Asian women showed spine or hip BMD was significantly lower in long-term vegans (41, 42). Those Asian women, who were vegetarian for religious reasons, had low intakes of protein and calcium. An inadequate protein and low calcium intake has been shown to be associated with bone loss and fractures at the hip and spine in the elderly (43, 44). Adequate calcium intake may be a problem for vegans. Although lactoovovegetarians generally consume adequate amounts of calcium, vegans typically fall short of the recommended daily intake for calcium (8, 45, 46). Results from the EPIC-Oxford study provide good evidence that the risk of bone fractures for vegetarians was similar to that of omnivores (46). The higher risk of bone fracture seen in vegans appears to be a consequence of a lower mean calcium intake. No difference was observed between the fracture rates of the vegans who consumed >525 mg calcium/d and the omnivore fracture rates (46).

Bone health depends on more than just protein and calcium intakes. Research has shown that bone health is also influenced by nutrients such as vitamin D, vitamin K, potassium, and magnesium and by foods such as soy and fruit and vegetables (4750). Vegan diets do well in providing a number of those important substances. The maintenance of acid-base balance is critical for bone health. A drop in extracellular pH stimulates bone resorption (51), because bone calcium is used to buffer the pH drop. An acid-forming diet, therefore, increases urinary calcium excretion (52). However, a diet rich in fruit and vegetables that is typical of a vegan diet has a positive effect on the calcium economy and markers of bone metabolism in men and women (49). The high potassium and magnesium content of fruit and vegetables provides an alkaline ash, which inhibits bone resorption (53). Higher intakes of potassium are associated with greater BMD of the femoral neck and lumbar spine of premenopausal women (54).

Blood concentrations of undercarboxylated osteocalcin, a sensitive marker of vitamin K status, is considered an indicator of hip fracture (55) and a predictor of BMD (56). Results from 2 large, prospective cohort studies support an association between vitamin K intake and relative risk of hip fracture. In the Nurses’ Health Study, middle-aged women consuming the most vitamin K had the lowest risk of hip fracture. Risk of hip fracture was decreased 45% for ≥1 servings/d of green leafy vegetables (the main vitamin K source) compared with ≤1 serving/wk (57). In the Framingham Heart Study, elderly men and women in the highest quartile of vitamin K intake had a 65% decreased risk of hip fracture than did those in the lowest quartile (58).

In addition to a high intake of fruit and vegetables, vegans also tend to have a high intake of tofu and other soy products (14, 16). Soy isoflavones are suggested to have a beneficial effect on bone health in postmenopausal women (50). In a meta-analysis of 10 randomized controlled trials, soy isoflavones showed a significant benefit to spine BMD of menopausal women (59). In another meta-analysis, soy isoflavones significantly inhibited bone resorption and stimulated bone formation compared with placebo (60). In a randomized clinical trial lasting 24 mo involving osteopenic postmenopausal women, increases in BMD of both lumbar spine and femoral neck were substantially greater with the soy isoflavone, genistein, than with placebo (61).

As long as the calcium and vitamin D intake of vegans is adequate, their bone health is probably not an issue because their diet contains an ample supply of other protective factors for bone health. However, more studies are needed to provide more definitive data on the bone health of vegans.

POTENTIAL NUTRITIONAL SHORTFALLS

To obtain a nutritionally adequate diet, the consumer must first have an appropriate knowledge of what constitutes a nutritionally adequate diet. Second, accessibility is important, ie, the availability of certain foodstuffs and foods fortified with key nutrients that are otherwise lacking in the diet. This accessibility will vary greatly, depending on the geographic region of the world, because different countries have different fortification laws. The following section deals with nutrients of concern in the vegan diet. The problem of insufficient calcium has already been discussed in the section on bone health.

n-3 Polyunsaturated fat

Diets that do not include fish, eggs, or sea vegetables (seaweeds) generally lack the long-chain n-3 fatty acids, eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), which are important for cardiovascular health as well as eye and brain functions. The plant-based n-3 fatty acid α-linolenic acid (ALA; 18:3n-3) can be converted into EPA and DHA, albeit with a fairly low efficiency (62, 63). Compared with nonvegetarians, vegetarians, and especially vegans, tend to have lower blood concentrations of EPA and DHA (64). However, vegans can obtain DHA from microalgae supplements containing DHA, as well as from foods fortified with DHA. However, EPA can be obtained from the retroconversion of DHA in the body. The oil from brown algae (kelp) has also been identified as a good source of EPA.

The new Dietary Reference Intakes recommend intakes of 1.6 and 1.1 g ALA/d for men and women, respectively, which accounts for <1% of the daily calories. Presently, the intake of EPA plus DHA in the United States is only 0.1–0.2 g/d, with the DHA intake being ≈2–3 times the intake of EPA (65). Vegans should be able to easily reach the n-3 fatty acid requirements by including regular supplies of ALA-rich foods in their diet and also DHA-fortified foods and supplements. However, DHA supplements should be taken with caution. Although they can lower plasma triacylglycerol, they can raise total and LDL cholesterol (66, 67), cause excessively prolonged bleeding times, and impair immune responses (65).

Vitamin D

In the EPIC-Oxford study, vegans had the lowest mean intake of vitamin D (0.88 μg/d), a value one-fourth the mean intake of omnivores (8). For a vegan, vitamin D status depends on both sun exposure and the intake of vitamin D-fortified foods. Those living in areas of the world without fortified foods would need to consume a vitamin D supplement. Living at high latitudes can also affect one’s vitamin D status, because sun exposure in that region is inadequate for several months of the year (68). Those who are dark skinned, elderly, who extensively cover their body with clothing for cultural reasons, and who commonly use sunscreen are at an increased risk of vitamin D deficiency (45). Another matter of concern for vegans is that vitamin D2, the form of vitamin D acceptable to vegans, is substantially less bioavailable than the animal-derived vitamin D3 (69).

In Finland, the dietary intake of vitamin D in vegans was insufficient to maintain serum 25-hydroxyvitamin D and parathyroid hormone concentrations within normal ranges in the winter, which appeared to have a negative effect on long-term BMD (28). Throughout the year serum 25-hydroxyvitamin D concentrations were lower and parathyroid hormone higher in vegan women than in omnivores and other vegetarians. BMD in the lumbar region of the spine was 12% lower in vegans than in omnivores.

Iron

Heme iron absorption is substantially higher than non-heme iron from plant foods. However, hemoglobin concentrations and the risk of iron deficiency anemia are similar for vegans compared with omnivores and other vegetarians (70). Vegans often consume large amounts of vitamin C–rich foods that markedly improve the absorption of the nonheme iron. Serum ferritin concentrations are lower in some vegans, whereas the mean values tend to be similar to the mean values of other vegetarians but lower than the mean value for omnivores (71). The physiologic significance of low serum ferritin concentrations is uncertain at this time.

Vitamin B-12

Compared with lactoovovegetarians and omnivores, vegans typically have lower plasma vitamin B-12 concentrations, higher prevalence of vitamin B-12 deficiency, and higher concentrations of plasma homocysteine (72). Elevated homocysteine has been considered a risk factor for CVD (73) and osteoporotic bone fractures (74). Vitamin B-12 deficiency can produce abnormal neurologic and psychiatric symptoms that include ataxia, psychoses, paresthesia, disorientation, dementia, mood and motor disturbances, and difficulty with concentration (75). In addition, children may experience apathy and failure to thrive, and macrocytic anemia is a common feature at all ages.

Zinc

Vegetarians are often considered to be at risk for zinc deficiency. Phytates, a common component of grains, seeds, and legumes, binds zinc and thereby decreases its bioavailability. However, a sensitive marker to measure zinc status in humans has not been well established, and the effects of marginal zinc intakes are poorly understood (76). Although vegans have lower zinc intake than omnivores, they do not differ from the nonvegetarians in functional immunocompetence as assessed by natural killer cell cytotoxic activity (14). It appears that there may be facilitators of zinc absorption and compensatory mechanisms to help vegetarians adapt to a lower intake of zinc (77).

DIETARY RECOMMENDATIONS FOR OPTIMAL VEGAN DIETS

  1. 1) To avoid B-12 deficiency, vegans should regularly consume vitamin B-12–fortified foods, such as fortified soy and rice beverages, certain breakfast cereals and meat analogs, and B-12–fortified nutritional yeast, or take a daily vitamin B-12 supplement. Fermented soy products, leafy vegetables, and seaweed cannot be considered a reliable source of active vitamin B-12. No unfortified plant food contains any significant amount of active vitamin B-12.

  2. 2) To ensure adequate calcium in the diet, calcium-fortified plant foods should be regularly consumed in addition to consuming the traditional calcium sources for a vegan (green leafy vegetables, tofu, tahini). The calcium-fortified foods include ready-to-eat cereals, calcium-fortified soy and rice beverages, calcium-fortified orange and apple juices, and other beverages. The bioavailability of the calcium carbonate in the soy beverages and the calcium citrate malate in apple or orange juice is similar to that of the calcium in milk (78, 79). Tricalcium phosphate–fortified soy milk was shown to have a slightly lower calcium bioavailability than the calcium in cow milk (78).

  3. 3) To ensure an adequate vitamin D status, especially during the winter, vegans must regularly consume vitamin D–fortified foods such as soy milk, rice milk, orange juice, breakfast cereals, and margarines that are fortified with vitamin D. Where fortified foods are unavailable, a daily supplement of 5–10 μg vitamin D would be necessary. The supplement would be highly desirable for elderly vegans.

  4. 4) A vegan should regularly consume plant foods naturally rich in the n-3 fatty acid ALA, such as ground flaxseed, walnuts, canola oil, soy products, and hemp seed–based beverages. In addition, it is recommended that vegans consume foods that are fortified with the long-chain n-3 fatty acid DHA, such as some soy milks and cereal bars. Those with increased requirements of long-chain n-3 fatty acids, such as pregnant and lactating women, would benefit from using DHA-rich microalgae supplements.

  5. 5) Because of the high phytate content of a typical vegan diet, it is important that a vegan consume foods that are rich in zinc, such as whole grains, legumes, and soy products, to provide a sufficient zinc intake. Benefit could also be obtained by vegans consuming fortified ready-to-eat cereals and other zinc-fortified foods.

A more comprehensive list of eating guidelines for vegans is available elsewhere (80).

FURTHER RESEARCH NEEDED

The term vegetarian is often used to describe a whole range of diets practiced with varying degrees of restriction, making it a challenge to meaningfully compare and contrast the health benefits of various vegetarian diets. Although preliminary data are valuable, more scientific studies on vegans are needed to get a clearer picture of their health status (7, 11). Current data show that vegans have a lower risk of heart disease than do omnivores and other vegetarians, but there are too few studies on other risk factors for definitive conclusions. One small pilot trial has shown that a vegan diet improves glycemic control in individuals with type 2 diabetes (81), but more studies are needed that look at the effects of a vegan diet on the risk of diabetes, as well as cancer. On the basis of our present knowledge, vegans do not appear likely to have any significant advantages over other vegetarians about chronic disease patterns (11). The vegan studies that do exist often involve only a small number of subjects. More studies are also needed with long-term vegans because the health advantages appear more clearly defined when a person has been following a plant-based diet for >5 y (82). Research is also needed to investigate whether the age at which a vegan diet is adopted has any influence on health outcomes.

SUMMARY

Vegans are thinner, have lower serum cholesterol and blood pressure, and enjoy a lower risk of CVD. BMD and the risk of bone fracture may be a concern when there is an inadequate intake of calcium and vitamin D. Where available, calcium- and vitamin D–fortified foods should be regularly consumed. There is a need for more studies on the relation between vegan diets and risk of cancer, diabetes, and osteoporosis. Vitamin B-12 deficiency is a potential problem for vegans, so that the use of vitamin B-12–fortified foods or supplements are essential. To optimize the n-3 fatty acid status of vegans, foods rich in ALA, DHA-fortified foods, or DHA supplements should be regularly consumed. Vegans generally have an adequate iron intake and do not experience anemia more frequently than others. Typically, vegans can avoid nutritional problems if appropriate food choices are made. Their health status appears to be at least as good as other vegetarians, such as lactoovovegetarians. (Other articles in this supplement to the Journal include references 83109.)

The author had no financial disclosures to report.

FOOTNOTES

2

Presented at the symposium, “Fifth International Congress on Vegetarian Nutrition,” held in Loma Linda, CA, March 4–6, 2008.

REFERENCES

1.

Stahler
C
.
How many adults are vegetarian?
Veg J
2006
;
25
:
14
5
.

2.

Jacobsen
MF
.
Six arguments for a greener diet: how a more plant-based diet could save your health and the environment
.
Washington, DC
:
Center for Science in the Public Interest
,
2006
.

3.

Position of the American Dietetic Association and Dietitians of Canada
.
Vegetarian diets
.
J Am Diet Assoc
2003
;
103
:
748
65
.

4.

Fox
N
,
Ward
K
.
Health, ethics and environment: a qualitative study of vegetarian motivations
.
Appetite
2008
;
50
:
422
9
.

5.

Rollin
BE
.
Farm animal welfare: social, bioethical, and research issues
.
Ames, IA
:
Wiley-Blackwell
,
2003
.

6.

Volpe
T
.
The fast food craze: wreaking havoc on our bodies and our animals
.
Parks, AZ
:
Volpe T Canyon Publishing
,
2005
.

7.

Key
TJ
,
Appleby
PN
,
Rosell
MS
.
Health effects of vegetarian and vegan diets
.
Proc Nutr Soc
2006
;
65
:
35
41
.

8.

Davey
GK
,
Spencer
EA
,
Appleby
PN
,
Allen
NE
,
Knox
KH
,
Key
TJ
.
EPIC-Oxford: lifestyle characteristics and nutrient intakes in a cohort of 33,883 meat-eaters and 31,546 non meat-eaters in the UK
.
Public Health Nutr
2003
;
6
:
259
69
.

9.

Dewell
A
,
Weidner
G
,
Sumner
MD
,
Chi
CS
,
Ornish
D
.
A very-low fat vegan diet increases intake of protective dietary factors and decreases intake of pathogenic dietary factors
.
J Am Diet Assoc
2008
;
108
:
347
56
.

10.

Strohle
A
,
Waldmann
A
,
Wolters
M
,
Hahn
A
.
Vegetarian nutrition: preventive potential and possible risks. Part 1: plant foods
.
Wien Klin Wochenschr
2006
;
118
:
580
93
.

11.

Fraser
G
.
Risk factors and disease among vegans
. In:
Fraser
G
ed.
Diet, life expectancy, and chronic disease. Studies of Seventh-day Adventists and other vegetarians
.
New York, NY
:
Oxford University Press
,
2003
:
231
9
.

12.

Toohey
ML
,
Harris
MA
,
Williams
D
,
Foster
G
,
Schmidt
WD
,
Melby
CL
.
Cardiovascular disease risk factors are lower in African-American vegans compared to lacto-ovo-vegetarians
.
J Am Coll Nutr
1998
;
17
:
425
34
.

13.

De Biase
SG
,
Fernandes
SF
,
Gianini
RJ
,
Duarte
JL
.
Vegetarian diet and cholesterol and triglyceride levels
.
Arq Bras Cardiol
2007
;
88
:
35
9
.

14.

Haddad
EH
,
Berk
LS
,
Kettering
JD
,
Hubbard
RW
,
Peters
WR
.
Dietary intake and biochemical, hematologic, and immune status of vegans compared with nonvegetarians
.
Am J Clin Nutr
1999
;
70
(
suppl
):
586S
93S
.

15.

Larsson
CL
,
Johansson
GK
.
Young Swedish vegans have different sources of nutrients than young omnivores
.
J Am Diet Assoc
2005
;
105
:
1438
41
.

16.

Keinan-Boker
L
,
Peeters
PH
,
Mulligan
AA
, et al. 
Soy product consumption in 10 European countries: the European Prospective Investigation into Cancer and Nutrition (EPIC) study
.
Public Health Nutr
2002
;
5
:
1217
26
.

17.

Djoussé
L
,
Amett
DK
,
Coon
H
,
Province
MA
,
Moore
LL
,
Ellison
RC
.
Fruit and vegetable consumption and LDL cholesterol: the National Heart, Lung, and Blood Institute Family Heart Study
.
Am J Clin Nutr
2004
;
79
:
213
7
.

18.

Bazzano
LA
,
He
J
,
Ogden
LG
, et al. 
Fruit and vegetable intake and risk of cardiovascular disease in US adults: the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study
.
Am J Clin Nutr
2002
;
76
:
93
9
.

19.

Bazzano
LA
,
Serdula
MK
,
Liu
S
.
Dietary intake of fruits and vegetables and risk of cardiovascular disease
.
Curr Atheroscler Rep
2003
;
5
:
492
9
.

20.

Larsson
CL
,
Johansson
GK
.
Dietary intake and nutritional status of young vegans and omnivores in Sweden
.
Am J Clin Nutr
2002
;
76
:
100
6
.

21.

Kelly
JH
Jr
,
Sabate
J
.
Nuts and coronary heart disease: an epidemiological perspective
.
Br J Nutr
2006
;
96
(
suppl
):
S61
7
.

22.

Mellen
PB
,
Walsh
TF
,
Herrington
DM
.
Whole grain intake and cardiovascular disease: a meta-analysis
.
Nutr Metab Cardiovasc Dis
2008
;
18
:
283
90
.

23.

Fraser
GE
.
Associations between diet and cancer, ischemic heart disease, and all-cause mortality in non-Hispanic white California Seventh-day Adventists
.
Am J Clin Nutr
1999
;
70
(
suppl
):
532S
8S
.

24.

Liu
RH
.
Potential synergy of phytochemicals in cancer prevention: mechanism of action
.
J Nutr
2004
;
134
(
suppl
):
3479S
85S
.

25.

World Cancer Research Fund
.
Food, nutrition, physical activity, and the prevention of cancer: a global perspective
Washington, DC
:
American Institute for Cancer Research
,
2007
.

26.

Liu
RH
.
Health benefits of fruits and vegetables are from additive and synergistic combinations of phytochemicals
.
Am J Clin Nutr
2003
;
78
(
suppl
):
517S
20S
.

27.

Key
TJ
,
Fraser
GE
,
Thorogood
M
, et al. 
Mortality in vegetarians and nonvegetarians: detailed findings from a collaborative analysis of 5 prospective studies
.
Am J Clin Nutr
1999
;
70
(
suppl
):
516S
24S
.

28.

Outila
TA
,
Karkkainen
MU
,
Seppanen
RH
,
Lamberg-Allardt
CJ
.
Dietary intake of vitamin D in premenopausal, healthy vegans was insufficient to maintain concentrations of serum 25-hydroxyvitamin D and intact parathyroid hormone within normal ranges during the winter in Finland
.
J Am Diet Assoc
2000
;
100
:
434
41
.

29.

Pilz
S
,
Dobnig
H
,
Winklhofer-Roob
B
, et al. 
Low serum levels of 25-hydroxyvitamin D predict fatal cancer in patients referred to coronary angiography
.
Cancer Epidemiol Biomarkers Prev
2008
;
17
:
1228
33
.

30.

Holick
MF
.
Sunlight, UV-radiation, vitamin D and skin cancer: how much sunlight do we need?
Adv Exp Med Biol
2008
;
624
:
1
15
.

31.

Cross
AJ
,
Leitzmann
MF
,
Gail
MH
,
Hollenbeck
AR
,
Schatzkin
A
,
Sinha
R
.
A prospective study of red and processed meat intake in relation to cancer risk
.
PLoS Med
2007
;
4
:
e325
.

32.

Chan
JM
,
Wang
F
,
Holly
EA
.
Pancreatic cancer, animal protein and dietary fat in a population-based study, San Francisco Bay Area, California
.
Cancer Causes Control
2007
;
18
:
1153
67
.

33.

Park
SY
,
Murphy
SP
,
Wilkens
LR
,
Henderson
BE
,
Kolonel
LN
.
Legume and isoflavone intake and prostate cancer risk: the Multiethnic Cohort Study
.
Int J Cancer
2008
;
123
:
927
32
.

34.

Warri
A
,
Saarinen
NM
,
Makela
S
,
Hilakivi-Clarke
L
.
The role of early life genistein exposures in modifying breast cancer risk
.
Br J Cancer
2008
;
98
:
1485
93
.

35.

van der Pols
JC
,
Bain
C
,
Gunnell
D
,
Smith
GD
,
Frobisher
C
,
Martin
RM
.
Childhood dairy intake and adult cancer risk: 65-y follow-up of the Boyd Orr cohort
.
Am J Clin Nutr
2007
;
86
:
1722
9
.

36.

Jacobsen
BK
,
Knutsen
SF
,
Fraser
GE
.
Does high soy milk intake reduce prostate cancer incidence? The Adventist Health Study
.
Cancer Causes Control
1998
;
9
:
553
7
.

37.

Allen
NE
,
Key
T
,
Appleby
PN
, et al. 
Animal foods, protein, calcium and prostate cancer risk: the European Prospective Investigation into Cancer and Nutrition
.
Br J Cancer
2008
;
98
:
1574
81
.

38.

Qin
LQ
,
Xu
JY
,
Wang
PY
,
Tong
J
,
Hoshi
K
.
Milk consumption is a risk factor for prostate cancer in Western countries: evidence from cohort studies
.
Asia Pac J Clin Nutr
2007
;
16
:
467
76
.

39.

Chan
JM
,
Stampfer
MJ
,
Ma
J
,
Gann
PH
,
Garziano
JM
,
Giovannucci
EL
.
Dairy products, calcium, and prostate cancer risk in the Physician’s Health Study
.
Am J Clin Nutr
2001
;
74
:
549
54
.

40.

New
SA
.
Do vegetarians have a normal bone mass?
Osteoporos Int
2004
;
15
:
679
88
.

41.

Chiu
JF
,
Lan
SJ
,
Yang
CY
, et al. 
Long-term vegetarian diet and bone mineral density in postmenopausal Taiwanese women
.
Calcif Tissue Int
1997
;
60
:
245
9
.

42.

Lau
EMC
,
Kwok
T
,
Woo
J
,
Ho
SC
.
Bone mineral density in Chinese elderly female vegetarians, vegans, lacto-ovegetarians and omnivores
.
Eur J Clin Nutr
1998
;
52
:
60
4
.

43.

Chan
HHL
,
Lau
EMC
,
Woo
J
,
Lin
F
,
Sham
A
,
Leung
PC
.
Dietary calcium intake, physical activity and risk of vertebral fractures in Chinese
.
Osteoporos Int
1996
;
6
:
228
32
.

44.

Lau
E
,
Donnan
S
,
Barker
DJ
,
Cooper
C
.
Calcium intake and physical activity in fractured proximal femur in Hong Kong
.
BMJ
1988
;
297
:
1441
3
.

45.

Smith
AM
.
Veganism and osteoporosis: a review of the current literature
.
Int J Nurs Pract
2006
;
12
:
302
6
.

46.

Appleby
P
,
Roddam
A
,
Allen
N
,
Key
T
.
Comparative fracture risk in vegetarians and nonvegetarians in EPIC-Oxford
.
Eur J Clin Nutr
2007
;
61
:
1400
6
.

47.

Lanham-New
SA
.
Importance of calcium, vitamin D and vitamin K for osteoporosis prevention and treatment
.
Proc Nutr Soc
2008
;
67
:
163
76
.

48.

Yaegashi
Y
,
Onoda
T
,
Tanno
K
,
Kuribayashi
T
,
Sakata
K
,
Orimo
H
.
Association of hip fracture and intake of calcium, magnesium, vitamin D, and vitamin K
.
Eur J Epidemiol
2008
;
23
:
219
25
.

49.

New
SA
.
Intake of fruit and vegetables: implications for bone health
.
Proc Nutr Soc
2003
;
62
:
889
99
.

50.

Cassidy
A
,
Albertazzi
P
,
Lise Nielsen
I
, et al. 
Critical review of health effects of soyabean phyto-oestrogens in post-menopausal women
.
Proc Nutr Soc
2006
;
65
:
76
92
.

51.

Arnett
TR
,
Spowage
M
.
Modulation of the resorptive activity of rat osteoclasts by small changes in extracellular pH near the physiological range
.
Bone
1996
;
18
:
277
9
.

52.

Buclin
T
,
Cosma
M
,
Appenzeller
M
, et al. 
Diet acids and alkalis influence calcium retention in bone
.
Osteoporos Int
2001
;
12
:
493
9
.

53.

Tucker
KL
,
Hannan
MT
,
Kiel
DP
.
The acid-base hypothesis: diet and bone in the Framingham Osteoporosis Study
.
Eur J Nutr
2001
;
40
:
231
7
.

54.

New
SA
,
Bolton-Smith
C
,
Grubb
DA
,
Reid
DM
.
Nutritional influences on mineral density: a cross-sectional study in premenopausal women
.
Am J Clin Nutr
1997
;
65
:
1831
9
.

55.

Vergnaud
P
,
Garnero
P
,
Meunier
PJ
,
Breart
G
,
Kamihagi
K
,
Delmas
PD
.
Undercarboxylated osteocalcin measured with a specific immunoassay predicts hip fracture in elderly women: the EPIDOS Study
.
J Clin Endocrinol Metab
1997
;
82
:
719
24
.

56.

Szulc
P
,
Arlot
M
,
Chapuy
MC
,
Duboeuf
F
,
Muenier
PJ
,
Delmas
PD
.
Serum undercarboxylated osteocalcin correlates with hip bone mineral density in elderly women
.
J Bone Miner Res
1994
;
9
:
1591
5
.

57.

Feskanich
D
,
Weber
P
,
Willett
WC
,
Rockett
H
,
Booth
SL
,
Colditz
GA
.
Vitamin K intake and hip fractures in women: a prospective study
.
Am J Clin Nutr
1999
;
69
:
74
9
.

58.

Booth
SL
,
Tucker
KL
,
Chen
H
, et al. 
Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women
.
Am J Clin Nutr
2000
;
71
:
1201
8
.

59.

Ma
DF
,
Qin
LQ
,
Wang
PY
,
Katoh
R
.
Soy isoflavone intake increases bone mineral density in the spine of menopausal women: meta-analysis of randomized controlled trials
.
Clin Nutr
2008
;
27
:
57
64
.

60.

Ma
DF
,
Qin
LQ
,
Wang
PY
,
Katoh
R
.
Soy isoflavone intake inhibits bone resorption and stimulates bone formation in menopausal women: meta-analysis of randomized controlled trials
.
Eur J Clin Nutr
2008
;
62
:
155
61
.

61.

Marini
H
,
Minutoli
L
,
Polito
F
, et al. 
Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial
.
Ann Intern Med
2007
;
146
:
839
47
.

62.

Burdge
GC
,
Finnegan
YE
,
Minihane
ME
,
Williams
CM
,
Wootton
SA
.
Effect of altered dietary n-3 fatty acid intake upon plasma lipid fatty acid composition, conversion of [13C]alpha-linolenic acid to longer-chain fatty acids and partitioning towards beta-oxidation in older men
.
Br J Nutr
2003
;
90
:
311
21
.

63.

Burdge
GC
,
Wootton
SA
.
Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women
.
Br J Nutr
2002
;
88
:
411
20
.

64.

Rosell
MS
,
Lloyd-Wright
Z
,
Appleby
PN
,
Sanders
TAB
,
Allen
NE
,
Key
TJ
.
Long-chain n-3 polyunsaturated fatty acids in plasma in British meat-eating, vegetarian, and vegan men
.
Am J Clin Nutr
2005
;
82
:
327
34
.

65.

Food and Nutrition Board, Institute of Medicine of the National Academies
.
Dietary fats: total fats and fatty acids. Dietary Reference Intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids (macronutrients).
Washington, DC
:
National Academy Press
,
2005
:
422
541
.

66.

Geppert
J
,
Kraft
V
,
Demmelmair
H
,
Koletzko
B
.
Microalgal docosahexaenoic acid decreases plasma triacylglycerol in normolipidaemic vegetarians: a randomised trial
.
Br J Nutr
2006
;
95
:
779
86
.

67.

Sanders
TA
,
Gleason
K
,
Griffen
B
,
Miller
GJ
.
Influence of an algal triacylglycerol containing docosahexaenoic acid (22:6n-3) and docosapentaenoic acid (22:5n-6) on cardiovascular risk factors in healthy men and women
.
Br J Nutr
2006
;
95
:
525
31
.

68.

Webb
AR
,
Kline
L
,
Holick
MF
.
Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin
.
J Clin Endocrinol Metab
1988
;
67
:
373
8
.

69.

Trang
HM
,
Cole
DE
,
Rubin
LA
,
Pierratos
A
,
Siu
S
,
Vieth
R
.
Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2
.
Am J Clin Nutr
1998
;
68
:
854
8
.

70.

Craig
WJ
.
Iron status of vegetarians
.
Am J Clin Nutr
1994
;
59
(
suppl
):
1233S
7S
.

71.

Wilson
AK
,
Ball
MJ
.
Nutrient intake and iron status of Australian male vegetarians
.
Eur J Clin Nutr
1999
;
53
:
189
94
.

72.

Majchrzak
D
,
Singer
I
,
Manner
M
, et al. 
B-vitamin status and concentrations of homocysteine in Austrian omnivores, vegetarians and vegans
.
Ann Nutr Metab
2006
;
50
:
485
91
.

73.

McNulty
H
,
Pentieva
K
,
Hoey
L
,
Ward
M
.
Homocysteine, B-vitamins and CVD
.
Proc Nutr Soc
2008
;
67
:
232
7
.

74.

McLean
RR
,
Jacques
PF
,
Selhub
J
, et al. 
Plasma B vitamins, homocysteine and their relation with bone loss and hip fracture in elderly men and women
.
J Clin Endocrinol Metab
2008
;
93
:
2206
12
.

75.

Food and Nutrition Board, Institute of Medicine
.
Vitamin B12: Dietary Reference Intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid
.
Washington, DC
:
Biotin, and Choline. National Academy Press
,
1998
;
306
56
.

76.

Hunt
JR
.
Moving towards a plant-based diet: are iron and zinc at risk?
Nutr Rev
2002
;
60
:
127
34
.

77.

Gibson
RS
.
Content and bioavailability of trace elements in vegetarian diets
.
Am J Clin Nutr
1994
;
59
(
suppl
):
1223S
32S
.

78.

Zhao
Y
,
Martin
BR
,
Weaver
CM
.
Calcium bioavailability of calcium carbonate fortified soymilk is equivalent to cow’s milk in young women
.
J Nutr
2005
;
135
:
2379
82
.

79.

Andon
MB
,
Peacock
M
,
Kanerva
RL
,
De Castro
JA
.
Calcium absorption from apple and orange juice fortified with calcium citrate malate (CCM)
.
J Am Coll Nutr
1996
;
15
:
313
6
.

80.

Messina
V
,
Melina
V
,
Mangels
AR
.
A new food guide for North American vegetarians
.
J Am Diet Assoc
2003
;
103
:
771
5
.

81.

Barnard
ND
,
Cohen
J
,
Jenkins
DJA
, et al. 
A low-fat vegan diet improves glycemic control and cardiovascular risk factors in a randomized clinical trial in individuals with type diabetes
.
Diabetes Care
2006
;
29
:
1777
83
.

82.

Brathwaite
N
,
Fraser
HS
,
Modeste
N
,
Broome
H
,
King
R
.
Obesity, diabetes, hypertension, and vegetarian status among Seventh-day Adventists in Barbados: preliminary results
.
Ethn Dis
2003
;
13
:
34
9
.

83.

Rajaram
S
,
Sabaté
J
.
Preface
.
Am J Clin Nutr
2009
;
89
(
suppl
):
1541S
2S
.

84.

Jacobs
DR
Jr
,
Gross
MD
,
Tapsell
LC
.
Food synergy: an operational concept for understanding nutrition
.
Am J Clin Nutr
2009
;
89
(
suppl
):
1543S
8S
.

85.

Jacobs
DR
Jr
,
Haddad
EH
,
Lanou
AJ
,
Messina
MJ
.
Food, plant food, and vegetarian diets in the US dietary guidelines: conclusions of an expert panel
.
Am J Clin Nutr
2009
;
89
(
suppl
):
1549S
52S
.

86.

Lampe
JW
.
Interindividual differences in response to plant-based diets: implications for cancer risk
.
Am J Clin Nutr
2009
;
89
(
suppl
):
1553S
7S
.

87.

Simon
JA
,
Chen
Y-H
,
Bent
S
.
The relation of α-linolenic acid to the risk of prostate cancer: a systematic review and meta-analysis
.
Am J Clin Nutr
2009
;
89
(
suppl
):
1558S
64S
.

88.

Pierce
JP
,
Natarajan L
,
Caan
BJ
, et al. 
Dietary change and reduced breast cancer events among women without hot flashes after treatment of early-stage breast cancer: subgroup analysis of the Women’s Healthy Eating and Living Study
.
Am J Clin Nutr
2009
;
89
(
suppl
):
1565S
71S
.

89.

Newby
PK
.
Plant foods and plant-based diets: protective against childhood obesity?
Am J Clin Nutr
2009
;
89
(
suppl
):
1572S
87S
.

90.

Barnard
ND
,
Cohen
J
,
Jenkins
DJA
, et al. 
A low-fat vegan diet and a conventional diabetes diet in the treatment of type 2 diabetes: a randomized, controlled, 74-wk clinical trial
.
Am J Clin Nutr
2009
;
89
(
suppl
):
1588S
96S
.

91.

Mangat
I
.
Do vegetarians have to eat fish for optimal crdiovascular protection?
Am J Clin Nutr
2009
;
89
(
suppl
):
1597S
601S
.

92.

Willis
LM
,
Shukitt-Hale
B
,
Joseph
JA
.
Modulation of cognition and behavior in aged animals: role for antioxidant- and essential fatty acid–rich plant foods
.
Am J Clin Nutr
2009
;
89
(
suppl
):
1602S
6S
.

93.

Fraser
GE
.
Vegetarian diets: what do we know of their effects on common chronic diseases?
Am J Clin Nutr
2009
;
89
(
suppl
):
1607S
12S
.

94.

Key
TJ
,
Appleby
PN
,
Spencer
EA
,
Travis
RC
,
Roddam
AW
,
Allen
NE
.
Cancer incidence in vegetarians: results from the European Prospective Investigation into Cancer and Nutrition (EPIC-Oxford)
.
Am J Clin Nutr
2009
;
89
(
suppl
):
1620S
6S
.

95.

Key
TJ
,
Appleby
PN
,
Spencer
EA
,
Travis
RC
,
Roddam
AW
,
Allen
NE
.
Mortality in British vegetarians: results from the European Prospective Investigation into Cancer and Nutrition (EPIC-Oxford)
.
Am J Clin Nutr
2009
;
89
(
suppl
):
1613S
9S
.

96.

Weaver
CM
.
Should dairy be recommended as part of a healthy vegetarian diet? Point
.
Am J Clin Nutr
2009
;
89
(
suppl
):
1634S
7S
.

97.

Lanou
AJ
.
Should dairy be recommended as part of a healthy vegetarian diet? Counterpoint
.
Am J Clin Nutr
2009
;
89
(
suppl
):
1638S
42S
.

98.

Sabaté
J
,
Ang
Y
.
Nuts and health outcomes: new epidemiologic evidence
.
Am J Clin Nutr
2009
;
89
(
suppl
):
1643S
8S
.

99.

Ros
E
.
Nuts and novel biomarkers of cardiovascular disease
.
Am J Clin Nutr
2009
;
89
(
suppl
):
1649S
56S
.

100.

Rajaram
S
,
Haddad
EH
,
Mejia
A
,
Sabaté
J
.
Walnuts and fatty fish influence different serum lipid fractions in normal to mildly hyperlipidemic individuals: a randomized controlled study
.
Am J Clin Nutr
2009
;
89
(
suppl
):
1657S
63S
.

101.

Lampe
JW
.
Is equol the key to the efficacy of soy foods?
Am J Clin Nutr
2009
;
89
(
suppl
):
1664S
7S
.

102.

Badger
TM
,
Gilchrist
JM
,
Pivik
RT
, et al. 
The health implications of soy infant formula
.
Am J Clin Nutr
2009
;
89
(
suppl
):
1668S
72S
.

103.

Messina
M
,
Wu
AH
.
Perspectives on the soy–breast cancer relation
.
Am J Clin Nutr
2009
;
89
(
suppl
):
1673S
9S
.

104.

Lönnerdal
B
.
Soybean ferritin: implications for iron status of vegetarians
.
Am J Clin Nutr
2009
;
89
(
suppl
):
1680S
5S
.

105.

Chan
J
,
Jaceldo-Siegl
K
,
Fraser
GE
.
Serum 25-hydroxyvitamin D status of vegetarians, partial vegetarians, and nonvegetarians: the Adventist Health Study-2
.
Am J Clin Nutr
2009
;
89
(
suppl
):
1686S
92S
.

106.

Elmadfa
I
,
Singer
I
.
Vitamin B-12 and homocysteine status among vegetarians: a global perspective
.
Am J Clin Nutr
2009
;
89
(
suppl
):
1693S
8S
.

107.

Marlow
HJ
,
Hayes
WK
,
Soret
S
,
Carter
RL
,
Schwab
ER
,
Sabaté
J
.
Diet and the environment: does what you eat matter?
Am J Clin Nutr
2009
;
89
(
suppl
):
1699S
703S
.

108.

Carlsson-Kanyama
A
,
González
AD
.
Potential contributions of food consumption patterns to climate change
.
Am J Clin Nutr
2009
;
89
(
suppl
):
1704S
9S
.

109.

Eshel
G
,
Martin
PA
.
Geophysics and nutritional science: toward a novel, unified paradigm
.
Am J Clin Nutr
2009
;
89
(
suppl
):
1710S
6S
.