- Vegetarian Cohorts and Standardized Mortality
- Meta-Analysis of Mortality (1999)
- Meta-Analysis of Mortality (2012)
- Stroke Risk in Taiwanese Vegetarians (2020)
- EPIC-Oxford: Ischemic Heart Disease and Stroke Incidence (2019)
- EPIC-Oxford: Gallstones (2017)
- EPIC-Oxford: Mortality Rates (2015)
- EPIC-Oxford: Heart Disease Incidence (2013)
- EPIC-Oxford: Cataracts (2011)
- EPIC-Oxford: Diverticular Disease (2011)
- EPIC-Oxford: Heart Disease Mortality (2009)
- EPIC-Oxford: Bone Fractures (2007)
- EPIC-Oxford: Preliminary Mortality Rates (2003)
- British Mortality (2002)
- Adventist Health Study-2
- Adventist Health Study
- Heidelberg Study (German Vegetarians)
Vegetarian Cohorts and Standardized Mortality
The table below lists the main cohort studies designed to examine differences between vegetarians and meat-eaters. They recruited people with similar lifestyles but different diets.
Most of the cohorts reported a standardized mortality ratio (SMR) which is the death rate of the study population compared to the greater population of their region. The cohort SMRs show about half the mortality rate of people under age 90. The researchers attributed most of the differences to lower smoking and the healthy volunteer effect, but some may have been due to a healthier diet (3, 8).
|Cohort Studies with Large Numbers of Vegetarians|
|Study||Country||Years||Number of Vegans||SMR|
|Health Food Shoppers||UK||1976-88||.563|
|Adventist Health Study-2||USA||2002 –||5,500||.6726|
These cohort studies are observational. They provide both cross-sectional and prospective data to measure differences between groups made up of individuals who are self-motivated to follow particular eating patterns. Because the participants haven’t been randomized to the different eating patterns, and their diets aren’t controlled beyond a broad classification, it’s harder to determine cause and effect than for randomized clinical trials. Observational studies are more practical than clinical trials—they cost less per person and make it easier to follow people for longer periods of time which tends to be required for measuring differences in disease rates. For information on the types of nutrition studies and their pros and cons, please see Basics of Nutrition Research.
Meta-Analysis of Mortality (1999)
A 1999 meta-analysis on vegetarian mortality used prospective data from the Adventist Mortality, Adventist Health, Oxford Vegetarian, and Heidelberg studies to compare mortality rates between types of vegetarians and non-vegetarians (3). There weren’t many significant differences between diet groups, including none between the vegans and regular meat-eaters for any cause of death.
|Meta-Analysis of Vegetarian Mortality (1999)3|
|All Causes||1.00||.84 (.77-.90)||.82 (.77-.96)||.84 (.74-.96)||1.00 (.70-1.44)|
|Ischemic Heart Disease||1.00||.80 (.69-.93)||.66 (.48-.90)||.66 (.52-.83)||.74 (.46-1.21)|
|Stroke||1.00||.97 (.75-1.25)||1.04 (.65-1.64)||.87 (.66-1.13)||.70 (.25-1.98)|
|Colorectal Cancer||1.00||1.14 (.72-1.82)||1.00 (.42-2.38)||1.10 (.79-1.54)||.83 (.11-6.17)|
|Breast Cancer||1.00||.97 (.56-1.71)||1.50 (.74-3.04)||.75 (.49-1.14)||no cases|
|Prostate Cancer||1.00||1.06 (.60-1.89)||1.25 (.30-5.22)||.75 (.47-1.21)||no cases|
|Adjusted for age, sex, smoking status, and study.|
Meta-Analysis of Mortality (2012)
Although a 2012 meta-analysis by Huang et al. (11) is more recent, it may not be as reliable as the 1999 meta-analysis because it includes a 1984 study on Zen priests (12) who were mostly semi-vegetarian and which used a standardized mortality ratio comparing all the Zen priests to the greater population rather than comparing the semi-vegetarians to the non-vegetarians within the same group. The Heidelberg Study results were also included and its comparison group were semi-vegetarians, which means there were semi-vegetarians in both the “vegetarian” and “non-vegetarian” groups in this meta-analysis. While not ideal, it should have biased the results against finding a beneficial effect of a vegetarian diet. In its favor, the 2012 meta-analysis includes data from EPIC-Oxford that wasn’t available for the 1999 meta-analysis.
|Meta-Analysis of Vegetarian Mortality (2012)|
|Mortality Rate of Vegetarians|
|All Causes||0.91 (0.66, 1.16)|
|Ischemic Heart Disease||0.71 (0.56, 0.87)|
|Cerebrovascular Disease (Stroke)||0.88 (0.70, 1.06)|
|Combined Ischemic Heart and Circulatory Disease||0.84 (0.54, 1.14)|
|Cancer Incidence||0.82 (0.67, 0.97)|
Stroke Risk in Taiwanese Vegetarians (2020)
A 2020 study combined two Taiwanese prospective cohorts resulting in 13,352 total participants, of whom 4,143 of were vegetarian (27). After 8 years of follow-up (A), vegetarians had a lower risk of both ischemic and hemorrhagic stroke.
In Cohort 1, ischemic stroke was lower in vegetarians (HR 0.26, 95% CI 0.08–0.88) and hemorrhagic stroke was not analyzed due to few events. In Cohort 2, ischemic stroke (HR 0.41, 95% CI 0.19–0.88) and hemorrhagic stroke (HR 034, 95% CI 0.12–1.00) were lower in vegetarians.
Lower stroke risk was seen only in vegetarians with low vitamin B12 intake, defined as <2.4 μg per day (P=0.046). Because vitamin B12 is a marker of animal product intake, the most likely explanation is that a higher animal product intake attenuated the benefits of a vegetarian diet.
EPIC-Oxford: Ischemic Heart Disease and Stroke Incidence (2019)
A September 2019 report from the EPIC-Oxford study garnered much media attention. The study found that vegetarians had a 20% higher rate of total stroke than meat-eaters, equivalent to 3 more cases of total stroke per 1,000 people over a 10 year period, mostly due to a higher rate of hemorrhagic stroke (21). In this study, “vegetarians” included vegans (12.7% of the vegetarians).
The study also found that vegetarians had a 22% lower risk of ischemic heart disease than meat-eaters (a difference equivalent to 10 fewer cases of ischemic heart disease per 1,000 people over 10 years), which is in line with existing evidence. And vegetarians didn’t have a significantly higher risk of ischemic stroke than meat-eaters.
Hemorrhagic stroke is caused by bleeding in the brain, which is distinct from ischemic stroke, the more common type, which is caused by a blockage of blood flow to the brain.
A major risk factor for hemorrhagic stroke is high blood pressure, but vegetarians in this study had slightly lower blood pressure than meat-eaters. Research also suggests that low total and LDL cholesterol may increase the risk of hemorrhagic stroke (22, 23, 24), and vegetarians had lower levels of both in this study.
Participants were separated into more specific dietary groups in the table below.
|Incidence of Cardiovascular Disease in EPIC-Oxford (2019)21|
|Heart Attack||1.00||1.00 (.78-1.26)||.91 (.74-1.12)||.77 (.46-1.27)|
|Ischemic Heart Disease||1.00||.87 (.77-.99)||.77 (.69-.86)||.82 (.64-1.05)|
|Total Stroke||1.00||1.14 (.94-1.38)||1.17 (1.00-1.38)||1.35 (.95-1.92)|
|18 years follow-up. Adjusted for age, sex, method of recruitment, region, year of recruitment, education, Townsend deprivation index, smoking, alcohol, physical activity, supplement use, oral contraception (women), hormone replacement therapy (women).|
EPIC-Oxford: Gallstones (2017)
After a mean follow-up time of 13.8 years and after adjusting for a number of variables including smoking and alcohol intake, EPIC-Oxford found no significant difference in the risk of symptomatic gallstone disease in vegetarians compared to meat-eaters (20). When a further adjustment was made for body mass index (BMI), vegetarians had a higher risk (1.22, 1.06-1.41) for symptomatic gallstone disease compared to non-vegetarians. Among both vegetarians and non-vegetarians, those with the highest BMI had the highest risk of developing the disease.
EPIC-Oxford: Mortality (2015)
In their paper from 2015 (19), the mortality rate before age 90 in EPIC-Oxford was no different between vegetarians (including vegans) and regular meat-eaters (1.02, 0.94-1.10). Vegetarians had lower rates of mortality from pancreatic cancer (0.48, 0.28-0.82) and lymphatic cancer (0.50, 0.32-0.79). Semi-vegetarians had lower rates of death from pancreatic cancer (0.55, 0.36-.86). Pesco-vegetarians had lower death rates from all cancers (0.82, 0.70-0.97) but higher rates of cardiovascular disease (1.22, 1.02-1.46).
In the main analyses in the above paragraph, some participants were recategorized based on a change in their diets. The researchers did a second analysis in which participants who changed their diets were removed and found an 8% reduced risk of early death in vegetarians (0.92, 0.84-0.99). Limiting the results further, to deaths before age 75, strengthened the finding (0.86, 0.77-0.97).
When vegans were separated from other vegetarians, there were no statistically significant differences in mortality rates for the six large categories of death. Eliminating participants who had changed diet categories didn’t significantly change the results. The small number of deaths among vegans (166) as compared to the rest of the cohort (1,929) may have contributed to a lack of statistical significance.
EPIC-Oxford: Heart Disease Incidence (2013)
Heart disease rates of all vegetarians compared to all non-vegetarians were calculated for EPIC-Oxford from 1993 until 2009 (13). These participants were all thought to be free of heart disease at the beginning of the study. The results showed that vegetarians had a statistically significant, ~30% reduced risk of heart disease. This finding held after adjusting for body mass index (BMI) and removing the first two years of follow-up.
The researchers believed the difference in heart disease rates to be due mainly to the lower non-HDL cholesterol levels and systolic blood pressure rates of the vegetarians.
|Risk of Heart Disease in Vegetarians Compared to Non-vegetarians in EPIC-Oxford (2013)13|
|Model One: age, smoking, alcohol, physical activity, education,
socioeconomic status, oral contraceptives, hormone replacement therapy
|0.68 (0.58, 0.81)|
|Model One plus body mass index||0.72 (0.61, 0.85)|
|Model One minus first 2 years of follow-up||0.69 (0.58, 0.82)|
EPIC-Oxford: Diverticular Disease (2011)
After a mean follow-up time of 11.6 years, EPIC Oxford found that vegetarians had a 31% lower risk of diverticular disease compared with meat-eaters (0.69, 0.55-0.86; 14).
EPIC-Oxford: Cataracts (2011)
In a case-control analysis of EPIC-Oxford participants ≥40 years old, a significantly lower risk of cataracts was found in vegetarians than meat-eaters (9). Vegans had a 40% lower risk of cataracts than those eating more than 100 g/day of meat.
|Incidence of Cataracts in EPIC-Oxford (2011)9|
|High Meat||Medium Meat||Low Meat||Pesco||Lacto-Ovo||Vegan|
|Incidence||1.00||.96 (.84-1.11)||.85 (.72-.99)||.79 (.65-.97)||.70 (.58-.84)||.60 (.38-.96)|
|11.4 years follow-up. Adjusted for age, smoking, ethnicity, self-reported prior high blood pressure, long-term medical treatment, hormone replacement therapy, sex, method of recruitment, and region. Meat intake: high is ≥100 g/d, medium is 50-99 g/d, low is >50 g/d.|
EPIC-Oxford: Heart Disease Mortality (2009)
After 10.7 years of follow-up, the results of death from heart disease, stroke, and all causes were released from EPIC-Oxford in 2009 (8). There were no significant differences between vegetarians and meat-eaters for deaths from any of these diseases. This was likely due to the relatively few deaths from heart disease overall, not allowing for statistical power. The authors stated:
Average meat intake among the meat-eaters was only moderate, at 79 g/d in men and 67 g/d in women; these intakes are much lower than those reported in the National Diet and Nutrition Survey for the United Kingdom. Consumption of vegetables and fruit was higher among vegetarians than among non-vegetarians, but the differences were not large (< 20%). Thus, if high intakes of meat had an adverse effect and high intakes of fruit and vegetables had a beneficial effect, the relatively low meat intake and high fruit and vegetable intake of the non-vegetarians in this cohort could reduce the chance of observing lower mortality rates in the vegetarians than in the non-vegetarians.
EPIC-Oxford: Bone Fractures (2007)
In a 2007 analysis of bone fractures from EPIC-Oxford, vegans had a 30% higher fracture rate than meat-eaters (RR 1.30, CI 1.02-1.66) after adjusting for smoking, alcohol, body mass index, walking, cycling, vigorous exercise, other exercise, physical activity at work, marital status, parity and hormone replacement therapy (10). When the results were adjusted for calcium intake, the vegans no longer had a higher fracture rate. Among the subjects whse diets contained ≥525 mg of calcium a day (only 55% of the vegans compared to about 95% of the other diet groups), vegans had the same fracture rates as the other diet groups.
More information can be found in the article Calcium Part 2—Research.
Epic-Oxford: Preliminary Mortality Results (2003)
In 2003, preliminary results from EPIC-Oxford (Oxford component of the European Prospective Investigation into Cancer and Nutrition) comparing death rates of 46,562 subjects were reported (7). About 33% of the subjects were vegetarian (including many vegans). The results showed no statistically significant differences between the vegetarians and non-vegetarians in any of the mortality categories which included cancer, circulatory disease, ischemic heart disease, cerebrovascular disease (stroke), all other causes, and all causes combined.
British Mortality (2002)
In 2002, the final death rate ratios were published from the Health Food Shoppers Study and the Oxford Vegetarian Study (15). Because data on these populations have been published in the 1999 meta-analysis and many of the subjects went on to participate in EPIC-Oxford, I will not repeat the findings here.
However, there was one finding that has not been published elsewhere and it was the death rate ratio for “mental and neurological diseases.” The Health Food Shoppers Study showed no difference between vegetarians and non-vegetarians, but the Oxford Vegetarian study found vegetarians to have 2.5 times the number of deaths (2.46, 1.21-5.01). After excluding the first five years of follow-up, the death risk ratio went down to 2.21 (1.02 – 4.78). While the rate was statistically significant, and the difference was quite large, the confidence interval is very wide, indicating that it could possibly be due to random chance. Another likely explanation is that vitamin B12 deficiency was leading to neurological disorders. A less likely possibility, but one the that cannot be completely ruled out, is that vegetarians were suffering from low DHA levels.
Two analyses from the Adventist Health Study compared dementia in vegetarians to non-vegetarians, and were published in the same paper (16). The subjects had to have been vegetarian for at least 20 years. In the first, 68 vegans, 68 lacto-ovo vegetarians, and 136 omnivores were matched for age, gender, and zip code. The non-vegetarians were two to three times as likely to have dementia, though the finding was not statistically significant until previous meat-consumption was taken into account and even then it was just borderline. No difference in dementia was found between vegetarians and non-vegetarians among a second group of unmatched subjects. A 2013 report on mortality from Adventist Health Study-2 found no difference between vegetarians and non-vegetarians for death rates from neurologic diseases, though pesco- and semi-vegetarians were included in the “vegetarian” group (17).
Based on the fact that Seventh-day Adventists have long been aware that vitamin B12 can’t be found in plants, and are a tight community with strong support for vegetarianism, vitamin B12 deficiency may have been less likely in the Adventist Health Study than in British vegetarians.
Adventist Health Study-2 (AHS-2)
AHS-2: CVD Mortality and Protein Source
In an analysis published in 2018, researchers found significantly higher rates of cardiovascular deaths associated with meat protein intake compared to nut and seed protein intake among a sample of 81,337 adults from the Adventist Health Study-2 (25). The multivariate-adjusted hazard ratios for cardiovascular mortality were 1.61 (98.75% CI, 1.12 2.32; P-trend <0.001) for the meat protein factor and 0.60 (98.75% CI, 0.42 0.86; P-trend <0.001) for the nuts and seeds protein factor (comparing highest versus lowest quintiles).
No significant associations were found for grains, legumes, fruits and vegetables, or processed foods. Researchers controlled for covariates including vegan diet, unsaturated fat, saturated fat, fiber, sodium, and antioxidant intake.
After accounting for these covariates, the association between cardiovascular deaths and type of protein remained statistically significant. Authors suggested there is something unique about the type of protein (such as amino acid composition), regardless of other dietary components, that impacts cardiovascular health.
AHS-2: Mortality (2013)
In 2013, death rates for the first 5.8 years of Adventist Health Study-2 were released (17). Results are in the table below.
|Death Rates in Adventist Health Study-217|
|All Causes||1.00||.92 (.75-1.13)||.81 (.69-.94)||.91 (.82-1.00)||.85 (.73-1.01)|
|All Cardiovascular Disease||1.00||.85 (.63-1.16)||.80 (.62-1.03)||.90 (.76-1.06)||.91 (.71-1.16)|
|Ischemic Heart Disease||1.00||.92 (.57-1.51)||.65 (.43-.97)||.82 (.62-1.06)||.90 (.60-1.33)|
|Cancer||1.00||.94 (.66-1.35)||.94 (.72-1.22)||.90 (.75-1.09)||.92 (.68-1.24)|
|Other Causes||1.00||.99 (.72-1.36)||.71 (.54-.94)||.91 (.77-1.07)||.74 (.56-.99)|
|Adjusted for age, race, smoking, exercise, personal income, educational level, marital status, alcohol, region, sleep, sex, menopausal status, and hormone therapy. Further adjusting for body mass index and energy intake didn’t substantially impact results (data not shown).|
Breaking the results down by sex indicated a significant benefit for cardiovascular disease for male vegans 0.58 (0.38-0.89) but not female vegans 1.18 (0.88-1.60). Analysis within the other causes category showed reductions in mortality from diabetes mellitus and renal failure for vegetarians.
Diet was measured at baseline and not re-assessed again (as distinct from EPIC-Oxford which measured diet numerous times during the study). The researchers believed that the short follow-up time of 5.8 years would bias the results towards finding no differences between diet groups.
In comparing their findings to British vegetarians, the researchers said:
The lack of similar findings in British vegetarians remains interesting, and this difference deserves careful study. In both cohorts, the non-vegetarians are a relatively healthy reference group. In both studies, the nutrient profiles of vegetarians differ in important ways from those of non-vegetarians, with vegetarians (especially vegans) consuming less saturated fat and more fiber. It appears that British vegetarians and US Adventist vegetarians eat somewhat differently. For instance, the vegetarians in our study consume more fiber and vitamin C than those of the EPIC-Oxford cohort: mean dietary fiber in EPIC-Oxford vegans was 27.7 g/d in men and 26.4 g/d in women compared with 45.6 g/d in men and 47.3 g/d in women in AHS-2 vegans; mean vitamin C in EPIC-Oxford vegans was 125 mg/d in men and 143 mg/d in women compared with 224 mg/d in men and 250 mg/d in women in AHS-2 vegans. Individuals electing vegetarian diets for ethical or environmental reasons may eat differently from those who choose vegetarian diets primarily for reasons of perceived superiority for health promotion. We believe that perceived healthfulness of vegetarian diets may be a major motivator of Adventist vegetarians.
In 2013, rates of hypothyroidism in AHS-2 were published (18). Rates were reported both cross-sectionally at baseline and prospectively after about 4-6 years of follow-up (exact number not specified).
Results are in the table below. For the cross-sectional arm, lacto-ovo vegetarians were more likely to have been treated for hypothyroidism in the previous year, although the statistical significance was not strong. There were no other statistically significant findings, although vegans had a trend towards less hypothyroidism in the prospective arm.
According to the authors, “While vegan diets are associated with lower body weight, which may protect against hypothyroidism, the lower risk among vegans existed even after controlling for [body mass index] and potential demographic confounders.” It would have been interesting to see what the results were without adjusting for body mass index, but that information wasn’t reported.
Interestingly, adding salt to foods more often was associated with increased hypothyroidism among the entire population. Whether the salt was iodized was not determined (it likely was since most table salt in the U.S. is iodized).
Hypothyroidism Rates in Adventist Health Study-2 (2013)18
|semi-vegetarian||1.04 (0.91-1.19)||0.87 (0.65-1.17)|
|pesco-vegetarian||1.02 (0.90-1.15)||0.87 (0.65-1.17)|
|lacto-ovo vegetarian||1.09 (1.01-1.18)||1.07 (0.91-1.24)|
|vegan||0.89 (0.78-1.01)||0.78 (0.59-1.03)|
|Results adjusted for age, body mass index, gender, race, income, education, salt use.|
Adventist Health Study
- Data collected from 1976-1988
- 34,192 participants, members of the Seventh-day Adventist church
- 29% were vegetarian; 7-10% of the vegetarians were vegan.
|Table 4. Adventist Health Study Results|
|Heart disease||38% Lower for Men||No Difference for Women|
|Overall mortality||Lived 3.21 more yrs||Lived 2.52 more yrs|
|aBMI—Body Mass Index. A measure of healthy body weight. Lower than 20 is underweight, while ≥ 25 is overweight.|
Compared to the non-vegetarians, vegetarians had about:
- 1/2 the high blood pressure and diabetes
- 2/3 the rheumatoid arthritis
Life expectancies in the Adventist Health Study were published in 2001 (2). They showed that white, non-Hispanic Seventh-day Adventists live longer than other white Californians (7.28 more years for men, 4.42 more years for women). According to the researchers, this group of Seventh-day Adventists was the longest-lived, formally studied population in the world (with an average lifespan of 78.5 years for men, 82.3 for women).
The following variables were shown to increase life expectancy:
- vegetarian diet
- eating nuts regularly
- physical activity
- lower body weight
- no smoking
Heidelberg Study (German Vegetarians)
In 2005, results from 21 years of follow-up of the Heidelberg Study were published (5). The 1999 Meta-Analysis included only 11 years of follow-up from this population.
There were only 60 vegans in the Heidelberg Study, which was 3% of the study group. The authors state, “Being a vegan was associated with a higher mortality risk (1.59; 95% CI (confidence interval), 0.98-2.59) than being a lacto-ovo vegetarian (1.08; 95% CI, 0.86-1.34), when compared with non-vegetarians with moderate meat/ fish consumption, accounting for all other variables (data not shown).”
As you can see, these findings were not statistically significant, but they were close for the vegans. Also note that these “non-vegetarians” were semi-vegetarians, eating very little meat. It wouldn’t surprise me to find out these vegans did not do much to supplement their diet with vitamin B12.
Other results of interest are shown in Table 5.
|Table 5. Heidelberg Study Results|
|Activity||Rates and Confidence Interval||Notes|
|Ischemic heart disease|
|Ischemic heart disease|
The authors had the following to say about physical activity:
Our findings corroborate epidemiologic evidence indicating that regular and vigorous physical activity is an effective means of preventing circulatory diseases and cancers at different sites.
Last updated March 2018
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21. Tong TYN, Appleby PN, Bradbury KE, et al. Risks of ischaemic heart disease and stroke in meat eaters, fish eaters, and vegetarians over 18 years of follow-up: results from the prospective EPIC-Oxford study. BMJ. 2019 Sep 4;366:l4897.
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