Fruit and vegetable intake and the risk of cardiovascular disease, total cancer and all-cause mortality - a systematic review and dose-response meta-analysis of prospective studies

There was a 28% reduction in the relative risk of stroke at 500 g/day of vegetables.

“28% reduction in the relative risk at 500 g/day of vegetables”

Fruit juice intake was inversely associated with coronary heart disease in the high vs low analysis.

“apples/pears, citrus fruits, fruit juices, green leafy vegetables, beta-carotene-rich fruits and vegetables and vitamin C-rich fruits and vegetables showed inverse associations with coronary heart disease in the high vs low analysis”

For vegetables, the summary relative risk per 200 g/day for coronary heart disease was 0.84 (95% CI 0.79-0.90, I2 = 61%).

“0.84 (95% CI: 0.79–0.90, I2 = 61%) for vegetables”

For fruits and vegetables combined, the summary relative risk per 200 g/day for coronary heart disease was 0.92 (95% CI 0.90-0.94, I2 = 0%, n = 15).

“For fruits and vegetables combined, the summary RR per 200 g/day was 0.92 [95% confidence interval (CI): 0.90–0.94, I2 = 0%, n = 15] for coronary heart disease”

• Also stated in: § Coronary heart disease · plain

  “The summary RR per 200 g/day was 0.92 (95% CI: 0.90–0.94, I2 = 0%) for fruits and vegetables”

Beta-carotene-rich fruit and vegetable intake was inversely associated with coronary heart disease in the high vs low analysis.

“apples/pears, citrus fruits, fruit juices, green leafy vegetables, beta-carotene-rich fruits and vegetables and vitamin C-rich fruits and vegetables showed inverse associations with coronary heart disease in the high vs low analysis”

There was a 20% reduction in the relative risk of stroke at 200-350 g/day of fruits.

“20% reduction in the relative risk at 200–350 g/day of fruits”

Green leafy vegetable intake was inversely associated with coronary heart disease in the high vs low analysis.

“apples/pears, citrus fruits, fruit juices, green leafy vegetables, beta-carotene-rich fruits and vegetables and vitamin C-rich fruits and vegetables showed inverse associations with coronary heart disease in the high vs low analysis”

Citrus fruit intake was inversely associated with coronary heart disease in the high vs low analysis.

“apples/pears, citrus fruits, fruit juices, green leafy vegetables, beta-carotene-rich fruits and vegetables and vitamin C-rich fruits and vegetables showed inverse associations with coronary heart disease in the high vs low analysis”

For fruits and vegetables combined, the summary relative risk per 200 g/day for total cancer was 0.97 (95% CI 0.95-0.99, I2 = 49%, n = 12).

“0.97 (95% CI: 0.95–0.99, I2 = 49%, n = 12) for total cancer”

There was no evidence of a nonlinear association between fruit and vegetable intake and coronary heart disease (P for nonlinearity = 0.30).

“There was no evidence of a nonlinear association for fruits and vegetables, Pnonlinearity = 0.30”

There was a 33% reduction in the relative risk of stroke at intakes of 800 g/day of fruits and vegetables.

“There was a 33% reduction in the relative risk at intakes of 800 g/day of fruits and vegetables”

For fruits and vegetables combined, the summary relative risk per 200 g/day for all-cause mortality was 0.90 (95% CI 0.87-0.93, I2 = 83%, n = 15).

“0.90 (95% CI: 0.87–0.93, I2 = 83%, n = 15) for all-cause mortality”

For fruits, the summary relative risk per 200 g/day for stroke was 0.82 (95% CI 0.74-0.90, I2 = 73%).

“0.82 (95% CI: 0.74–0.90, I2 = 73%) for fruits”

Vitamin C-rich fruit and vegetable intake was inversely associated with coronary heart disease in the high vs low analysis.

“apples/pears, citrus fruits, fruit juices, green leafy vegetables, beta-carotene-rich fruits and vegetables and vitamin C-rich fruits and vegetables showed inverse associations with coronary heart disease in the high vs low analysis”

There was a 24% reduction in the relative risk of coronary heart disease at an intake of 800 g/day of fruits and vegetables.

“there was a 24% reduction in the relative risk at an intake of 800 g/day”

For fruits and vegetables combined, the summary relative risk per 200 g/day for stroke was 0.84 (95% CI 0.76-0.92, I2 = 73%, n = 10).

“For fruits and vegetables combined, the summary RR per 200 g/day was 0.92 [95% confidence interval (CI): 0.90–0.94, I2 = 0%, n = 15] for coronary heart disease, 0.84 (95% CI: 0.76–0.92, I2 = 73%, n = 10) for stroke”

• Also stated in: § Stroke · plain

  “The summary RR per 200 g/day was 0.84 (95% CI: 0.76–0.92, I2 = 73%) for fruits and vegetables”

For fruits and vegetables combined, the summary relative risk per 200 g/day for cardiovascular disease was 0.92 (95% CI 0.90-0.95, I2 = 31%, n = 13).

“0.92 (95% CI: 0.90–0.95, I2 = 31%, n = 13) for cardiovascular disease”

There was evidence of a nonlinear association between fruit and vegetables, fruits, and vegetables, and total stroke (P for nonlinearity < 0.0001 for all).

“There was evidence of a nonlinear association between fruit and vegetables, fruits, and vegetables, and total stroke, Pnonlinearity < 0.0001”

Apples/pears intake was inversely associated with coronary heart disease in the high vs low analysis.

“apples/pears, citrus fruits, fruit juices, green leafy vegetables, beta-carotene-rich fruits and vegetables and vitamin C-rich fruits and vegetables showed inverse associations with coronary heart disease in the high vs low analysis”

For fruits, the summary relative risk per 200 g/day for coronary heart disease was 0.90 (95% CI 0.86-0.94, I2 = 44%).

“0.90 (95% CI: 0.86–0.94, I2 = 44%) for fruits”

For vegetables, the summary relative risk per 200 g/day for stroke was 0.87 (95% CI 0.79-0.96, I2 = 63%).

“0.87 (95% CI: 0.79–0.96, I2 = 63%) for vegetables”

High intake of apples/pears is inversely associated with total stroke risk.

“high intakes of apples/pears, citrus fruits, fruit juice, green leafy vegetables and pickled vegetables were inversely associated with total stroke risk”

For haemorrhagic stroke, the summary relative risk per 200 g/day increase in vegetable intake was 0.76 (95% CI 0.55-1.06, I2 = 42%).

“0.76 (95% CI: 0.55–1.06, I2 = 42%) for vegetables”

For total cancer, most of the reductions in risk occurred at lower levels of intake.

“with most of the reductions in risk at lower levels of intake”

For all-cause mortality, the summary relative risk for fruit and vegetable intake combined was 0.90 (95% CI 0.87-0.93, I2 = 83%).

“The summary RR was 0.90 (95% CI: 0.87–0.93, I2 = 83%) for fruits and vegetables”

For cardiovascular disease, the summary relative risk for fruit intake was 0.87 (95% CI 0.82-0.92, I2 = 79%).

“0.87 (95% CI: 0.82–0.92, I2 = 79%) for fruits”

High intake of fruit juice is inversely associated with total stroke risk.

“high intakes of apples/pears, citrus fruits, fruit juice, green leafy vegetables and pickled vegetables were inversely associated with total stroke risk”

For all-cause mortality, there was a 25% reduction in relative risk at an intake of 600 g/day for vegetables.

“There were 31%, 19% and 25% reductions in the relative risk with intakes of 800 g/day for fruits and vegetables combined, and at 600 g/day for fruits, and for vegetables, respectively.”

For haemorrhagic stroke, the summary relative risk per 200 g/day increase in fruit intake was 0.66 (95% CI 0.50-0.86, I2 = 57%).

“0.66 (95% CI: 0.50–0.86, I2 = 57%) for fruits”

There was evidence of nonlinearity for vegetables and cardiovascular disease, Pnonlinearity = 0.04.

“There was evidence of nonlinearity, Pnonlinearity < 0.0001, for fruits and vegetables (Figure 4b; Supplementary Table 14), and fruits, Pnonlinearity < 0.0001, (Figure 4d; Supplementary Table 15), and for vegetables, Pnonlinearity = 0.04 (Figure 4f; Supplementary Table 15)”

Tomato intake was inversely associated with coronary heart disease in the dose-response analysis.

“tomatoes were inversely associated with coronary heart disease in the dose-response analysis”

Intake of citrus fruits is inversely associated with ischaemic stroke risk.

“For ischaemic stroke26,109–111,121,146,150,162,164 there was evidence that intake of citrus fruits, citrus fruit juices, green leafy vegetables, and vitamin C-rich fruits and vegetables were inversely associated with risk”

For ischaemic stroke, the summary relative risk per 200 g/day increase in vegetable intake was 0.86 (95% CI 0.76-0.97, I2 = 55%).

“0.86 (95% CI: 0.76–0.97, I2 = 55%) for vegetables”

High intake of citrus fruits is inversely associated with total stroke risk.

“high intakes of apples/pears, citrus fruits, fruit juice, green leafy vegetables and pickled vegetables were inversely associated with total stroke risk”

For total cancer, the summary relative risk for fruit intake was 0.96 (95% CI 0.94-0.99, I2 = 52%).

“0.96 (95% CI: 0.94–0.99, I2 = 52%) for fruits”

High versus low intake of tinned fruits is positively associated with cardiovascular disease risk.

“there was evidence that high vs low intake of apples/pears, citrus fruits, carrots and noncruciferous vegetables were inversely associated, and tinned fruits were positively associated with cardiovascular disease risk, and in the nonlinear dose-response analysis there was evidence that cruciferous vegetables, green leafy vegetables, and tomatoes were inversely associated with risk”

High versus low intake of carrots is inversely associated with cardiovascular disease risk.

“there was evidence that high vs low intake of apples/pears, citrus fruits, carrots and noncruciferous vegetables were inversely associated, and tinned fruits were positively associated with cardiovascular disease risk, and in the nonlinear dose-response analysis there was evidence that cruciferous vegetables, green leafy vegetables, and tomatoes were inversely associated with risk”

For vegetables and cardiovascular disease, the association was approximately linear.

“although for vegetables the association was approximately linear”

High intake of green leafy vegetables is inversely associated with total stroke risk.

“high intakes of apples/pears, citrus fruits, fruit juice, green leafy vegetables and pickled vegetables were inversely associated with total stroke risk”

For all-cause mortality, the summary relative risk for vegetable intake was 0.87 (95% CI 0.82-0.92, I2 = 82%).

“0.87 (95% CI: 0.82–0.92, I2 = 82%) for vegetables”

In nonlinear dose-response analysis, cruciferous vegetables are inversely associated with cardiovascular disease risk.

“there was evidence that high vs low intake of apples/pears, citrus fruits, carrots and noncruciferous vegetables were inversely associated, and tinned fruits were positively associated with cardiovascular disease risk, and in the nonlinear dose-response analysis there was evidence that cruciferous vegetables, green leafy vegetables, and tomatoes were inversely associated with risk”

For cardiovascular disease, there was a 28% reduction in relative risk at an intake of 600 g/day for vegetables.

“There were 28%, 27% and 28% reductions in relative risk at intakes of 800 g/day for fruits and vegetables and fruits, and 600 g/day of vegetables, respectively.”

Intake of green leafy vegetables is inversely associated with ischaemic stroke risk.

“For ischaemic stroke26,109–111,121,146,150,162,164 there was evidence that intake of citrus fruits, citrus fruit juices, green leafy vegetables, and vitamin C-rich fruits and vegetables were inversely associated with risk”

For cardiovascular disease, the summary relative risk for fruit and vegetable intake combined was 0.92 (95% CI 0.90-0.95, I2 = 31%).

“The summary RR was 0.92 (95% CI: 0.90–0.95, I2 = 31%) for fruits and vegetables”

Intake of grapes is inversely associated with total stroke risk in the dose-response analysis.

“intake of grapes was also inversely associated with total stroke in the dose-response analysis”

In the analysis of vegetables and cardiovascular disease, there was a stronger association among studies with mortality as the outcome compared with studies with incidence as the outcome, Pheterogeneity = 0.03.

“in the analysis of vegetables and cardiovascular disease there was a stronger association among studies with mortality as the outcome compared with studies with incidence as the outcome, Pheterogeneity = 0.03”

Intake of citrus fruit juices is inversely associated with ischaemic stroke risk.

“For ischaemic stroke26,109–111,121,146,150,162,164 there was evidence that intake of citrus fruits, citrus fruit juices, green leafy vegetables, and vitamin C-rich fruits and vegetables were inversely associated with risk”

In the analysis of fruits and vegetables and all-cause mortality, there was a weaker association among studies that adjusted for red and processed meat intake compared to studies with such adjustment, Pheterogeneity < 0.0001.

“In the analysis of fruits and vegetables and all-cause mortality there was a weaker association among the studies that adjusted for red and processed meat intake compared to studies with such adjustment, Pheterogeneity < 0.0001”

Green-yellow vegetables are significantly inversely associated with total cancer risk.

“there were significant inverse associations between cruciferous vegetables and green-yellow vegetables and total cancer risk”

For cardiovascular disease, the summary relative risk for vegetable intake was 0.90 (95% CI 0.87-0.93, I2 = 12%).

“0.90 (95% CI: 0.87–0.93, I2 = 12%) for vegetables”

For all-cause mortality, there were stronger reductions in risk at lower levels of intake.

“with stronger reductions in risk at lower levels of intake”

For total cancer, the summary relative risk for vegetable intake was 0.96 (95% CI 0.93-0.99, I2 = 55%).

“0.96 (95% CI: 0.93–0.99, I2 = 55%) for vegetables”

In the analysis of fruits and vegetables and cardiovascular disease, there was a weaker association among studies with adjustment for body mass index than among studies without such adjustment, Pheterogeneity = 0.03.

“In the analysis of fruits and vegetables and cardiovascular disease there was a weaker association among studies with adjustment for body mass index (BMI) than among studies without such adustment, Pheterogeneity = 0.03”

For all-cause mortality, the summary relative risk for fruit intake was 0.85 (95% CI 0.80-0.91, I2 = 90%).

“0.85 (95% CI: 0.80–0.91, I2 = 90%) for fruits”

For all-cause mortality, there was a 31% reduction in relative risk at an intake of 800 g/day for fruits and vegetables combined.

“There were 31%, 19% and 25% reductions in the relative risk with intakes of 800 g/day for fruits and vegetables combined, and at 600 g/day for fruits, and for vegetables, respectively.”

In nonlinear dose-response analysis, tomatoes are inversely associated with cardiovascular disease risk.

“there was evidence that high vs low intake of apples/pears, citrus fruits, carrots and noncruciferous vegetables were inversely associated, and tinned fruits were positively associated with cardiovascular disease risk, and in the nonlinear dose-response analysis there was evidence that cruciferous vegetables, green leafy vegetables, and tomatoes were inversely associated with risk”

High versus low intake of noncruciferous vegetables is inversely associated with cardiovascular disease risk.

“there was evidence that high vs low intake of apples/pears, citrus fruits, carrots and noncruciferous vegetables were inversely associated, and tinned fruits were positively associated with cardiovascular disease risk, and in the nonlinear dose-response analysis there was evidence that cruciferous vegetables, green leafy vegetables, and tomatoes were inversely associated with risk”

High versus low intake of apples/pears is inversely associated with cardiovascular disease risk.

“there was evidence that high vs low intake of apples/pears, citrus fruits, carrots and noncruciferous vegetables were inversely associated, and tinned fruits were positively associated with cardiovascular disease risk, and in the nonlinear dose-response analysis there was evidence that cruciferous vegetables, green leafy vegetables, and tomatoes were inversely associated with risk”

For total cancer, there was little evidence of further reductions in risk with higher intakes.

“but there was little evidence of further reductions in risk with higher intakes”

Cruciferous vegetables are significantly inversely associated with total cancer risk.

“there were significant inverse associations between cruciferous vegetables and green-yellow vegetables and total cancer risk”

In nonlinear dose-response analysis, green leafy vegetables are inversely associated with cardiovascular disease risk.

“there was evidence that high vs low intake of apples/pears, citrus fruits, carrots and noncruciferous vegetables were inversely associated, and tinned fruits were positively associated with cardiovascular disease risk, and in the nonlinear dose-response analysis there was evidence that cruciferous vegetables, green leafy vegetables, and tomatoes were inversely associated with risk”

For cardiovascular disease, the inverse associations were steeper at lower levels of intake for fruits and vegetables and fruits.

“with steeper inverse associations at lower levels of intake”

For haemorrhagic stroke, the summary relative risk per 200 g/day increase in fruit and vegetable intake combined was 0.88 (95% CI 0.78-0.99, I2 = 0%).

“0.88 (95% CI: 0.78–0.99, I2 = 0%) for fruits and vegetables combined”

Intake of vitamin C-rich fruits and vegetables is inversely associated with ischaemic stroke risk.

“For ischaemic stroke26,109–111,121,146,150,162,164 there was evidence that intake of citrus fruits, citrus fruit juices, green leafy vegetables, and vitamin C-rich fruits and vegetables were inversely associated with risk”

None of the associations with haemorrhagic stroke were significant.

“none of the associations with haemorrhagic stroke26,109,146,150,164 were significant”

For total cancer, the summary relative risk for fruit and vegetable intake combined was 0.97 (95% CI 0.95-0.99, I2 = 49%).

“The summary RR was 0.97 (95% CI: 0.95–0.99, I2 = 49%) for fruits and vegetables combined”

For cardiovascular disease, there was a 28% reduction in relative risk at an intake of 800 g/day for fruits and vegetables.

“There were 28%, 27% and 28% reductions in relative risk at intakes of 800 g/day for fruits and vegetables and fruits, and 600 g/day of vegetables, respectively.”

There was evidence of nonlinearity for vegetables and all-cause mortality, Pnonlinearity < 0.0001.

“There was evidence of nonlinearity for fruits and vegetables, Pnonlinearity < 0.0001 (Figure 6b; Supplementary Table 18), fruits, Pnonlinearity < 0.0001 (Figure 6d; Supplementary Table 18), and vegetables, Pnonlinearity < 0.0001 (Figure 6f; Supplementary Table 18), respectively”

For all-cause mortality, there was a 19% reduction in relative risk at an intake of 600 g/day for fruits.

“There were 31%, 19% and 25% reductions in the relative risk with intakes of 800 g/day for fruits and vegetables combined, and at 600 g/day for fruits, and for vegetables, respectively.”

For total cancer, there was a 12% reduction in relative risk for an intake of 550-600 g/day for vegetables.

“There were 14%, 8% and 12% reductions in the relative risk for intakes of 550–600 g/day for fruits and vegetables, fruits, and vegetables, respectively”

For total cancer, there was a 14% reduction in relative risk for an intake of 550-600 g/day for fruits and vegetables.

“There were 14%, 8% and 12% reductions in the relative risk for intakes of 550–600 g/day for fruits and vegetables, fruits, and vegetables, respectively”

There was evidence of nonlinearity for fruits and vegetables and cardiovascular disease, Pnonlinearity < 0.0001.

“There was evidence of nonlinearity, Pnonlinearity < 0.0001, for fruits and vegetables (Figure 4b; Supplementary Table 14), and fruits, Pnonlinearity < 0.0001, (Figure 4d; Supplementary Table 15), and for vegetables, Pnonlinearity = 0.04 (Figure 4f; Supplementary Table 15)”

In the analysis of vegetables and all-cause mortality, there was a stronger association among studies without adjustment for smoking than among studies with such adjustment, Pheterogeneity = 0.003.

“in the analysis of vegetables and all-cause mortality there was a stronger association among the studies without adjustment for smoking than among studies with such adjustment, Pheterogeneity = 0.003”

For cardiovascular disease, there was a 27% reduction in relative risk at an intake of 800 g/day for fruits.

“There were 28%, 27% and 28% reductions in relative risk at intakes of 800 g/day for fruits and vegetables and fruits, and 600 g/day of vegetables, respectively.”

There was evidence of nonlinearity for fruits and cardiovascular disease, Pnonlinearity < 0.0001.

“There was evidence of nonlinearity, Pnonlinearity < 0.0001, for fruits and vegetables (Figure 4b; Supplementary Table 14), and fruits, Pnonlinearity < 0.0001, (Figure 4d; Supplementary Table 15), and for vegetables, Pnonlinearity = 0.04 (Figure 4f; Supplementary Table 15)”

There was evidence of nonlinearity for fruits and all-cause mortality, Pnonlinearity < 0.0001.

“There was evidence of nonlinearity for fruits and vegetables, Pnonlinearity < 0.0001 (Figure 6b; Supplementary Table 18), fruits, Pnonlinearity < 0.0001 (Figure 6d; Supplementary Table 18), and vegetables, Pnonlinearity < 0.0001 (Figure 6f; Supplementary Table 18), respectively”

For total cancer, there was an 8% reduction in relative risk for an intake of 550-600 g/day for fruits.

“There were 14%, 8% and 12% reductions in the relative risk for intakes of 550–600 g/day for fruits and vegetables, fruits, and vegetables, respectively”

High versus low intake of citrus fruits is inversely associated with cardiovascular disease risk.

“there was evidence that high vs low intake of apples/pears, citrus fruits, carrots and noncruciferous vegetables were inversely associated, and tinned fruits were positively associated with cardiovascular disease risk, and in the nonlinear dose-response analysis there was evidence that cruciferous vegetables, green leafy vegetables, and tomatoes were inversely associated with risk”

High intake of pickled vegetables is inversely associated with total stroke risk.

“high intakes of apples/pears, citrus fruits, fruit juice, green leafy vegetables and pickled vegetables were inversely associated with total stroke risk”

Globally in 2013, an estimated 5.4 million premature deaths were attributable to a fruit and vegetable intake below 500 g/day.

“Globally an estimated 710 000 coronary heart disease deaths, 1.47 million stroke deaths, 560 000 cancer deaths and 5.4 million premature deaths were attributable to a fruit and vegetable intake below 500 g/day in 2013”

• AssumptionThe authors state this as an assumption: A causal relationship exists between fruit and vegetable intake and coronary heart disease, stroke, cardiovascular disease, total cancer and all-cause mortality.
• AssumptionThe authors state this as an assumption: There is a lack of confounding in the association between fruit and vegetable intake and the outcomes.
• AssumptionThe authors state this as an assumption: The results can be generalized across populations.

In nonlinear models, for an intake of 500 g of fruits and vegetables per day vs 0-40 g/day, the RR of all-cause mortality was reduced by 27%.

“In the nonlinear models, there were 16%, 28%, 22%, 13% and 27% reductions in the RR of coronary heart disease, stroke, cardiovascular disease, total cancer and all-cause mortality, respectively, for an intake of 500 g of fruits and vegetables per day vs 0–40 g/day”

Intake of tinned fruits was associated with increased risk of all-cause mortality.

“In contrast, intake of tinned fruits was associated with increased risk of cardiovascular disease and all-cause mortality.”

For each 200 g/day increment in intake of fruit, vegetables, and fruit and vegetables combined, the RR of coronary heart disease was reduced by 8-16%.

“There was a 8–16% reduction in the RR of coronary heart disease, 13–18% reduction in the RR of stroke, 8–13% reduction in the RR of cardiovascular disease, 3–4% reduction in the RR of total cancer and 10–15% reduction in the RR of all-cause mortality for each 200 g/day increment in intake of fruit, vegetables, and fruit and vegetables combined.”

When using 800 g/day as the optimal intake, an estimated 660,000 cancer deaths were attributable to a fruit and vegetable intake below 800 g/day.

“and this increased to 1.34 million coronary heart disease deaths, 2.68 million stroke deaths, 660 000 cancer deaths and 7.8 million deaths from all causes when using 800 g/day as the optimal intake.”

• AssumptionThe authors state this as an assumption: A causal relationship exists between fruit and vegetable intake and coronary heart disease, stroke, cardiovascular disease, total cancer and all-cause mortality.
• AssumptionThe authors state this as an assumption: There is a lack of confounding in the association between fruit and vegetable intake and the outcomes.
• AssumptionThe authors state this as an assumption: The results can be generalized across populations.

For an intake of 800 g/day vs 0-40 g/day, the RR of cardiovascular disease was reduced by 28%.

“whereas an intake of 800 g/day was associated with 24%, 33%, 28%, 14% and 31% reductions in the RR, respectively.”

When we conducted subgroup analyses to investigate sources of heterogeneity, we found in general little evidence of heterogeneity between most subgroups.

“However, when we conducted subgroup analyses to investigate sources of the heterogeneity, we found in general little evidence of heterogeneity between most subgroups.”

For total cancer the lowest risk was observed at an intake of 600 g/day (7.5 servings/day).

“For total cancer the lowest risk was observed at an intake of 600 g/day (7.5 servings/day)”

There is an inverse association between intake of fruits, vegetables, and fruit and vegetables combined, and the risk of all-cause mortality.

“In conclusion, we found an inverse association between intake of fruits, vegetables, and fruit and vegetables combined, and the risk of coronary heart disease, stroke, cardiovascular disease, total cancer and all-cause mortality.”

For each 200 g/day increment in intake of fruit, vegetables, and fruit and vegetables combined, the RR of all-cause mortality was reduced by 10-15%.

“There was a 8–16% reduction in the RR of coronary heart disease, 13–18% reduction in the RR of stroke, 8–13% reduction in the RR of cardiovascular disease, 3–4% reduction in the RR of total cancer and 10–15% reduction in the RR of all-cause mortality for each 200 g/day increment in intake of fruit, vegetables, and fruit and vegetables combined.”

There was indication of small-study bias in several of the analyses.

“There was indication of small-study bias in several of the analyses, and we may therefore have slightly overestimated some of the associations.”

For each 200 g/day increment in intake of fruit, vegetables, and fruit and vegetables combined, the RR of cardiovascular disease was reduced by 8-13%.

“There was a 8–16% reduction in the RR of coronary heart disease, 13–18% reduction in the RR of stroke, 8–13% reduction in the RR of cardiovascular disease, 3–4% reduction in the RR of total cancer and 10–15% reduction in the RR of all-cause mortality for each 200 g/day increment in intake of fruit, vegetables, and fruit and vegetables combined.”

For fruits and vegetables combined, the lowest risk for coronary heart disease, stroke, cardiovascular disease and all-cause mortality was observed at 800 g/day (10 servings/day).

“whereas for coronary heart disease, stroke, cardiovascular disease and all-cause mortality the lowest risk was observed at 800 g/day (10 servings/day), which was at the high end of the range of intake across studies.”

For an intake of 800 g/day vs 0-40 g/day, the RR of total cancer was reduced by 14%.

“whereas an intake of 800 g/day was associated with 24%, 33%, 28%, 14% and 31% reductions in the RR, respectively.”

When using 800 g/day as the optimal intake, an estimated 1.34 million coronary heart disease deaths were attributable to a fruit and vegetable intake below 800 g/day.

“and this increased to 1.34 million coronary heart disease deaths, 2.68 million stroke deaths, 660 000 cancer deaths and 7.8 million deaths from all causes when using 800 g/day as the optimal intake.”

• AssumptionThe authors state this as an assumption: A causal relationship exists between fruit and vegetable intake and coronary heart disease, stroke, cardiovascular disease, total cancer and all-cause mortality.
• AssumptionThe authors state this as an assumption: There is a lack of confounding in the association between fruit and vegetable intake and the outcomes.
• AssumptionThe authors state this as an assumption: The results can be generalized across populations.

Globally in 2013, an estimated 560,000 cancer deaths were attributable to a fruit and vegetable intake below 500 g/day.

“Globally an estimated 710 000 coronary heart disease deaths, 1.47 million stroke deaths, 560 000 cancer deaths and 5.4 million premature deaths were attributable to a fruit and vegetable intake below 500 g/day in 2013”

• AssumptionThe authors state this as an assumption: A causal relationship exists between fruit and vegetable intake and coronary heart disease, stroke, cardiovascular disease, total cancer and all-cause mortality.
• AssumptionThe authors state this as an assumption: There is a lack of confounding in the association between fruit and vegetable intake and the outcomes.
• AssumptionThe authors state this as an assumption: The results can be generalized across populations.

For each 200 g/day increment in intake of fruit, vegetables, and fruit and vegetables combined, the RR of stroke was reduced by 13-18%.

“There was a 8–16% reduction in the RR of coronary heart disease, 13–18% reduction in the RR of stroke, 8–13% reduction in the RR of cardiovascular disease, 3–4% reduction in the RR of total cancer and 10–15% reduction in the RR of all-cause mortality for each 200 g/day increment in intake of fruit, vegetables, and fruit and vegetables combined.”

Fruit and vegetable intake was only weakly associated with overall cancer risk, particularly cancer incidence.

“Fruit and vegetable intake was only weakly associated with overall cancer risk, particularly cancer incidence”

Globally in 2013, an estimated 710,000 coronary heart disease deaths were attributable to a fruit and vegetable intake below 500 g/day.

“Globally an estimated 710 000 coronary heart disease deaths, 1.47 million stroke deaths, 560 000 cancer deaths and 5.4 million premature deaths were attributable to a fruit and vegetable intake below 500 g/day in 2013”

• AssumptionThe authors state this as an assumption: A causal relationship exists between fruit and vegetable intake and coronary heart disease, stroke, cardiovascular disease, total cancer and all-cause mortality.
• AssumptionThe authors state this as an assumption: There is a lack of confounding in the association between fruit and vegetable intake and the outcomes.
• AssumptionThe authors state this as an assumption: The results can be generalized across populations.

When using 800 g/day as the optimal intake, an estimated 2.68 million stroke deaths were attributable to a fruit and vegetable intake below 800 g/day.

“and this increased to 1.34 million coronary heart disease deaths, 2.68 million stroke deaths, 660 000 cancer deaths and 7.8 million deaths from all causes when using 800 g/day as the optimal intake.”

• AssumptionThe authors state this as an assumption: A causal relationship exists between fruit and vegetable intake and coronary heart disease, stroke, cardiovascular disease, total cancer and all-cause mortality.
• AssumptionThe authors state this as an assumption: There is a lack of confounding in the association between fruit and vegetable intake and the outcomes.
• AssumptionThe authors state this as an assumption: The results can be generalized across populations.

Using total cardiovascular disease instead of coronary heart disease and stroke mortality, an estimated 1.25 million cardiovascular disease deaths were attributable to a fruit and vegetable intake below 500 g/day.

“Alternatively, using total cardiovascular disease instead of coronary heart disease and stroke mortality, an estimated 1.25 and 2.26 million cardiovascular disease deaths were attributable to a fruit and vegetable intake below 500 and 800 g/day, respectively.”

• AssumptionThe authors state this as an assumption: A causal relationship exists between fruit and vegetable intake and coronary heart disease, stroke, cardiovascular disease, total cancer and all-cause mortality.
• AssumptionThe authors state this as an assumption: There is a lack of confounding in the association between fruit and vegetable intake and the outcomes.
• AssumptionThe authors state this as an assumption: The results can be generalized across populations.

In nonlinear models, for an intake of 500 g of fruits and vegetables per day vs 0-40 g/day, the RR of cardiovascular disease was reduced by 22%.

“In the nonlinear models, there were 16%, 28%, 22%, 13% and 27% reductions in the RR of coronary heart disease, stroke, cardiovascular disease, total cancer and all-cause mortality, respectively, for an intake of 500 g of fruits and vegetables per day vs 0–40 g/day”

There is an inverse association between intake of fruits, vegetables, and fruit and vegetables combined, and the risk of coronary heart disease.

“In conclusion, we found an inverse association between intake of fruits, vegetables, and fruit and vegetables combined, and the risk of coronary heart disease, stroke, cardiovascular disease, total cancer and all-cause mortality.”

There is an inverse association between intake of fruits, vegetables, and fruit and vegetables combined, and the risk of cardiovascular disease.

“In conclusion, we found an inverse association between intake of fruits, vegetables, and fruit and vegetables combined, and the risk of coronary heart disease, stroke, cardiovascular disease, total cancer and all-cause mortality.”

For an intake of 800 g/day vs 0-40 g/day, the RR of coronary heart disease was reduced by 24%.

“whereas an intake of 800 g/day was associated with 24%, 33%, 28%, 14% and 31% reductions in the RR, respectively.”

We found significant inverse associations with overall cancer risk.

“In addition, we found significant inverse associations with overall cancer risk”

In nonlinear models, for an intake of 500 g of fruits and vegetables per day vs 0-40 g/day, the RR of stroke was reduced by 28%.

“In the nonlinear models, there were 16%, 28%, 22%, 13% and 27% reductions in the RR of coronary heart disease, stroke, cardiovascular disease, total cancer and all-cause mortality, respectively, for an intake of 500 g of fruits and vegetables per day vs 0–40 g/day”

Globally in 2013, an estimated 1.47 million stroke deaths were attributable to a fruit and vegetable intake below 500 g/day.

“Globally an estimated 710 000 coronary heart disease deaths, 1.47 million stroke deaths, 560 000 cancer deaths and 5.4 million premature deaths were attributable to a fruit and vegetable intake below 500 g/day in 2013”

• AssumptionThe authors state this as an assumption: A causal relationship exists between fruit and vegetable intake and coronary heart disease, stroke, cardiovascular disease, total cancer and all-cause mortality.
• AssumptionThe authors state this as an assumption: There is a lack of confounding in the association between fruit and vegetable intake and the outcomes.
• AssumptionThe authors state this as an assumption: The results can be generalized across populations.

In nonlinear models, for an intake of 500 g of fruits and vegetables per day vs 0-40 g/day, the RR of coronary heart disease was reduced by 16%.

“In the nonlinear models, there were 16%, 28%, 22%, 13% and 27% reductions in the RR of coronary heart disease, stroke, cardiovascular disease, total cancer and all-cause mortality, respectively, for an intake of 500 g of fruits and vegetables per day vs 0–40 g/day”

Several individual types of fruits and vegetables were inversely associated with total cancer (cruciferous vegetables and green-yellow vegetables).

“total cancer (cruciferous vegetables and green-yellow vegetables)”

Several individual types of fruits and vegetables were inversely associated with all-cause mortality (apples/pears, berries, citrus fruits, cooked vegetables, cruciferous vegetables, potatoes, and green leafy vegetables/salads).

“all-cause mortality (apples/pears, berries, citrus fruits, cooked vegetables, cruciferous vegetables, potatoes, and green leafy vegetables/salads)”

For an intake of 800 g/day vs 0-40 g/day, the RR of stroke was reduced by 33%.

“whereas an intake of 800 g/day was associated with 24%, 33%, 28%, 14% and 31% reductions in the RR, respectively.”

When using 800 g/day as the optimal intake, an estimated 7.8 million deaths from all causes were attributable to a fruit and vegetable intake below 800 g/day.

“and this increased to 1.34 million coronary heart disease deaths, 2.68 million stroke deaths, 660 000 cancer deaths and 7.8 million deaths from all causes when using 800 g/day as the optimal intake.”

• AssumptionThe authors state this as an assumption: A causal relationship exists between fruit and vegetable intake and coronary heart disease, stroke, cardiovascular disease, total cancer and all-cause mortality.
• AssumptionThe authors state this as an assumption: There is a lack of confounding in the association between fruit and vegetable intake and the outcomes.
• AssumptionThe authors state this as an assumption: The results can be generalized across populations.

In nonlinear models, for an intake of 500 g of fruits and vegetables per day vs 0-40 g/day, the RR of total cancer was reduced by 13%.

“In the nonlinear models, there were 16%, 28%, 22%, 13% and 27% reductions in the RR of coronary heart disease, stroke, cardiovascular disease, total cancer and all-cause mortality, respectively, for an intake of 500 g of fruits and vegetables per day vs 0–40 g/day”

For an intake of 800 g/day vs 0-40 g/day, the RR of all-cause mortality was reduced by 31%.

“whereas an intake of 800 g/day was associated with 24%, 33%, 28%, 14% and 31% reductions in the RR, respectively.”

Using total cardiovascular disease instead of coronary heart disease and stroke mortality, an estimated 2.26 million cardiovascular disease deaths were attributable to a fruit and vegetable intake below 800 g/day.

“Alternatively, using total cardiovascular disease instead of coronary heart disease and stroke mortality, an estimated 1.25 and 2.26 million cardiovascular disease deaths were attributable to a fruit and vegetable intake below 500 and 800 g/day, respectively.”

• AssumptionThe authors state this as an assumption: A causal relationship exists between fruit and vegetable intake and coronary heart disease, stroke, cardiovascular disease, total cancer and all-cause mortality.
• AssumptionThe authors state this as an assumption: There is a lack of confounding in the association between fruit and vegetable intake and the outcomes.
• AssumptionThe authors state this as an assumption: The results can be generalized across populations.

We did not find significant heterogeneity in the association between fruits and vegetables and the outcomes considered by region for the geographical locations for which data were available (North America, Europe, Australia and Asia).

“However, we did not find significant heterogeneity in the association between fruits and vegetables and the outcomes considered by region for the geographical locations for which data were available (North America, Europe, Australia and Asia).”

In most of the analyses the reduction in risk was steeper at the lower than at the higher range of fruit and vegetable intake.

“and in most of the analyses the reduction in risk was steeper at the lower than at the higher range of fruit and vegetable intake.”

There was evidence of nonlinearity in all analyses of fruits and vegetables combined, apart from one.

“There was evidence of nonlinearity in all analyses of fruits and vegetables combined, apart from one”

Several individual types of fruits and vegetables were inversely associated with coronary heart disease, stroke or cardiovascular disease (apples/pears, citrus fruits, cruciferous vegetables, green leafy vegetables, tomatoes and beta-carotene-rich and vitamin C-rich fruit and vegetables).

“We found that several individual types of fruits and vegetables were inversely associated with coronary heart disease, stroke or cardiovascular disease (apples/pears, citrus fruits, cruciferous vegetables, green leafy vegetables, tomatoes and beta-carotene-rich and vitamin C-rich fruit and vegetables)”

There is an inverse association between intake of fruits, vegetables, and fruit and vegetables combined, and the risk of total cancer.

“In conclusion, we found an inverse association between intake of fruits, vegetables, and fruit and vegetables combined, and the risk of coronary heart disease, stroke, cardiovascular disease, total cancer and all-cause mortality.”

For each 200 g/day increment in intake of fruit, vegetables, and fruit and vegetables combined, the RR of total cancer was reduced by 3-4%.

“There was a 8–16% reduction in the RR of coronary heart disease, 13–18% reduction in the RR of stroke, 8–13% reduction in the RR of cardiovascular disease, 3–4% reduction in the RR of total cancer and 10–15% reduction in the RR of all-cause mortality for each 200 g/day increment in intake of fruit, vegetables, and fruit and vegetables combined.”

Intake of tinned fruits was associated with increased risk of cardiovascular disease.

“In contrast, intake of tinned fruits was associated with increased risk of cardiovascular disease and all-cause mortality.”

There is an inverse association between intake of fruits, vegetables, and fruit and vegetables combined, and the risk of stroke.

“In conclusion, we found an inverse association between intake of fruits, vegetables, and fruit and vegetables combined, and the risk of coronary heart disease, stroke, cardiovascular disease, total cancer and all-cause mortality.”

There was evidence of publication bias in some analyses for coronary heart disease, stroke, cardiovascular disease and all-cause mortality.

“There was evidence of publication bias in some of the analyses for coronary heart disease, stroke, cardiovascular disease and all-cause mortality”

Under the assumption that the observed associations are causal, the estimated number of premature deaths attributable to a fruit and vegetable intake below 800 g/day in 2013 was 7,800,000 for all-cause mortality.

“Under the assumption that the observed associations are causal we estimated that the number of premature deaths attributable to a fruit and vegetable intake below 800 g/day in 2013 was 1 340 000 for coronary heart disease, 2 680 000 for stroke, 2 270 000 for cardiovascular disease, 660 000 for cancer and 7 800 000 for all-cause mortality”

• AssumptionThe authors state this as an assumption: The observed associations between fruit and vegetable intake and the health outcomes are causal.

Study quality was in general high, as the vast majority of studies were in the group with 7-9 stars.

“The study quality was in general high as the vast majority of studies were in the group with 7–9 stars”

The results persisted in sensitivity analyses excluding one study at a time from each analysis.

“The results persisted in sensitivity analyses excluding one study at a time from each analysis”

Under the assumption that the observed associations are causal, the estimated number of premature deaths attributable to a fruit and vegetable intake below 800 g/day in 2013 was 1,340,000 for coronary heart disease.

“Under the assumption that the observed associations are causal we estimated that the number of premature deaths attributable to a fruit and vegetable intake below 800 g/day in 2013 was 1 340 000 for coronary heart disease, 2 680 000 for stroke, 2 270 000 for cardiovascular disease, 660 000 for cancer and 7 800 000 for all-cause mortality”

• AssumptionThe authors state this as an assumption: The observed associations between fruit and vegetable intake and the health outcomes are causal.

Few studies were included in the nonlinear dose-response analyses of fruit and vegetable subtypes and cardiovascular disease.

“although few studies were included in these analyses”

Under the assumption that the observed associations are causal, the estimated number of premature deaths attributable to a fruit and vegetable intake below 800 g/day in 2013 was 660,000 for cancer.

“Under the assumption that the observed associations are causal we estimated that the number of premature deaths attributable to a fruit and vegetable intake below 800 g/day in 2013 was 1 340 000 for coronary heart disease, 2 680 000 for stroke, 2 270 000 for cardiovascular disease, 660 000 for cancer and 7 800 000 for all-cause mortality”

• AssumptionThe authors state this as an assumption: The observed associations between fruit and vegetable intake and the health outcomes are causal.

Under the assumption that the observed associations are causal, the estimated number of premature deaths attributable to a fruit and vegetable intake below 800 g/day in 2013 was 2,680,000 for stroke.

“Under the assumption that the observed associations are causal we estimated that the number of premature deaths attributable to a fruit and vegetable intake below 800 g/day in 2013 was 1 340 000 for coronary heart disease, 2 680 000 for stroke, 2 270 000 for cardiovascular disease, 660 000 for cancer and 7 800 000 for all-cause mortality”

• AssumptionThe authors state this as an assumption: The observed associations between fruit and vegetable intake and the health outcomes are causal.

Under the assumption that the observed associations are causal, the estimated number of premature deaths attributable to a fruit and vegetable intake below 800 g/day in 2013 was 2,270,000 for cardiovascular disease.

“Under the assumption that the observed associations are causal we estimated that the number of premature deaths attributable to a fruit and vegetable intake below 800 g/day in 2013 was 1 340 000 for coronary heart disease, 2 680 000 for stroke, 2 270 000 for cardiovascular disease, 660 000 for cancer and 7 800 000 for all-cause mortality”

• AssumptionThe authors state this as an assumption: The observed associations between fruit and vegetable intake and the health outcomes are causal.

Using 500 g/day as a reference category, the estimated number of premature deaths was 710,000 for coronary heart disease.

“We repeated these calculations using 500 g/day as a reference category and arrived at 710 000 coronary heart disease deaths, 1 470 000 stroke deaths, 1 260 000 cardiovascular disease deaths, 560 000 cancer deaths and 5 400 000 all-cause deaths”

• AssumptionThe authors state this as an assumption: The observed associations between fruit and vegetable intake and the health outcomes are causal.

The findings were robust in comprehensive subgroup and sensitivity analyses.

“the robustness of the findings in comprehensive subgroup and sensitivity analyses”

The results from existing cohort studies on all-cause mortality may not be generalizable to sub-Saharan Africa.

“Because the distributions of causes of death differ substantially in sub-Saharan Africa compared with other regions, the results from existing cohort studies on all-cause mortality may not be generalizable to this region.”

We may have slightly overestimated some of the associations due to small-study bias.

“There was indication of small-study bias in several of the analyses, and we may therefore have slightly overestimated some of the associations.”

In the China Kadoorie Cohort Study the HR of cardiovascular death with one daily portion of fresh fruit intake was 0.77 (95% CI: 0.72-0.83) before and 0.63 (95% CI: 0.56-0.72) after correction for regression dilution.

“In the China Kadoorie Cohort Study the HR of cardiovascular death with one daily portion of fresh fruit intake was 0.77 (95% CI: 0.72–0.83) before and 0.63 (95% CI: 0.56–0.72) after correction for regression dilution.”

• cites [63] Du, 2016, Fresh Fruit consumption and major cardiovascular disease in China, N Engl J Med sourceNot checked yet

  Not checked in the free run.

In a sensitivity analysis counting only cause-specific deaths for sub-Saharan Africa, the estimated number of premature deaths globally was 5,240,000 for an intake of 500 g/day and 7,630,000 for an intake of 800 g/day.

“In a sensitivity analysis, we only counted the cause-specific deaths [from coronary heart disease, stroke and total cancer] for sub-Saharan Africa, and arrived at 5 240 000 and 7 630 000 premature deaths globally for an intake of 500 and 800 g/day, respectively.”

• AssumptionThe authors state this as an assumption: The observed associations between fruit and vegetable intake and the health outcomes are causal.

Using 500 g/day as a reference category, the estimated number of premature deaths was 1,470,000 for stroke.

“We repeated these calculations using 500 g/day as a reference category and arrived at 710 000 coronary heart disease deaths, 1 470 000 stroke deaths, 1 260 000 cardiovascular disease deaths, 560 000 cancer deaths and 5 400 000 all-cause deaths”

• AssumptionThe authors state this as an assumption: The observed associations between fruit and vegetable intake and the health outcomes are causal.

Using 500 g/day as a reference category, the estimated number of premature deaths was 5,400,000 for all-cause mortality.

“We repeated these calculations using 500 g/day as a reference category and arrived at 710 000 coronary heart disease deaths, 1 470 000 stroke deaths, 1 260 000 cardiovascular disease deaths, 560 000 cancer deaths and 5 400 000 all-cause deaths”

• AssumptionThe authors state this as an assumption: The observed associations between fruit and vegetable intake and the health outcomes are causal.

The heterogeneity appeared to be driven by differences in the size of the association more than by variation in the presence or absence of an association.

“The heterogeneity appeared to be driven by differences in the size of the association more than by variation in the presence or absence of an association, as most of the studies found inverse associations.”

Using 500 g/day as a reference category, the estimated number of premature deaths was 560,000 for cancer.

“We repeated these calculations using 500 g/day as a reference category and arrived at 710 000 coronary heart disease deaths, 1 470 000 stroke deaths, 1 260 000 cardiovascular disease deaths, 560 000 cancer deaths and 5 400 000 all-cause deaths”

• AssumptionThe authors state this as an assumption: The observed associations between fruit and vegetable intake and the health outcomes are causal.

Using 500 g/day as a reference category, the estimated number of premature deaths was 1,260,000 for cardiovascular disease.

“We repeated these calculations using 500 g/day as a reference category and arrived at 710 000 coronary heart disease deaths, 1 470 000 stroke deaths, 1 260 000 cardiovascular disease deaths, 560 000 cancer deaths and 5 400 000 all-cause deaths”

• AssumptionThe authors state this as an assumption: The observed associations between fruit and vegetable intake and the health outcomes are causal.

It seems less likely that residual confounding could entirely explain the observed associations.

“Thus although we cannot entirely rule out the possibility that residual confounding could partly explain the associations, it seems less likely that it could entirely explain the observed associations.”