An Evidence-based Approach to Phytochemicals and Other Dietary Factors

1 Fruits and Vegetables

Despite all of the controversy surrounding the optimal components of a healthy diet, there is little disagreement among scientists regarding the importance of fruits and vegetables. The results of numerous epidemiological studies and recent clinical trials provide consistent evidence that diets rich in fruits and vegetables can reduce the risk of chronic disease.1 On the other hand, evidence that very high doses of individual micronutrients or phytochemicals found in fruits and vegetables can do the same is inconsistent and relatively weak. Fruits and vegetables contain thousands of biologically active phytochemicals that are likely to interact in several ways to prevent disease and promote health.² Fruits and vegetables are rich in antioxidants, which help protect the body from oxidative damage induced by pro-oxidants. The best way to take advantage of these complex interactions is to eat a variety of fruits and vegetables.

Dietary patterns characterized by relatively high intakes of fruits and vegetables are consistently associated with significant reductions in the risk of coronary heart disease (CHD) and stroke. A meta-analysis that combined the results of 11 prospective cohort studies found that people in the 90th percentile of fruit and vegetable intake (approx. five servings per day or more) had a risk of myocardial infarction (MI) that was around 15% lower than for those in the 10th percentile of intake.3 Among more than 126 000 men and women participating in the Health Professionals’ Follow-up Study and the Nurses’ Health Study, those who consumed eight or more servings of fruits and vegetables daily had a risk of developing CHD over the next 8–14 years that was 20% lower than those who consumed less than three servings daily.⁴ In the same cohort, the risk of ischemic stroke (stroke caused by a reduction in blood flow to part of the brain) was 30% lower in those who consumed at least five servings of fruits and vegetables daily than in those who consumed less than three servings daily.⁵ Based on the results of the Health Professionals’ Follow-up Study and the Nurses’ Health Study (NHS), eating one extra serving of fruits or vegetables daily would decrease one's risk of CHD by approximately 4% and decrease the risk of ischemic stroke by 6%. In a meta-analysis designed to estimate the global burden of disease attributable to low fruit and vegetable consumption, epidemiologists concluded that increasing individual fruit and vegetable consumption (excluding potatoes) up to 600 g/day (approx. seven servings per day) could decrease the risk of CHD by 31% and the risk of ischemic stroke by 19%.¹ Three recent meta-analyses have examined fruit and vegetable consumption and risk of CHD or stroke. In a meta-analysis that included nine cohort studies, an additional daily serving of fruit and vegetables was associated with a 4% decreased risk for CHD.⁶ Another meta-analysis, which examined 12 separate studies, found that individuals who consumed more than five daily servings of fruit and vegetables experienced a 17% reduction in risk of CHD compared with those who consumed less than three servings daily.⁷ In a meta-analysis of eight studies examining fruit and vegetable in-take, individuals who consumed three to five daily servings or more than five daily servings had an 11% or 26% reduction in risk of stroke, respectively, when compared with those who consumed fewer than three servings daily.⁸

High blood pressure (hypertension) increases the risk of heart disease and stroke.⁹ Adding more fruits and vegetables to a sensible diet is one potential way to lower blood pressure. In the Dietary Approaches to Stop Hypertension (DASH) study, 459 people with and without high blood pressure were randomly assigned to one of three diets: (1) a typical American diet that provided approximately three servings per day of fruits and vegetables and one serving per day of a lowfat dairy product, (2) a fruit and vegetable diet that provided eight servings per day of fruits and vegetables and one serving per day of a low-fat dairy product, or (3) a combination diet (now called the DASH diet) that provided nine servings per day of fruits and vegetables and three servings per day of low-fat dairy products.10 After 8 weeks, the blood pressure of those on the fruit and vegetable diet (eight servings per day) was significantly lower than those on the typical American diet, while the blood pressure of those on the combination (DASH) diet (nine servings per day of fruits and vegetables) was lower still.

Several compounds may contribute to the cardioprotective effects of fruits and vegetables, including vitamin C, folate, potassium, fiber, and various phytochemicals.¹¹ However, supplementation of individual micronutrients or phytochemicals has not generally resulted in significantly decreased incidence of cardiovascular events in randomized controlled trials. Thus, in the case of fruits and vegetables, the “benefit of the whole may be greater than the sum of its parts.”

Type 2 Diabetes Mellitus

In addition to other complications, type 2 diabetes mellitus (DM) is associated with increased risk of cardiovascular disease—the leading cause of death in type 2 diabetes.12 Although the evidence for a beneficial effect of a diet rich in fruits and vegetables on diabetes is not as consistent as it is for heart disease, the results of a small number of studies suggest that higher intakes of fruits and vegetables are associated with improved blood glucose control and lower risk of developing type 2 DM. In a cohort of almost 10 000 adults in the United States, the risk of developing type 2 DM over the next 20 years was around 20% lower in those who reported consuming at least five daily servings of fruits and vegetables compared with those who reported consuming none.¹³ In another prospective cohort study that followed more than 40 000 US women for an average of 9 years, fruit and vegetable intake was not associated with the risk of developing type 2 DM in the entire cohort, but higher intakes of green leafy and yellow vegetables were associated with significant reductions in the risk of type 2 DM in overweight women.¹⁴ Higher fruit and vegetable intakes were weakly associated with a reduced risk of diabetes in a cohort of more than 20 000 individuals followed for 12 years.¹⁵ In a cohort of 71 346 women participating in the NHS, total fruit and vegetable intake was not associated with risk for diabetes, although further analysis revealed that intake of fruit or green leafy vegetables was individually associated with a modest reduction in risk of diabetes.¹⁶ A systematic review and meta-analysis of five cohort studies found that fruit and vegetable intake was not associated with type 2 diabetes.¹⁷ However, in a cross-sectional study of more than 6000 adults in the United Kingdom who did not have diabetes, those with higher fruit and vegetable intakes had significantly lower levels of glycosylated hemoglobin (HbA_1c), a measure of long-term blood glucose control.¹⁸ Possible compounds in fruits and vegetables that may enhance glucose control include fiber and magnesium.

Cancer

The results of numerous case–control studies indicate that eating a diet rich in fruits and vegetables decreases the risk of developing several different types of cancer, particularly cancers of the digestive tract (oropharynx, esophagus, stomach, colon, and rectum) and lung.19–21 The results of some of these studies were the foundation for the National Cancer Institute's “5 A Day” program, which was aimed at increasing the fruit and vegetable consumption of the American public to a minimum of five servings daily. The current US government campaign “Fruits & Veggies More Matters” has replaced the “5 A Day” program. In contrast to the results of case–control studies, many recent prospective cohort studies have found little or no association between total fruit and vegetable intake and the risk of various cancers.^22–44 There are several possible explanations for this discrepancy. Case–control studies, in which the past diets of people diagnosed with a particular type of cancer are compared with the diets of people without cancer, are more susceptible to bias in the selection of participants and dietary recall than prospective cohort studies, which collect information on the diets of large cohorts of healthy people and follow the development of disease in the cohort over time.⁴⁵ Although prospective cohort studies provide weak support for an association between total fruit and vegetable consumption and cancer risk, they provide some evidence that high intakes of certain classes of fruits or vegetables are associated with reduced risk of individual cancers. Higher intakes of fruits have been associated with modest but significant reductions in lung cancer risk in a pooled analysis of eight prospective cohort studies,28 and with reductions in risk of bladder cancer in some studies.⁴⁶ In men, higher intakes of cruciferous vegetables have been associated with significant reductions in the risk of bladder cancer,⁴⁷ as well as prostate cancer,⁴⁸ and higher intakes of tomato products have been linked with significant reductions in the risk of prostate cancer.⁴⁹

Osteoporosis

Several cross-sectional studies have reported that higher intakes of fruits and vegetables are associated with significantly higher bone mineral density (BMD) and lower levels of bone resorption (loss) in men and women.50–53 In a study that followed BMD over 4 years, higher fruit and vegetable intakes were associated with significantly less decline in BMD at the hip in elderly men but not elderly women.⁵⁰ Fruits and vegetables are rich in precursors to bicarbonate ions, which serve to buffer acids in the body. When the quantity of bicarbonate ions is insufficient to maintain normal pH, the body is capable of mobilizing alkaline calcium salts from bone to neutralize acids consumed in the diet and generated by metabolism.⁵⁴ Increased consumption of fruits and vegetables reduces the net acid content of the diet and may preserve calcium in bones, which might otherwise be mobilized to maintain normal pH. However, the results of a recent placebo-controlled trial in 276 postmenopausal women suggest that supplementing the diet with alkali, either through supplemental potassium citrate or an additional 300 g/day of fruits and vegetables, did not increase BMD or blunt the age-associated bone loss over a 2-year period.⁵⁵ Results from the DASH study support a beneficial link between fruit and vegetable intake and bone health. In addition to decreasing blood pressure, increasing fruit and vegetable intake from approximately three to nine servings daily decreased urinary calcium loss by almost 50 mg/day¹⁰ and lowered biochemical markers of bone turnover, particularly bone resorption, including serum levels of C-terminal telopeptide of type 1 collagen.⁵⁶ Taken together, the results of epidemiological studies and controlled clinical trials suggest that a diet rich in fruits and vegetables can help prevent bone loss, although the specific mechanisms are not known with certainty.

Age-Related Eye Diseases

Cataracts

Cataracts are thought to be caused by oxidative damage to proteins in the eye's lens, induced by long-term exposure to ultraviolet light. The resulting cloudiness and discoloration of the lens leads to vision loss that becomes more severe with age. The results of several large prospective cohort studies suggest that diets rich in fruits and vegetables, especially fruits and vegetables rich in carotenoid and vitamin C, are associated with decreased incidence and severity of cataracts.57–60 In a study of male US health professionals, high intakes of both broccoli and spinach were associated with fewer cataract extractions.⁵⁷

Macular Degeneration

Degeneration of the macula, the center of the retina, is the leading cause of blindness in people over the age of 65 years in the United States.⁶¹ Lutein and zeaxanthin are carotenoids that are found in relatively high concentrations in the retina; these carotenoids may play a role in preventing damage to the retina caused by light or oxidants.⁶² In two case–control studies, high in-takes of carotenoid-rich vegetables, especially those rich in lutein and zeaxanthin, such as dark green, leafy vegetables, were associated with a significantly lower risk of developing age-related macular degeneration (AMD).^63,64 In a prospective cohort study of more than 118 000 men and women, those who consumed three or more servings of fruits daily had a 36% lower risk of developing AMD over the next 12–18 years than those who consumed fewer than 1.5 servings.⁶⁵ Interestingly, vegetable intake was not associated with the risk of macular degeneration in this cohort. In a more recent study, combined lutein and zeaxanthin intake was not associated with prevalence of intermediate AMD in a cohort of women aged 50–79 years.⁶⁶ However, further analysis of the data revealed that women younger than 75 years with stable intakes of lutein and zeaxanthin had a 43% lower risk of developing intermediate AMD.⁶⁶

Table 1.1 Examples of one serving of fruits or vegetables

Fruit or Vegetable	Amount in One Serving
Fruit or vegetable juice	¾ cup (6 fl oz)
Apple	1 medium
Orange	1 medium
Banana	1 small
Salad greens, raw	1 cup
Chopped fruit or vegetables	½ cup
Cooked vegetables	½ cup
Cooked beans, peas, or lentils	½ cup
Dried fruit	¼ cup

Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a term that includes emphysema and chronic bronchitis, two chronic lung diseases that are characterized by airway obstruction. Although smoking is by far the most important risk factor for COPD, the results of several epidemiological studies suggest beneficial associations between vegetable and, more strongly, fruit intakes and COPD risk.67 The results of several epidemiological studies in Europe indicate that higher fruit intakes, especially apple intakes, are associated with higher forced expiratory volume (FEV₁) values, indicative of better lung function.^68–70 In a study of 2500 middle-aged Welsh men, those who ate at least five apples weekly had a significantly slower decline in lung function than those who did not eat apples over a 5-year period.⁶⁹ In a study of 2917 European men followed over 20 years, each 100 g (3.5 oz) increase in daily fruit consumption was associated with a 24% decrease in the risk of death from COPD.⁷¹ The reasons for the beneficial association between fruit intake and lung health are not yet known. Because oxidative stress is thought to play a role in the etiology of chronic obstructive lung disease, scientists are currently investigating the possibility that antioxidants and phytochemicals found in fruits, such as vitamin C or flavonoids, could play a protective role. Higher fruit and vegetable intake was inversely associated with risk of COPD in a small case–control study of male cigarette smokers,⁷² providing support for the antioxidant hypothesis. Interestingly, when compared with a Western dietary pattern (refined grains, cured and red meats, French fries, and desserts), a prudent dietary pattern that emphasized fruits, vegetables, fish, and whole grains was associated with a 25%–50% reduction in COPD risk in large cohorts of men⁷³ and women.⁷⁴

Neurodegenerative Disease

Although it is not yet clear whether a diet rich in fruits and vegetables will decrease the risk of neurodegenerative diseases like Alzheimer disease and Parkinson disease in humans, studies in animal models of these diseases suggest that diets rich in fruits like blueberries 75 or tomatoes may be protective.⁷⁶ Interestingly, a prospective study that followed 1836 older Japanese Americans for an average of 6.3 years found that regular consumption of fruit and vegetable juices was associated with a decreased risk of developing Alzheimer disease.⁷⁷ More studies are needed to determine whether fruit and vegetable consumption is protective against neurodegenerative diseases.

Intake Recommendations

Many agencies within the US government, including the Centers for Disease Control and Prevention, recommend eating a variety of fruits and vegetables daily; the recommended serving number depends on age, sex, and activity level.78 Table 1.1 provides some examples of a single serving of fruits or vegetables. Consumption of a variety of different fruits and vegetables is recommended, including dark green, red, orange, yellow, blue, and purple fruits and vegetables, as well as legumes (peas and beans), onions, and garlic. Moreover, certain groups of fruits and vegetables, such as cruciferous vegetables, may provide specific health benefits (see Chapter 2). Additionally, fiber-rich, whole fruits are recommended over high-sugar fruit juices.

Summary

• Dietary patterns characterized by high intakes of fruits and vegetables are consistently associated with significant reductions in cardiovascular disease risk.

• Although prospective cohort studies provide weak support for an association between total fruit and vegetable consumption and cancer risk, they provide some evidence that high in-takes of certain classes of fruits or vegetables are associated with reduced risk of individual cancers.

• The results of epidemiological and controlled clinical trials suggest that diets rich in fruits and vegetables can help prevent bone loss.

• The results of prospective cohort studies suggest that high intakes of fruits and vegetables rich in vitamin C and carotenoids may be associated with decreased risk of age-related eye diseases, such as macular degeneration or cataracts.

• Many organizations, including the Centers for Disease Control and Prevention, recommend eating a variety of fruits and vegetables daily; the recommended serving number depends on total caloric intake, which is governed by age, sex, body composition, and physical activity level.