Nut Consumption and Mortality

Bao Y, Han J, Hu FB, et al. Association of nut consumption with total and cause-specific mortality. N Engl J Med. 2013;369(21):2001-2011. 

 

Data from 2 large, long-term, prospective cohort studies were analyzed individually and in combination to locate an association between nut consumption and both total mortality and cause-specific mortality.

 

Data from both the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPS) were used in this analysis. The NHS is a prospective cohort of 121,700 female nurses who were enrolled in 1976. The HPFS is a prospective cohort of 51,529 male health professionals enrolled in 1986. Participants without complete data or who had a history of cancer, heart disease, or stroke were excluded, so the final analyses included 76,464 women and 42,498 men. During the 3,038,853 person-years of follow-up, 16,200 women and 11,229 men had died.

 

Nut consumption was tracked via validated food-frequency questionnaires administered every 2 to 4 years. In the early questionnaires (1980 and 1984), all nuts were grouped together, but later questionnaires separated out consumption of peanuts from tree nuts. Total nut consumption was defined as intake of peanuts and other nuts together. Validation studies confirmed the accuracy of consumption reporting.

 

The primary endpoint was death from any cause. In addition, cause of death was ascertained for 98% of the deaths in each cohort, so this further association could be calculated.

 

Nut consumption was inversely associated with total mortality among both women and men. The hazard ratios (HRs) for dying decreased with increasing nut consumption. Those who reported consuming nuts daily were 20% less likely to have died during the course of the study than those who never ate nuts. 

 

The HRs for death among participants who ate nuts as compared with those who did not were 0.93 (95% confidence interval [CI]: 0.90-0.96) for the consumption of nuts less than once per week; 0.89 (95% CI: 0.86-0.93) for once per week; 0.87 (95% CI: 0.83-0.90) for 2 to 4 times per week; 0.85 (95% CI: 0.79-0.91) for 5 or 6 times per week; and 0.80 (95% CI: 0.73-0.86) for 7 or more times per week (P<0.001 for the trend). Significant inverse associations were also observed between nut consumption and cause of death from cancer, heart disease, and respiratory disease.

 

There are 2 lessons to be learned from this study. The first is obvious: that increasing nut consumption may decrease mortality or, inversely, increase longevity. This study provides further evidence in support of a conclusion most of us already understand as fact. The second, less obvious lesson is that this study can help us understand the world that researchers inhabit, a world that looks different from the one those of us in clinical practice live in.

 

Let’s consider this second idea in depth.

 

The authors of this study have brought us the strongest epidemiological evidence to date that nut consumption improves numerous aspects of health, in particular what we would call “the bottom line”: a person’s risk of dying. The combined cohorts employed along with the long duration of the study provide a database of over 3 million patient years to analyze. The authors were meticulous in trying to neutralize any possible confounders hidden within the data. Every way they broke the data down, they reached the same conclusion: Eating nuts regularly reduced the HR of an individual dying.

 

Nevertheless, they conclude their paper with this statement: “[E]pidemiologic observations establish associations, not causality, and not all findings from observational studies have been confirmed in controlled, randomized clinical trials.” This is how epidemiologists and public health researchers see the world, with greater caution than would seem necessary. Where we might jump to view this research as proof and translate it into practice, they hold back, afraid to commit.

They have reason to be reticent. Randomized controlled trials (RCTs) have had mediocre success in confirming epidemiological predictions. A May 2013 meta-analysis by Moorthy et al¹ that compared the findings of RCTs with the epidemiological data that the trials were meant to confirm suggests we should give little credence to what the epidemiologists tell us. In only 23 out of 34 associations did the results from meta-analyses of epidemiological studies and of RCTs point in the same direction, and in only 6 of those 23 associations were the findings statistically significant. In the remaining 11 out of 34 associations, meta-analyses of epidemiological studies and of RCTs pointed in opposite directions. Of the 12 out of 34 cases in which the association between RCT and epidemiology was statistically significant, only 6 provided results that were predicted by epidemiological studies; the results of the other 6 directly contradicted the prediction made by epidemiologists. Thus Bao et al, the authors of this current study, have good reason to report their findings with some hesitation.

 

Before drawing too many conclusions from the Moorthy et al meta-analysis, we should note that the studies they evaluated come from an era of nutritional science that is fast fading, an era when the cure for a specific disease was often sought in a specific nutrient. In those days, diseases such as scurvy, rickets, pellagra, and spina bifida were cured by single nutrients identified through epidemiological studies. In more recent times, this model of single-nutrient “cause and effect” cure via supplementation has proven less reliable. 

 

One example of the failure of single-nutrient research is the Beta-Carotene and Retinol Efficacy Trial (CARET), which reported that beta-carotene increased rather than lowered risk of lung cancer in smokers.^2-4 Another example is the studies taken from the Selenium and Vitamin E Cancer Prevention Trial (SELECT) that found that vitamin E and selenium increased users’ risk of getting prostate cancer rather than decreasing it.^5,6 Similarly, another SELECT paper reported that increased omega-3 fats in the blood were associated with an increased risk for prostate cancer.⁷

 

We have quickly rationalized the failure of these landmark studies as due to faulty study design or nutrient selection, but a better explanation is that these studies failed because their basic assumption was that a cure could be found in a single nutrient. Biology may not always be that simple. Studying the impact of a whole food like nuts may tell a different story.

 

This journal’s editorial staff had the opportunity to hear Frank Meyskens, Jr, MD, speak at the most recent Society of Integrated Oncology Conference (October 20-22, 2013; Vancouver, BC). Meyskens’ research focuses on cancer prevention, and he was closely involved in the CARET and SELECT research and other similar “failures.” According to Meyskens, researchers need to turn away from the “uni-deficiency model” of disease and consider that the solution may rather be found in the foods people eat. Foods contain multiple nutrients and chemicals that together in combination may have impact on a disease. Foods may “represent the entire biological action package” and therefore may act in ways that single nutrients cannot. Rather than single nutrients, Meyskens now suggests that scientists test “food supplementation or broad dietary change” in populations.⁸

 

In the case of this nut study, incorporation of a “biological action package” into the diet may have benefits in line with epidemiological predictions. While Bao et al may be hesitant to commit to their findings, we need to view their results in the context of many earlier studies. Observational studies and clinical trials suggest that nut consumption has beneficial effects on coronary heart disease and its intermediate biomarkers,^9-11 so much so that in 2003, the Food and Drug Administration concluded that 1.5 oz of nuts per day “may reduce the risk of heart disease.”¹²

 

Additionally, there have been RCTs that suggest multiple benefits from eating nuts. The Prevención con Dieta Mediterránea (PREDIMED) Trial, a large Spanish study that provided people at high risk for cardiovascular disease with supplemental nuts or extra virgin olive oil, reported significant reductions in cardiovascular events in those consuming about 1 oz of nuts per day.¹³ It can be argued that the PREDIMED trial results actually trump this current paper because PREDIMED was a randomized prospective primary prevention trial, and this current study is only observational. Still the sheer size of this trial makes it hard to ignore, in particular in light of earlier studies.

 

This current decrease in HRs is similar to the reduced mortalities reported almost 2 decades ago from the Adventist Health Study (AHS) performed at Loma Linda University, Loma Linda, Calif. In those reports, consumption of nuts 5 or more times per week compared with less than once per week was associated with reduced total mortality, with HRs ranging from 0.56 to 0.82.^14-16 In the intervening years since the AHS studies, nut consumption has been linked to reduction in various mediators of chronic disease, including oxidative stress,¹⁷ inflammation,¹⁸ visceral adiposity,¹⁹ hyperglycemia,²⁰ insulin resistance,²¹ and endothelial dysfunction.²² Prospective cohort studies have associated increased nut intake with reduced risks of type-2 diabetes,²³ metabolic syndrome,²⁴ colon cancer,²⁵ hypertension,²⁶ gallstone disease,²⁷ diverticulitis,²⁸ and even death from inflammatory diseases.²⁹

 

While these past studies have looked at the components of health, this current study looks at the bottom line: mortality. It is difficult to question whether eating nuts is beneficial.

 

This is where our perceptions as clinicians must differ from the view researchers have of the world. They can debate as long as they want, especially if they have tenure. We need to give our patients sound advice today that will improve their health tomorrow. Given the low risk that increased nut consumption has on patient health and the great potential for benefit—ie, decreasing mortality by a fifth—there is little left to debate. We should be actively encouraging our patients to consume a daily serving of nuts.