Michael Orlich, MD, PHD
Understanding the Adventist Health Study 2: Questions and Answers
The Adventist Health Study 2 (AHS-2) is a large and important study of lifestyle and health among Seventh-day Adventists. It is therefore not surprising that this study would be of interest to Adventist health professionals. The following is a brief introduction to AHS-2, using a question and answer format.
What is the history behind AHS-2?
Early in their history, in the late 19th and early 20th centuries, Seventh-day Adventists developed what may be described as a theology of health and healing, due largely to the extensive writing on this subject by church co-founder Ellen White. This resulted in both the development of a large program of medical and health-promotion work, starting with the Battle Creek Sanitarium under Dr. John Harvey Kellogg, and the promotion and adoption of certain health practices among church members. These included abstention from tobacco and alcohol and the promotion of a vegetarian diet as preferable.
These teachings and practices led to an interest in the mid-20th century among some medical scientists about the potential health effects of Seventh-day Adventist Lifestyle practices, particularly their avoidance of tobacco and the vegetarian diets of some Adventists. In the 1950s and 1960s, Mervyn Hardinge (who along with his doctorate degrees in medicine and pharmacy completed a doctorate in public health at Harvard and became the founding dean of the Loma Linda University School of [Public] Health), published a series of papers about the health of vegetarians, based on a comparison of a small number of vegetarians and non-vegetarians.
Also in the 1950s, other investigators at Loma Linda University, primarily Lemon and Waldon, worked with Wynder of Sloan Kettering on some comparisons of Adventists and others. This led in 1958-60 to a large survey (by Lemon and colleagues) of Adventists, about 23,000 of which were enrolled in the large American Cancer Society Cancer Prevention Study, led by Hammond. We now refer to this study of 23,000 Adventists as the Adventist Mortality Study (AMS).
The AMS demonstrated that Adventists had improved longevity and reduced mortality from respiratory diseases, coronary heart disease, and a number of cancers compared to their non-Adventist counterparts. It was clear that tobacco avoidance might explain many of these findings. These findings prompted a more detailed study of the Adventist lifestyle. Roland Phillips and colleagues, in the 1970s, enrolled approximately 34,000 California Seventh-day Adventists in the Adventist Health Study 1 (AHS-1). Rather than comparing with others (i.e. non-Adventists), the participants of AHS-1 were compared with each other, in an attempt to understand what aspects of diet and lifestyle might be associated with the best health outcomes. One of the most seminal findings from the AHS-1 was association of frequent nut consumption with reduced risk of ischemic heart disease found by Fraser and Sabaté.1,2 Another was the delineation of several factors that contributed to improved longevity among Adventists.3
While the results of AHS-1 were interesting, it seemed apparent that a much larger study would be better able to adequately study the relationship of diet to important health outcomes, particularly specific cancers. Thus, Gary Fraser and colleagues proposed the Adventist Health Study 2 (AHS-2), which was initiated shortly after 2000. It should also be noted that the Adventist Health Studies, which are focused primarily around dietary questions, have spawned subsidiary studies looking at the health effects of air pollution (AHSMOG) and religious and psychosocial factors (ARHS: Adventist Religion and Health Study). Figure 1 portrays the relationship between these studies and their timeframes.
What are the goals of AHS-2, and how is it funded?
AHS-2 is funded primarily by the National Cancer Institute (of the National Institutes of Health) for the purpose of examining the relationship of dietary factors to the risk of common cancers, primarily cancers of the colon and rectum, breast, and prostate.
What type of study is AHS-2?
The AHS-2 is an observational epidemiologic study usually referred to as a cohort study. In a cohort study, a large study population is enrolled, and various characteristics of the cohort members are measured at baseline. The cohort is then followed over time, and outcomes are tracked. Approximately 96,000 Seventh-day Adventists in the United States and Canada were enrolled in the AHS-2 cohort between 2002 and 2007. Approximately one fourth of cohort members are Black, an under-studied population. A detailed questionnaire was used to assess routine dietary habits, other lifestyle factors, and other relevant aspects of the health history. A random sample of about 1000 cohort members was selected to be part of a validation study. Validation study members participated in multiple 24-hour dietary recall assessments over the phone and came to clinics where biometrics were measured and biological samples were obtained. This smaller study is used to validate the accuracy of the larger study’s measurement of diet and even help to adjust for some inaccuracy. All cohort members are sent a small follow-up questionnaire every two years. Incident cancers are tracked by a linkage process with state cancer registries, to which information about diagnosed cancers is reported in a mandatory fashion. We have so far been able to link with the registries of 48 states. This allows for a fairly accurate assessment of the main outcomes.
What are the benefits and limitations of this type of study?
Cohort studies are important tools for studying questions like the impact of diet on the risk of chronic disease and on mortality. Their prospective design, in which exposures are measured before outcomes, helps to eliminate the recall bias and potential reverse-causal associations, which can be problematic in case-control studies. Because they are observational studies, not experimental studies like randomized controlled trials (RCTs), they are subject to confounding, in which an association between the exposure of interest and the outcome is not causal, but is due to some other factor which causes the outcome and is in some way linked to the exposure. Much work goes into using statistical methods to measure such potential confounding factors and to adjust for their effect in statistical analyses.
In the area of diet and chronic disease, it is very difficult to do RCTs, because they have to be very large and last for a long time, and are thus very costly. Small RCTs can examine the effects of diet on risk factors, biomarkers, or intermediate outcomes, and help explore potential mechanisms. But much of what we have learned scientifically about diet and health has been from observational cohorts like the Framingham Study, the Nurses Health Study, and the Adventist Health Studies.
What dietary factors are being examined?
The most notable feature of the AHS-2, compared to similar cohort studies, is the relatively large percentage of persons consuming various vegetarian diets. Table 1 shows the five dietary patterns defined by AHS-2 investigators, and the approximate percentage of AHS-2 participants who fall into each category. Comparisons are made of the vegetarian dietary patterns to the non-vegetarian pattern. In addition, the AHS-2 questionnaire can be used to examine the intake of many specific foods and nutrients. We can therefore test hypotheses about specific foods and cancers: for example, how does the consumption of soy foods relate to the risk of breast cancer?
What have we learned from AHS-2 about the health effects of vegetarian diets?
Vegetarian dietary patterns have been associated with a number of health benefits in AHS-2 compared to a non-vegetarian dietary pattern. Vegetarians have a lower BMI than non-vegetarians on average, with vegans having the lowest.4 After adjustment for several potential confounders, vegetarian dietary patterns in AHS-2 are associated with both a lower prevalence4 and incidence5 of (self-reported) diabetes mellitus. Within the validation subsample (N = approx. 1000) in which blood pressures and laboratory values were measured, vegetarian dietary patterns were associated with lower blood pressures6,7 and a reduced risk of metabolic syndrome.8 After about 6 years of follow-up, all vegetarians had a 12% relative reduction in mortality from natural causes (hazard ratio [HR] = 0.88, 95% confidence interval [CI] 0.80-0.97), an affect seen primarily among men.9 Compared to non-vegetarians, the relative mortality for vegans was 0.85 (95% CI 0.73-1.01), for lacto-ovo-vegetarians 0.91 (95% CI 0.82-1.00), and for pesco-vegetarians 0.81 (95% CI 0.69-0.94).9
In the next year or so, we expect to publish findings regarding the association of vegetarian dietary patterns (and a number of specific foods and nutrients) to the risk of colorectal cancer, breast cancer, and prostate cancer. We are also seeking to explore many other interesting questions in the coming years (where funding can be obtained) including the relationship of diet to neurological diseases, congestive heart failure, gene expression, and the microbiome.
How can I learn more about the Adventist Health Study 2?
You can read more about AHS-2 at www.adventisthealthstudy.org. Among other items, you will find a list of scientific publications from AHS-2 and previous studies, which will provide detailed information about methods and findings.
A word of gratitude
The investigators of AHS-2 would like to express their sincere appreciation to the many readers who have supported the study. Many of you are participants in the cohort. The collective participation of individuals like you is what makes this study possible. Many of you have also helped with recruitment and retention efforts at the local church level. As Adventist health professionals, you often help to take the information learned from the Adventist Health Studies and translate it in responsible ways in your health promotion efforts with patients and in the church setting. We realize that your support stems from a strong faith commitment, and we hope that you will continue to find the results of AHS-2 a valuable source of scientific information about the possible effects of faith-motivated diet and lifestyle choices.
References
- Fraser GE, Sabate J, Beeson WL, Strahan TM. A possible protective effect of nut consumption on risk of coronary heart disease. The Adventist Health Study. Arch Intern Med. 1992;152(7):1416-1424.
- Sabate J. Does nut consumption protect against ischaemic heart disease? Eur J Clin Nutr. 1993.
- Fraser GE, Shavlik DJ. Ten years of life: Is it a matter of choice? Arch Intern Med. 2001;161(13):1645-1652.
- Tonstad S, Butler TL, Yan R, Fraser GE. Type of vegetarian diet, body weight, and prevalence of type 2 diabetes. Diabetes Care. 2009;32(5):791-796. doi:10.2337/dc08-1886.
- Tonstad S, Stewart K, Oda K, Batech M, Herring RP, Fraser GE. Vegetarian diets and incidence of diabetes in the Adventist Health Study-2. Nutr Metab Cardiovasc Dis. 2013;23(4):292-299. doi:10.1016/j.numecd.2011.07.004.
- Pettersen BJ, Anousheh R, Fan J, Jaceldo-Siegl K, Fraser GE. Vegetarian diets and blood pressure among white subjects: results from the Adventist Health Study-2 (AHS-2). PHN. 2012;15(10):1909-1916. doi:10.1017/S1368980011003454.
- Fraser GE, Katuli S, Anousheh R, Knutsen SF, Herring P, Fan J. Vegetarian diets and cardiovascular risk factors in black members of the Adventist Health Study-2. PHN. 2014:1-9. doi:10.1017/S1368980014000263.
- Rizzo NS, Sabate J, Jaceldo-Siegl K, Fraser GE. Vegetarian dietary patterns are associated with a lower risk of metabolic syndrome: the adventist health study 2. Diabetes Care. 2011;34(5):1225-1227. doi:10.2337/dc10-1221.
- Orlich MJ, Singh PN, Sabate J, et al. Vegetarian Dietary Patterns and Mortality in Adventist Health Study 2. JAMA Intern Med. 2013;173(13):1230-1238. doi:10.1001/jamainternmed.2013.6473.
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