The Utah population consistently has one of the lowest rates of death due to cardiovascular disease,(1
) and this low-risk status has been linked to the lifestyle of people with an LDS religious preference.(2
) The most likely source of such risk differences is the proscription of tobacco smoking since smoking is a well-described risk factor for CAD development and conveys a substantial increase in risk,(1
) but it is improbable that smoking alone could account for such a profound effect.
This study confirmed an additional CAD risk difference based on routine fasting behavior and is the first to evaluate the association of routine fasting with angiographically-defined CAD. Fasting was defined in the study as abstinence from food and drink for an extended time period. This was designed to include the LDS definition and a broader set of other fasting definitions while retaining the periodic and routine aspects. Many religions encourage occasional fasting for purification and improving self-discipline,(21
) and some contemporary wellness philosophies advocate prolonged fasting for bodily cleansing. LDS teachings provide for a once-monthly fast wherein adherents do not eat or drink for two consecutive meals (i.e., 24 hours) and children are encouraged to fast as early as the age of eight years, thus potentially establishing a pattern of fasting behavior early in life prior to the development of CAD.(8
The lower risk of CAD herein may have occurred because fasting, or a behavior arising from it, is causally related to lower CAD risk. It may be that fasting improves an individual’s self-control over bodily appetites and desires,(8
) which could translate to better discipline regarding daily caloric intake. Since this study did not evaluate caloric intake (i.e., diet), it is not clear whether diet or some dietary factor (e.g., vitamin, nutrient, or nutraceutical intake) may account for the finding. Since fasting-derived behavioral discipline (i.e., a “state of mind”) may account for the lower risk of CAD associated with fasting in this population, future investigation should evaluate dietary factors and self-discipline.
In contrast, the hypothesis that fasting may influence metabolic health is the more likely explanation based on evidence from the scientific literature. Decreased β-cell sensitivity to glucose (derangement of insulin secretion) and decreased sensitivity to insulin by peripheral tissues (insulin resistance) are well-established pathways in type II diabetes.(13
) Desensitization of receptors to a stimulus is a well-known phenomenon that may occur quickly or after prolonged exposure to the stimulus.(13
) Because it periodically eliminates such exposure, routine fasting may represent a behavioral approach to temporarily eliminate receptor stimulation and reset cellular sensitivity to glucose and/or insulin by periodically resting the system.(11
) If so, fasting would be associated not only with lower risk of CAD but also with lower prevalence of diabetes, and this study found such associations. Because 18% of diabetics reported that they routinely fast and had a lower risk of CAD compared to non-fasting diabetics, this suggests that fasting may reduce diabetes risk and this should be further investigated.
Regarding glucose metabolism, Panowski and colleagues found that expression of the Caenorhabditis elegans
PHA-4 gene was increased more than 80% due to fasting and, in separate experiments, that over-expression of PHA-4 increased longevity.(23
) The murine and human FOXA genes are orthologous to the C. elegans
PHA-4 gene. FOXA is a family of transcription factors that, among other things, regulate glucagon expression and glucose homeostasis, and do so to a greater degree in response to fasting.(24
) Other transporter and metabolic enzyme genes are also differentially expressed due to fasting,(25
) and new evidence suggests that fasting (termed “short-term starvation”) may activate a self-protective cellular stress-resistance mechanism.(26
) Such direct impacts of fasting on longevity and homeostasis provide biologically plausible mechanisms that may explain how routine fasting behavior across the life span could reduce age-related chronic diseases such as CAD.
It may be instructive to also consider other populations where fasting behavior may be linked to diabetes or metabolic syndrome. It is increasingly evident that several ethnic populations whose ancestors historically experienced more frequent and severe feast-famine cycles than Caucasians did are today enduring higher rates of diabetes and metabolic syndrome.(27
) The higher rates of disease among those ethnic groups is the result of both modern environmental factors and a shared genetic ability to withstand extended periods without food,(27
) which may also be described as the inherited ability to endure more frequent periods of fasting or caloric restriction.
Several reports indicate that limiting caloric intake (i.e., “caloric restriction”) may have anti-aging (13
) and cardio-protective effects.(9
) It is expected that caloric restriction will lead to improved cardiac risk profiles.(9
) While fasting was associated with lower diabetes prevalence, only small and not statistically-significant differences in BMI and hypertension were found based on fasting behavior. Evidence suggests that multiple calorie-deprivation pathways may exist that improve health,(23
) thus any direct connection between fasting and caloric restriction requires further exploration.
Finally, evidence herein also suggests that fasting is associated with other behaviors common to this population. Patients who fasted were also more likely to not smoke, be more physically active, follow beverage proscriptions, engage in religious worship, and observe a day of rest. This allows for the possibility that fasting may simply be the best surrogate for a cluster of low-risk behaviors, including unmeasured factors. Fasting behavior was, however, reported by some with religious preferences other than LDS and, among these participants, an association of large effect size was found (a 77% lower risk of CAD). This suggests that the observed benefit arises from fasting and not from a cluster of religion-associated behaviors. Further, it is also unlikely that the other behaviors (at least the measured ones) account for the fasting benefit since they were all eliminated when statistical modeling included them along with fasting.
This study is potentially susceptible to various problems faced by all observational studies, including uncontrolled confounding, reverse causation, and self-selection in survey response. The association of religious preference with CAD was similar in both populations, though, and adjustment for various potential confounders did not eliminate or appreciably attenuate the association of fasting. Confirmatory studies in other populations are required since uncontrolled confounding may remain, including due to patient self-selection for survey response in this study’s hospital care setting.
The LDS proscription of alcohol is notable since non-use is associated in many studies with higher CAD risk compared to moderate levels of consumption.(4
) If so, CAD risk would be expected to increase among LDS adherents, but this study suggests that abstinence from alcohol is not associated with higher CAD risk. While contrary to a commonly-held belief, this finding is supported by reports that the benefits of moderate alcohol consumption may arise from residual confounding due to socioeconomic and other factors,(28
) an issue that only a randomized clinical trial could resolve. The current study appears to be the first wherein the majority of participants were non-drinkers, thus the social and behavioral risk profiles of drinkers and non-drinkers herein may be at variance with previously-studied populations.
This population is unique because of the aforementioned behaviors and the primarily Caucasian ethnic composition, thus the study findings may not be generalizable to other populations. Further study of fasting in other geographic locations and among other ethnicities is indicated.
A strength of the study was the CAD outcome that was determined from coronary angiography, the gold-standard assessment of CAD status. Cases had clinically-significant coronary stenoses. Controls, although not a random population sample, were definitively free from coronary lesions.