Jacob Schor

December 10, 2019

It’s When You Eat Not What You Eat.

We’ve spent more time on the road traveling by car from one place to another in the past six months than perhaps the last twenty years.  Though we’ve been lucky to spend an occasional night at the homes of friends, often we’ve resorted to roadside hotels.

Starting in the mid-1990s America’s medium priced hotel chains have started offering free breakfasts as a way to compete in the market place rather; Apparently it is more profitable for them than lowering their room rates.  In 2012, 79% of hotels offered complimentary breakfast, up from 55% in 2010, according to the American Hotel & Lodging Association. [1] Today more than 90% of midscale hotels offer this bait not so much to draw guests in any longer but to keep up with the competition.  Competition is incrementally improving the breakfast options.  One server in Kansas bragged to me how she bakes the premade frozen omelets her hotel offers rather than merely microwaving them. 

What one can’t help but notice is how routine American breakfast choices are.  Though they may brag about the wide selection of toppings one can choose from, the basic menu varies little.  My observation is that the most popular breakfast is waffles.  Almost every roadside hotel in America offers them (though a few still use the pancake conveyor belts).  Massive sections of the country also offer biscuits and gravy.  Eggs, some form of pork meat (bacon, sausage, ham or imitation sausage made from turkey) and toasted bread, bagels, English muffins, pastries, doughnuts and so on complete the list.  To the side there is usually a refrigerator stocked with yogurts, sometimes a crockpot of oatmeal and of course Fruit Loops and other dried cereals to choose from.

Free breakfast? The advertisements tend to look better than the real thing.

Seeing this firsthand, and even occasionally succumbing to temptation has left me thinking about what we should eat for breakfast.  Thus, I was, shall we say, hungry for the information that has been reported in several recent papers that suggest that what we choose to eat for breakfast might not be as important as if and when we choose to eat breakfast.  

In April 2019, Rong and colleagues reported that people who habitually skip breakfast were at higher risk of dying from any cause and in particular heart disease than people who regularly ate breakfast. [2]  This prospective study followed a cohort of 6,550 U.S. adults, 40 to 75 years of age, who participated in the National Health and Nutrition Examination Survey III 1988 to 1994. Frequency of breakfast eating was recorded during in-house interviews. Death and underlying causes of death were ascertained by linkage to death records through December 31, 2011. In following this cohort for 17 to 23 years, skipping breakfast was associated with a significantly increased risk of mortality from cardiovascular disease.  Of the cohort, 59% consumed breakfast daily. The other 40% ate breakfast less frequently: 5% never ate breakfast; 11% rarely ate breakfast, 25% ate only on some days.  The study recorded data of 112,148 person-years during which 2,318 deaths occurred, including 619 deaths from cardiovascular disease (CVD).  That’s a lot of data to draw from.

After all the adjustments were made for age, sex, race/ethnicity, socioeconomic status, dietary and lifestyle factors, body mass index, and cardiovascular risk factors, and so on, the researchers were left with what seem to be shocking conclusions. Study participants who never consumed breakfast compared with people who ate breakfast daily were almost twice as likely to die of heart disease and almost 20% more likely to die of any cause.  (CVD hazard ratios 1.87 (95% confidence interval: 1.14 to 3.04) and 1.19 (95% confidence interval: 0.99 to 1.42) for all-cause mortality). The later upward trend did not reach statistical significance. 

After adjustment for just age, sex, and race/ethnicity, participants who never consumed breakfast had a 75% higher risk of all-cause mortality (hazard ratio [HR]: 1.75; 95% confidence interval [CI]: 1.46 to 2.10) and 2.58-fold higher risk of cardiovascular mortality (HR: 2.58; 95% CI: 1.64 to 4.06) compared with those who consumed breakfast every day.  The associations of breakfast eating with heart disease–specific and stroke-specific mortality were examined further. 

Compared with those who consumed breakfast every day, participants who never consumed breakfast had a higher risk of heart disease–specific mortality (HR: 2.34; 95% CI: 1.44 to 3.80) and stroke-specific mortality (HR: 3.53; 95% CI: 1.40 to 8.95) in models adjusted for just age, sex, race/ethnicity. In the fully-adjusted model, the association between skipping breakfast and stroke-specific mortality remained significant (HR: 3.39; 95% CI: 1.40 to 8.24).

According to this study regularly eating breakfast reduces risk of dying from cardiovascular disease and probably stroke.…. or put the other way around, not eating breakfast raises risk significantly.   Thus, it seems like a no-brainer that we should make an effort to foster a habit of eating breakfast in our patients.  Can you think of any other lifestyle habit that cuts risk of dying to such a degree?

And honestly looking at some of these hotel buffet lines, I’ve read this study over again as it is hard to believe one wouldn’t be better off skipping the experience entirely.

More people die of cardiovascular disease than any other cause, not just in the United States but worldwide.   Even small decreases in risk have the potential of having large impacts on disease and suffering.  Could those free hotel breakfasts be cutting deaths to this degree?  Personally, I wake up hungry in the morning and can’t imagine not eating breakfast.  Yet surveys suggest that almost a quarter of younger people now skip breakfast. [3] [4]

Evidence from other papers suggests that skipping breakfast is associated with increased risk of obesity [5], dyslipidemia [6], hypertension [7], type 2 diabetes [8], metabolic syndrome [9], coronary heart disease [10], and cerebrovascular disease [11].

This is not the first study to suggest bad associations with skipped breakfasts.  Cahill et al reported in 2013 that they had assessed the eating habits of 26,902 American men from the Health Professionals Follow-up Study.  During a 16-year period, 1527 cases of heart disease were diagnosed among these men.  Men who skipped breakfast had a 27% higher risk of CHD compared with men who did not (relative risk, 1.27; 95% confidence interval, 1.06-1.53). Furthermore, we should note that men who ate late at night had a 55% higher CHD risk compared with men who did not eat late at night, (relative risk, 1.55; 95% confidence interval, 1.05-2.29). [12]

Kubota et al reported results in a 2016 paper from a large group of Japanese that included 82,772 participants (38,676 men and 44,096 women).   Those people who skipped breakfast had a 14% greater risk of CVD, and 18% increased risk of stroke and a 36% greater risk of hemorrhagic stroke.  [13]

Before we try to digest this information, I want to stir in the findings from another study, a small clinical trial conducted by Wilkinson et al that was published in December 2019. The authors recruited 25 people with diagnosed metabolic syndrome from hospital outpatient clinics at the University of California in San Diego medical school.  They convinced these patients to follow a Time Restricted Eating diet for 12-weeks.

Animal studies have pretty definitively shown that time-restricted feeding (TRF) prevents and reverses metabolic diseases. Human studies have suggested time-restricted eating (TRE) reduces risk of metabolic diseases in people as well. Thus, Wilkinson and colleagues conducted this single-arm, paired-sample trial

Though they started with twenty-five participants in the trial only 19 (13 men and 6 women) made it to the final analysis.  Not only did they all have metabolic disease, they were being treated with drugs to control their condition; the majority of the participants were on a statin and/or antihypertensive therapy. All met a minimum of three of the criteria for metabolic syndrome (MS).  At baseline, the mean daily eating window of participants was ≥14 hours.  

The participants followed a 10-hour Time Restricted Eating (TRE) diet for 12-weeks.  All foods consumed during the day had to be eaten in a 10-hour period.

The effects were striking.  Nearly every marker of metabolic disease improved significantly. Participants experienced improved sleep as well as a 3-4 percent reduction in body weight, body mass index, abdominal fat and waist circumference. Major risk factors for heart disease were diminished as participants showed reduced blood pressure and total cholesterol. Blood sugar levels and insulin levels trended toward improvement. [14]

Metabolic syndrome isn’t as definitive an endpoint as dying of heart disease but it does raise risk of diabetes by five-fold and doubles risk of heart disease.  Thus, one must assume that lowering metabolic syndrome will eventually translate into lowering risk of dying from heart disease.  

This Wilkinson study tested only “eating duration”, that is the number of hours between the first and last time that one consumes any calories during the 24-hour day.  We should sidetrack and explain that when this dietary thing is done to animals it is referred to as Time Restricted Feeding but in humans, who feed themselves, the name is changed to Time Restricted Eating.   Also note that TRE is the flip side of what is called Night-Time Fasting.  In Catherine Marinac’s paper on night-time fasting and breast cancer risk, benefit was associated with night-time fasting for 13 hours or more per night as compared to 12 hours or less. [15]

In this Wilkinson study, the clock is flipped and the total daily interval when meals are consumed is counted instead of the time period spent not eating.  Thus, a ten-hour time restricted eating intervention could also be described as a fourteen-hour night-time fast.  It’s that whole cup half full versus the cup half empty business.  Both are describing the same thing.  The only difference is that eating may sound more appealing to patients than fasting and this name change may increase patient compliance.

In recent years we have become aware that the health impact of food is not only a matter of what a person eats but also of when they eat, especially in relation to their sleep cycle.  One current theory suggests this TRE effect is related to circadian cycles. The body is more efficient at digesting food and drink when a person is active and when light is present.  Eating or drinking at night, when it is dark, appears to disrupt the body systems and impact metabolism negatively.  A consistent daily cycle of eating and fasting nurtures the circadian clock to optimize metabolism.  At least in rodents a regular schedule of eating and fasting keeps them healthier. [16]

Several theories have been floated to explain why skipping breakfast could be so harmful.  Skipping breakfast might lead to overeating later in the day and impaired insulin sensitivity.[17]  Eating breakfast helps regulate the appetite and improves the glycemic response at the next meal increasing insulin sensitivity. [18]  Skipping breakfast is stressful and the longer period of fasting leads to elevated blood pressure in the morning because of a hypothalamic-pituitary adrenal triggered response. [19] It also may be a simple marker of general poor lifestyle choices,

The studies that tell us breakfast skipping is associated DM-2, obesity, and CVD also associate breakfast skipping with late-night eating, variable eating patterns, increased high-fat/ high-sugar snacking and reduced fruit and vegetable consumption. [20] [21] So maybe it is not that skipping breakfast that is the problem as much as what these breakfast-skippers choose to eat and how they live the rest of the day. Asking a patient if they skip breakfast could be just a screening question that reveals a full pattern of poor lifestyle choices.  It could be similar to how intake forms once asked new patients whether they used a seatbelt while driving (automatic seatbelts and alarm buzzers that force compliance have made this query less useful).  

At the same time, the standard American breakfast is far from perfect.  Americans are perhaps unique in the world; we have a very specific and limited image of what we think breakfast foods are.  People in the rest of the world select from a far wider range of food choices for their first meal of the day than Americans do.  People might be far better off substituting what they eat for dinner for their breakfast.  Yet to do so would require changing deeply ingrained beliefs that might not be easily amenable to change. [22]  It’s probably eating in the morning that pro9vides the benefit of breakfast, not the foods Americans choose to eat for breakfast.  Thus one might suspect that we could see more benefit from better breakfast choices.

How does this Time Restricted Eating thing fit in with the other eating strategies people are into these days?  I’m thinking of calorie restriction (CR) or intermittent fasting (IF) in particular that emphasize calorie reduction.  These strategies may change the daily eating duration even if not done so consciously. Time-Restricted Feeding/Eating is different from these caloric restriction strategies in that there is no requirement to reduce caloric intake.  It just requires consistently limiting consumption to a specific time interval.  The evidence to date suggests that this alone may improve metabolism and cardiovascular health by improving circadian clock function.  The benefit on diabetes suggested by the Wilkinson study is consistent with data from research on mice.   Benefits from TRE occur even without weight loss.

This is far from simple. Valter Longo, a major proponent of caloric restricted diets suggested in a 2016 paper that eating patterns such as this TRE diet may mimic the metabolic changes brought about by fasting and be useful in designing ‘fasting mimicking diets.’[23]  

These recent additions to the medical literature give us some basis to what we might tell patients about meal timing.  It is probably better to eat our largest meals, in particular our high fat meals, during our active, daytime period.  Allowing mice to consume high fat meals during their rest period encourages metabolic disease. In humans eating close to when melatonin begins to rise leads to greater fat deposition. Eating earlier in the day leads to greater weight loss in women.  

Insulin sensitivity is greater in the morning. Perhaps this is an argument in favor of those make-our-own hotel waffles? Larger meals are processed more effectively when eaten in the first half of the day.  Melatonin does however reduce insulin release and so the body has a harder time processing glucose at night or early in the morning when melatonin is still elevated. [24] This might argue against those waffles, or perhaps, holding off eating breakfast until the last second before checking out of the hotel.  Taking advantage of the ubiquitous work out rooms and pools the hotels seem to have might be a good idea.  We should encourage patients to eat their large meals early in the day and to avoid eating for a few hours before bed, especially carb loaded bedtime snacks. 

Given the Wilkinson et al results, we clearly have a new and novel strategy for treating metabolic syndrome and probably also type-2 diabetes.  Going too long in the morning without breakfast does not seem like a great idea even if we rationalize and discount the breakfast skipping studies.  For sure, skipping breakfast ‘may be a behavioral marker for unhealthy dietary and lifestyle habits.’ Teenagers who skip breakfast tend to exhibit a list of other traits that may also put their health at risk, for example, eating more fast food having more emotional problems. [25]  

There remain good arguments to eat in the morning. Eating breakfast lowers blood pressure and reduces arterial stiffness. This is why measurements of these parameters are done in a fasting state. [26]  Skipping breakfast may also trigger unwanted changes in blood lipids, in particular increased LDL cholesterol. [27]  Whatever the reasons why, we need to assume skipping breakfast increases risk with cardiovascular disease.  So, Time Restricted Eating but not skipping breakfast.  Of course, this is going to confuse many of our patients, especially if breakfast to them, looks like what America’s hotels offer them.

Ever since Carol Marinac’s 2016 paper, we’ve been promoting the benefit of longer night-time fasting to lower risk of breast cancer recurrence. That data suggested that a night-time fast of greater than 13 hours benefited to women with a history of breast cancer. [28]

The problem with encouraging this is that many women have fulfilled our suggestion by simply skipping breakfast.  The resultant increase in CVD risk might outweigh any breast cancer risk reduction.  We need an approach that will allow both a longer night-time fast and still encourage eating breakfast and the obvious solution would be to eat an earlier dinner. Such a meal pattern of eating an early dinner was encouraged by Kogevinas et al’s 2018 study. In their results, compared to participants who went to sleep immediately or shortly after supper, those who delayed going to sleep for 2 or more hours after supper had a 20% reduction in risk for breast and prostate cancer combined (adjusted odds ratio [OR]: 0.80; 95% confidence interval [CI]: 0.67-0.96) and in each cancer individually (prostate cancer OR: 0.74; 95% CI: 0.55-0.99 and breast cancer OR: 0.84; 95% CI: 0.67-1.06).  [29]

If we combine Kogevinas’ findings with Marianac’s, and add them to Wilkinson’s and Rong’s, then we should encourage an early dinner, two hours before bedtime, for example 6 pm, bed at 8 pm and then breakfast 14 hours later, at 8 am.  Did I get the math right?

Timed Restricted Eating: Eat for only 10 hours per day: 8 AM (start breakfast) to 6 PM (end of dinner) eating interval

Largest Meal: Eat it mid-day

Sleep, 8 PM or later. Minimum two hours after last meal.

Admittedly this is all rather strange, at least for those of us who have been so focused on that “You are what you eat” thing for so many years.  When you eat may be as important or possibly more important than what you eat.  Given all that, I still have not yet tried eating a hotel waffle.

.  

The thing we have not even touched on here is the harm caused by ultra-processed foods but let’s save that for another day.  

Other related meal timing articles:

https://www.naturalmedicinejournal.com/journal/2016-09/nightly-fasting-improves-breast-cancer-prognosis

https://www.naturalmedicinejournal.com/journal/2018-10/early-supper-and-late-bed-may-lower-cancer-risk

https://www.naturalmedicinejournal.com/journal/2018-12/processed-foods-increase-risk-cancer


[1] https://www.usatoday.com/story/travel/hotels/2013/05/20/hotels-free-meals/2344127/

[2] Rong S, Snetselaar LG, Xu G, et al.  Association of Skipping Breakfast With Cardiovascular and All-Cause Mortality. J Am Coll Cardiol. 2019 Apr 30;73(16):2025-2032. 

[3] Haines PS, Guilkey DK, Popkin BM. Trends in breakfast consumption of US adults between 1965 and 1991. J Am Diet Assoc 1996;96:464–70.

[4] Kant AK, Graubard BI. 40-year trends in meal and snack eating behaviors of American adults. J Acad Nutr Diet 2015;115:50–63.

[5] van der Heijden AA, Hu FB, Rimm EB, van Dam RM. A prospective study of breakfast con-sumption and weight gain among U.S. men. Obesity (Silver Spring) 2007;15:2463–9.

[6] Smith KJ, Gall SL, McNaughton SA, Blizzard L, Dwyer T, Venn AJ. Skipping breakfast: longitudinal associations with cardiometabolic risk factors in the Childhood Determinants of Adult Health Study. Am J Clin Nutr 2010;92:1316–25.

[7]  Witbracht M, Keim NL, Forester S, Widaman A, Laugero K. Female breakfast skippers display a disrupted cortisol rhythm and elevated blood pressure. Physiol Behav 2015;140:215–21.

[8] Ballon A, Neuenschwander M, Schlesinger S. Breakfast skipping is associated with increased risk of type 2 diabetes among adults: a systematic review and meta-analysis of prospective cohort studies. J Nutr 2019;149:106–13.

[9] Odegaard AO, Jacobs DR Jr., Steffen LM, Van Horn L, Ludwig DS, Pereira MA. Breakfast frequency and development of metabolic risk. Diabetes Care 2013;36:3100–6.

[10] Cahill LE, Chiuve SE, Mekary RA, et al. Prospective study of breakfast eating and incident coronary heart disease in a cohort of male US health professionals. Circulation 2013;128:337–43.

[11] Kubota Y, Iso H, Sawada N, Tsugane S, Group JS. Association of breakfast intake with incident stroke and coronary heart disease: the Japan Public Health Center-Based Study. Stroke 2016;47:477–81.

[12] Cahill LE, Chiuve SE, Mekary RA, et al. Prospective study of breakfast eating and incident coronary heart disease in a cohort of male US health professionals. Circulation 2013;128:337–43.

[13] Kubota Y, Iso H, Sawada N, Tsugane S, Group JS. Association of breakfast intake with incident stroke and coronary heart disease: the Japan Public Health Center-Based Study. Stroke 2016;47:477–81.

[14] Wilkinson MJ, Manoogian ENC, Zadourian A, et al. Ten-Hour Time-Restricted Eating Reduces Weight, Blood Pressure, and Atherogenic Lipids in Patients with Metabolic Syndrome. Cell Metabolism, 2019; Dec 2. pii: S1550-4131(19)30611-4.

[15] Marinac CR, Nelson SH, Breen CI, et al. Prolonged Nightly Fasting and Breast Cancer Prognosis. JAMA Oncol. 2016 Aug 1;2(8):1049-55. 

[16] Manoogian ENC, Chaix A, Panda S. When to Eat: The Importance of Eating Patterns in Health and Disease.  J Biol Rhythms. 2019 Dec 8:748730419892105. 

[17]  Astbury NM, Taylor MA, Macdonald IA. Breakfast consumption affects appetite, energy intake, and the metabolic and endocrine responses to foods consumed later in the day in male habitual breakfast eaters. J Nutr 2011;141: 1381–9.

[18] Gwin JA, Leidy HJ. A review of the evidence surrounding the effects of breakfast consumption on mechanisms of weight management. Adv Nutr 2018;9:717–25.

[19] Witbracht M, Keim NL, Forester S, Widaman A, Laugero K. Female breakfast skippers display a disrupted cortisol rhythm and elevated blood pressure. Physiol Behav 2015;140:215–21.

[20] Bi H, Gan Y, Yang C, et al. Breakfast skipping and the risk of type 2 diabetes: a meta-analysis of observational studies. Public Health Nutr. 2015 Nov;18(16):3013-9. 

[21] Ofori-Asenso R, Owen AJ, Liew. Skipping Breakfast and the Risk of Cardiovascular Disease and Death: A Systematic Review of Prospective Cohort Studies in Primary Prevention Settings. J Cardiovasc Dev Dis. 2019 Aug 22;6(3). pii: E30. 

[22] Bian L, Markman EM. Why do we eat cereal but not lamb chops at breakfast? Investigating Americans’ beliefs about breakfast foods. Appetite. 2020 Jan 1;144:104458. 

[23] Longo VD, Panda S.  Fasting, Circadian Rhythms, and Time-Restricted Feeding in Healthy Lifespan. Cell Metab. 2016 Jun 14;23(6):1048-1059.

[24] Manoogian ENC, Chaix A, Panda S. When to Eat: The Importance of Eating Patterns in Health and Disease.  J Biol Rhythms. 2019 Dec 8:748730419892105

https://journals.sagepub.com/doi/pdf/10.1177/0748730419892105

[25] Park S, Rim SJ, Lee JH2. Associations between dietary behaviours and perceived physical and mental health status among Korean adolescents. Nutr Diet. 2018 Nov;75(5):488-493. 

[26] Ahuja KD, Robertson IK, Ball MJ. Acute effects of food on postprandial blood pressure and measures of arterial stiffness in healthy humans. Am J Clin Nutr 2009;90:298–303.  

[27] Smith KJ, Gall SL, McNaughton SA, Blizzard L, Dwyer T, Venn AJ. Skipping breakfast: longitudinal associations with cardiometabolic risk factors in the Childhood Determinants of Adult Health Study. Am J Clin Nutr 2010;92:1316–25.

[28] Marinac CR, Nelson SH, Breen CI, et al. Prolonged nightly fasting and breast cancer prognosis [published online ahead of print March 31, 2016]. JAMA Oncol

[29] Kogevinas M, Espinosa A, Castelló A, et al. Effect of mistimed eating patterns on breast and prostate cancer risk (MCC-Spain Study). Int J Cancer. 2018 Nov 15;143(10):2380-2389.