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Healthy Aging & Lifestyle

ADF for Health and Longevity

By Brady Holmer
Alternate-day fasting (ADF) is a form of intermittent fasting that involves going without food one day and eating the next. ADF has been shown to have metabolic health benefits and may be a lifestyle strategy to promote healthy aging and longevity.

It is no secret that a healthy metabolism is one of the key foundations to living at your best and aging successfully. As we all try to live better, and perhaps longer, it becomes increasingly important to find lifestyle strategies that promote optimal metabolic health, particularly those that are supported by robust science.


One of those strategies, which has seen a spike in interest in recent years, is calorie restriction. As the name suggests, calorie restriction is a dietary regimen that calls for one to reduce their daily intake of calories (energy) by around 15-25 percent. Science shows that energy restriction can activate many evolutionarily conserved pathways in our body that might benefit longevity.

In fact, many scientific studies have found that different forms of calorie restriction can prolong lifespan and healthspan in organisms such as worms, flies, mice, and non-human primates.1 Unfortunately, we don’t know much about the effects of calorie restriction in humans for a few reasons, which will be discussed briefly below.

THE PROBLEM WITH CALORIE RESTRICTION

The interest in the basic cellular and molecular mechanisms of caloric restriction have led researchers to investigate this dietary intervention in “lower order” species. To figure out why (and if) calorie restriction works, it is important to study the effects in organisms like fruit flies before moving up to translational research in people like you and me.

A second reason why lifespan extension using calorie restriction is difficult to study in humans is that chronic restriction of calories is hard for most people, and scientists believe that most dietary restriction regimens are not feasible. Whether due to an incompatibility with lifestyle or the uncomfortable hunger, drastically cutting calories for the long term seems to be aversive to most people. Because of this, the topic has been infrequently and unsuccessfully implemented in the research field.

Luckily, there are alternatives. One such alternative goes by the name intermittent fasting (IF). In contrast to chronic calorie restriction, IF may be a more feasible long-term solution for a healthy metabolism  —  a way to improve biomarkers of health while inadvertently reducing dietary energy intake — “calorie restriction made easy.” Intermittent fasting may also be an effective way to age better.

Alternate-day fasting (ADF) involves “fast” days — where no calories are consumed — and “feast” days — where “unlimited” calories are consumed. Eat one day, fast the next, repeat. Sounds simple, and it is.

ALTERNATE-DAY FASTING 101

One form of intermittent fasting known as alternate-day fasting (ADF) may be particularly useful. ADF involves “fast” days — where no calories are consumed — and “feast” days — where “unlimited” calories are consumed. Eat one day, fast the next, repeat. Sounds simple, and it is. It also might be feasible for more people and provide healthspan and lifespan benefits similar to those observed with calorie restriction.


Many ADF studies have been conducted in overweight individuals or those with diseases like type 2 diabetes to successfully improve weight, metabolism, and cardiovascular health.2,3,4

But what about the effects of alternate-day fasting on aging? Can fasting help “healthy” individuals further improve their metabolism or better yet, promote successful aging and longevity?

Science says, maybe.

ALTERNATE-DAY FASTING AND AGING

Randomized controlled trials, also known as RCTs (the gold-standard way to study the effectiveness of an intervention), have assessed the effects of short-term ADF on a plethora of physiological biomarkers related to aging and longevity. The results are quite promising.

One recent study involved a total of 90 participants between the ages of 48 and 52 years old.5 30 of these were “regular fasters” — people who reported already participating in some type of ADF. These individuals were investigated as a prospective cohort, meaning that researchers looked at how their past lifestyle habits influenced their current health biomarkers, without implementing any experimental intervention.

Another 60 participants were randomized into either an ADF group or a non-ADF (control) group for four weeks. Nobody in these groups reported any previous fasting experience.

Those assigned to the ADF group were told to eat every other day. On the fasting days, no calorie-containing foods or beverages were consumed, and even diet soda was prohibited. They were allowed only water, flavored carbonated water, unsweetened black and green tea, and black coffee.

The non-fasting days placed zero restrictions on the amount or type of food consumed; this is termed ad libitum eating. Essentially, participants were allowed to feast like royalty if they so desired.

The researchers were interested in how alternate-day fasting would influence metabolic health markers, sex hormones, body composition, age-related biomarkers such as oxidative stress, cardiovascular health, and levels of blood ketones, which have been associated with pro-longevity pathways and improved healthspan and lifespan in animals.6

HEALTH-ENHANCING EFFECTS OF ADF

Something very notable about this study was that participants in the ADF group reduced their weekly caloric consumption by about 37 percent. Even without “deliberately” restricting calories on the feast days, energy intake was dramatically reduced. This is quite an impressive reduction. Some human calorie restriction studies haven’t even managed to reduce energy intake by the target goal of 25 percent, (7) suggesting ADF may be even more effective for reducing food intake in those wishing to do so.

ADF caused a significant reduction in body mass index (BMI) and fat mass, and most of this fat loss came from the more “toxic” kind of fat found in the trunk region of the body known as android fat. Participants in the ADF group also improved their lean mass to fat mass ratio.

After just four weeks on the “diet,” blood pressure and arterial stiffness — cardiovascular disease risk factors — were also reduced. These effects are similar to those observed after aerobic exercise training. Participants also lowered their Framingham Risk Score, which is a composite measure of cardiovascular disease (CVD) risk and is used to estimate an individual’s risk for developing CVD within the next 10 years. In this study, risk scores were reduced in the ADF group by 1.4 percent.

ADF also reduced a hormone called triiodothyronine or T3. T3 is one of the thyroid hormones and, in the absence of impaired thyroid gland function, lower levels are linked to increased disease-free lifespan in humans.8

Though participants weren't eating what would be considered a high-fat ketogenic diet, blood samples showed that levels of the ketone body beta-hydroxybutyrate (BHB) were elevated after four weeks of ADF — even on the non-fasting day when blood was sampled.

REGULAR FASTING HAS ANTI-AGING BENEFITS

Let’s talk a bit about the group who was already undergoing ADF before the study took place. Overall, the long-term ADF group reported a lower caloric intake than the control group: eating about 8,700 calories per week compared to 12,300  —  a 28 percent difference.

Compared to the non-fasting group, those who had practiced ADF consistently had lower levels of total cholesterol, low-density lipoprotein (LDL), very low-density lipoprotein (vLDL), and triglycerides. High-density lipoprotein (HDL) was similar in both groups, and the regular fasters had a lower resting heart rate  —  which has also been linked to longevity.9

The good news is that it seems unlikely that regular ADF may be detrimental to long-term health and aging. Bone mass, bone mineral density, white blood cell counts, and other immune-related measures were the same between fasting and non-fasting groups. No iron deficiency was noted in the ADF group, and they also had lower circulating T3 levels but normal thyroid function.

ADF was also associated with a biomarker known as soluble intracellular adhesion molecule 1 (sICAM-1). This pro-inflammatory cytokine is implicated in aging and other diseases,10 and reduced levels suggest a benefit for health and longevity in people who regularly participate in fasting.

HOW FASTING CHANGES YOUR GENES

After 36 hours of fasting, when one of the blood samples were taken, 54 metabolism-related genes were increased by at least 20 percent  —  including genes related to lipids and antioxidants. Another 49 genes were 20 percent lower  —  some of which were related to amino acids like methionine  —  which may be involved in lifespan regulation. Several pathways with implications for aging and longevity were also upregulated, including those related to the essential fatty acids omega-3 and omega-6, mitochondrial fat metabolism, glycogen metabolism, ATP (energy) production, and heat-shock proteins and autophagy.

LIVE FAST, LIVE YOUNG

Fasting for as little as four weeks has some pretty powerful effects — leading to considerable and favorable changes in cardiovascular and metabolic health in already healthy adults. Even better, ADF seems to be a viable, practical way to reduce total food consumption, and something people might actually be able to stick to! Compared to miserable diets, unbearable hunger, or slim-fast shakes, ADF seems much more feasible for weight maintenance and long-term health.

Many individuals enjoy fasting, and find that this way of eating, one which in some ways aligns with how our ancestors would have eaten, is an effective way to manage weight and promote metabolic health. It is also a way to enter into ketosis intermittently, which on its own may have considerable metabolic benefits and could slow aging.

Alternate-day fasting is yet another tool in the “healthy aging toolkit” that you can use to reach your goals. While it’s not for everyone, it may be worth giving it a try, since some of the benefits seem to be realized soon after implementation and, potentially, last a lifetime.

Here’s to your healthy aging journey.

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