How Does Time Restricted Eating and Intermittent Fasting Work? Part II

How Does Time Restricted Eating and Intermittent Fasting Work? Part II

Intermittent fasting or IF is a practice involving alternating fasting time and/or calorie restriction with periods of feeding that has proven cellular benefits, metabolic gains and remission or reversal for a variety of symptoms and disease states. Time restricted eating is compressing an eating window to a specific number of hours each day. An example of this would be eating all the day’s food within a 6–8-hour window. 

With the prevalence of obesity and chronic disease impacting our healthspan and quality of life, implementing the practices of intermittent fasting or time restricted eating may prove to be an important lifestyle tool for maintaining health and vitality as we age.

In Part One of this series, I went into detail about how intermittent fasting and time restricted eating works along with the long list of health benefits that have been linked to these lifestyle tools. In today’s article, Part Two takes a more practical view regarding the different ways to structure intermittent fasting and time restricted eating. We will also cover some of the most common questions about the safety and details of these two lifestyle practices. This will essentially be a guide to intermittent fasting and time restricted eating for beginners and experienced fasters alike.

This article covers the following topics:

  • How to intermittent fast
  • How to do time restricted eating
  • Is intermittent fasting and time restricted eating safe?
  • Are these two practices different for men and women?
  • Can you drink coffee or tea?
  • Does intermittent fasting and time restricted eating promote weight loss?
  • Can a ketogenic diet be combined with intermittent fasting and time restricted eating?

By the end of this article, you’ll know if intermittent fasting and time restricted eating are for you and how to get started.

Time restricted eating meal plan hours – 16:8, 18:6, and 20:4

There are many ways to implement a time restricted eating and/or intermittent fasting plan. Let’s look at some of the most popular schedules for time restricted eating and intermittent fasting.

Type of time restricted eating or intermittent fastingExplanationSample scheduleWhat to eat in your windowTips
Time restricted feeding (TRF)Fast for 16 hours overnight and condense meals into an 8-hour windowFinish dinner by 8 pm then fast until 12 pm the next dayRegular dietMay be practiced daily or a few times per week
Time restricted feeding 18:6 (TRF)Fast for 18 hours overnight and condense meals into a 6-hour eating windowFinish dinner by 6 pm and fast until 12 pm the next dayRegular dietMay be practiced daily or a few times per week
Time restricted feeding 20:4 (TRF)Fast for 20 hours overnight and condense meals into a 4-hour eating windowFinish dinner by 6 pm and fast until 2 pm the next dayRegular dietMay be challenging to meet nutrient needs if practiced daily
One Meal A Day (OMAD)Eat only one meal per day and fast for 23 hoursEat between 12 pm and 1pm each dayRegular dietMay be challenging to meet nutrient needs if practiced daily 
Alternate Day Fasting (ADF)24-hour fast every other dayFor example Monday – Fast Tuesday – Eat Wednesday – Fast Thursday – Eat  Regular dietSafe for several months, long-term challenges (1)
5:2 fasting (periodic fasting)24-hour fast 2 days per weekMonday, Tuesday – Eat Wednesday – Fast Thursday, Friday – Eat Saturday – Fast Sunday – EatRegular diet 
Fasting-Mimicking Diet (FMD)5 days of plant-based dietMay be practiced monthly for between 3 and 6 monthsPlant-based diet of 800 to 1000 calories per dayFood available through Prolon or Whole Food FMD program, available through the Hoffman Centre

With so many options, it may be challenging to determine how to start time restricted feeding or intermittent fasting. For example, do you just dive in or do you ease into it more slowly? I recommend starting with either time restricted feeding (TRF) or with the fasting-mimicking diet. (FMD). With that experience, you can then work with your provider or myself to determine if you’d benefit from other practices.

TRF may begin with a simple 12:12 schedule, meaning that you begin fasting overnight and then eat your regular diet within a twelve-hour eating window. For many people this isn’t that much different from their typical pattern, although they may have to be aware of any tendencies for late night snacking. A fast from 8 pm until breakfast at 8 am the following day is a good schedule to start with. Once you have this under your belt, you can expand your fasting window, in increments if needed, to a fourteen-hour fast with a ten-hour eating window. You can then potentially lengthen this to include a fast of sixteen hours or longer.

The fasting-mimicking diet (FMD) is a five-day program, typically practiced once per month for between three and six months, and then one time every 3-4 months as a maintenance program. During the five day fast, you follow a plant-based, calorie-restricted diet. The diet is derived from plant sources like vegetables, nuts, seeds, and fruit. The diet relies on plant foods for protein, olives, coconut and nuts and seeds for healthy fats. The diet constituents are carefully chosen by a nutritional expert. There is a commercially available program involving packaged constituents called ProLon.

With calories restricted to approximately between 750 and 1100 per day, with day one containing the most calories. This represents a réduction in calories of around 50 to 60 percent, this diet is designed to mimic molecular and cellular fasting while increasing patient compliance. The stomach sees food, while the cells see fasting. (2, 3)

The fasting mimicking diet has been clinically studied as a therapy for a variety of conditions including autoimmunity, breast cancer, and metabolic disease such as heart disease and diabetes. Extensive studies in mice have been completed, along with a few human clinical trials.

In the most recent randomized controlled trial from 2021, obese women received either a five-day fasting mimicking diet or their typical diet with a calorie deficit of 500 calories each day. This particular study didn’t indicate a difference in weight between the two groups, but the women following the fasting-mimicking plan showed reduced insulin resistance and improved appetite regulating hormones, along with preserved muscle mass and metabolic rate. (4)

At the Hoffman Centre, Justine leads a whole food fasting-mimicking program which I’ve personally undertaken three times and seen the dramatic results. An additional benefit to this structure is the group dialogue component and support provided throughout the process.

Learn more about this program here

It’s important to note that many fasting trends such as juice fasting don’t have the same benefits and may even have risks. Prolonged fasting of more than two days without food may contribute to electrolyte imbalances, dizziness, exhaustion, and other symptoms, making compliance quite challenging. Both time restricted feeding and the fasting-mimicking diet offer the benefits of fasting with intermittent fasting rules that are easy to follow.

Frequently asked questions

Let’s dive into some of the most common questions that I’m asked about intermittent fasting and time restricted eating, who it’s recommended for and who it’s not recommended for, along with some details to help you feel more confident moving forward.

Are intermittent fasting and time restricted eating safe?

Intermittent fasting and time restricted eating are safe and effective practices for many people. However, it’s important to work with your doctor, especially if you have a medical condition or take any medications. A doctor should look at your medical history, complete a physical exam, and review any laboratory testing. Please however note that your doctor may not be that familiar with these approaches to nutrition nor know the science behind it. Be sure that you are practicing the most well informed kind of patient advocacy and be prepared to educate you doctor on the subject .

While intermittent fasting and time restricted eating might be beneficial in a variety of medical cases, as explained in Part One, there are many cases in which intermittent fasting and time restricted eating are not indicated including:

  • Pregnancy and lactation
  • Anorexia, underweight, or chronic malnutrition
  • Type 1 diabetes or insulin-dependent Type 2 diabetes (as insulin requirements may plummet dramatically requiring a lowering of insulin dosing)
  • Recent stroke or heart attack
  • Pulmonary embolism or deep vein thrombosis
  • Cardiac instability or atrial fibrillation
  • Advanced kidney disease
  • Advanced liver disease
  • Advanced heart disease
  • Porphyria, MCAD
  • Inability to discontinue medications
  • Inability to obtain adequate rest while fasting
  • Active growth, such as with children or adolescents
  • Current fever, cough, or signs of an active infection (5)

Alternatively, if you’re working on any of the following imbalances or disease states, it may be worth discussing intermittent fasting and time restricted eating with your personal doctor or with myself.

  • Excess weight or obesity
  • Elevated cholesterol
  • Elevated blood pressure
  • Cardiovascular disease
  • Metabolic syndrome or type 2 diabetes
  • Lymphoma and other cancers
  • Digestive imbalance, including SIBO
  • Autoimmune disease
  • Dependency or toxicity

Fasting side effects may include fatigue, weakness, headache, dry mouth, menstrual irregularity, memory impairment, muscle pain, constipation, sugar cravings, and brain fog. Be sure to stay well hydrated and avoid strenuous exercise or extreme environments while fasting. Fasting is the ideal time for rest.

Is intermittent fasting and time restricted eating different for men and women?

While much of the initial intermittent fasting research has been conducted on animals and human men, we’re starting to learn more about the unique needs of women when it comes to fasting. Whereas men have similar hormonal patterns from day to day, women’s hormones fluctuate on a monthly cycle and then decline through perimenopause and menopause. You can learn more in my article on hormone replacement therapy.

Women seem to be more sensitive to over-fasting and restricting their food intake too much, too often. They might see imbalances in stress hormones, thyroid hormones, and sex hormones. In extreme cases, too much fasting may lead to amenorrhea or the loss of a woman’s period, especially when percentage body fat drops below a certain percentage. When it comes to intermittent fasting for women, it’s important to note that more fasting isn’t always better. A less-is-more-approach often applies.

And while each woman is different, it’s challenging to provide advice for fasting in women on a worldwide basis. For example, some women with autoimmune disease do very well with implementing intermittent fasting practices, while others might do more poorly. Remember that fasting is a stressor on the body and this can be a good stressor that leads to autophagy, detoxification, and cellular rejuvenation. Yet if the system is already stressed, fasting can sometimes be the straw that breaks the camel’s back. Often, if a woman is exhausted, overwhelmed, and feeling burnt out this isn’t the time to add even more stress.

In a study of obese women, intermittent fasting combined with calorie restriction was shown to reduce weight over a ten-week period. (6) However, many restrictive methods work in the short-term and we may need to learn more about the long-term results of fasting for women.

In another study comparing men and women in a forty-eight-hour fast, it was noted that women tend to accumulate triglycerides in their muscles, while men accumulate these in their livers, although other physiological aspects during the fast were similar. (7) We certainly need more research to further establish the differences related to long-term fasting practices and the different types of intermittent fasting between men and women regarding the potential benefits fasting.

As always with functional medicine, a personalized approach is best. As discussed above, I recommend starting with gentle time restricted feeding or with the fasting-mimicking diet.

Can I drink coffee or tea during fasting hours?

This question about hot drinks usually leads to hot debate! Whether you can drink coffee while intermittent fasting may depend on what works best for you as an individual.

Experts in the fasting field recommend “complete abstinence from all substances except pure water.” (5) Biological fasting is the absence of anything that triggers nutrient-sensing pathways. (3) This certainly means no protein, carbohydrates, or fats, but most likely no vitamins, minerals, or plant compounds either.

While black coffee or tea, doesn’t contain any calories, it does contain caffeine, which can influence the hormones cortisol and insulin. It also contains phytonutrients, the antioxidant compounds that are absorbed and which rely on digestion and metabolism.

So, what can you drink during intermittent fasting? If you want to be a purist, stick to only water during your fasting window then enjoy coffee or tea with your first meal of the day or at any time within your eating window.

After that, you can experiment with plain coffee or tea within your fasting window and see whether it improves, or deters from, your results. Coffee or tea with added fat, such as bulletproof coffee, should be enjoyed during the eating window.

Does intermittent fasting and time restricted eating help with weight loss?

Weight loss is difficult and traditional strategies are largely based on reducing calories and increasing exercise. However, these strategies, especially extreme versions, typically only produce short-term results. Many factors contribute to weight, including hormones, sleep, stress, nutrient levels, toxin exposure, mindset, and so much more. Simply looking at calories doesn’t always address the situation and a short-lived fast may only result in a Band-Aid effect. Yet for some, even a quick boost in hope and confidence that the body can lose stubborn weight can be a catalyst for deeper change. That’s why discussing how to use fasting with a trained professional is key.

Using intermittent fasting and time restricted eating for weight loss might be a solution, or just part of the weight solution, especially for someone who spends the majority of their time in the fed state. Fasting might provide the metabolic balance that will address some of the underlying physiology contributing to weight gain, such as inflammation, elevated insulin, and oxidative stress.

In a review of different types of intermittent fasting, IF produced similar weight loss results to those derived from caloric restriction. 5:2 fasting was similar to restricting daily calories in nine out of eleven studies. In addition, the majority of the weight loss occurred in the first three months before weight hit a plateau and results were similar with different distributions of macronutrients. Time restricted feeding and caloric restriction also seemed similar as far as weight was concerned. (8)

In a long-term study that compared alternate day fasting or ADF with daily calorie restriction in obese adults, weight loss after one year was 6 percent in the ADF group compared to 5.3 percent in the calorie restriction group, so there wasn’t a huge difference. (9)

When examining human studies involving individuals with diabetes, those practicing time restricted feeding as opposed to consuming six small meals per day lost more weight. The studies also showed more results with intermittent fasting in terms of decreasing A1C and blood glucose, which are markers of diabetes, compared to a common recommendation of eating frequent small meals. (10)

The definitive answer to this question regarding the intermittent fasting weight loss diet may not be clear in the science. However, I’ve seen it used successfully in my practice for patients who are good candidates, along with other functional medicine interventions.

Does intermittent fasting and time restricted eating work while following a ketogenic diet?

Ketogenic diets, time restricted eating, and intermittent fasting are often discussed as going hand in hand. Keto, which is an abbreviation for the ketogenic diet, is a high fat, low carbohydrate eating pattern that in its own way mimics the fasting state through the restriction of dietary glucose. The ketogenic diet, time restricted eating, and intermittent fasting all have the potential to increase ketones in the blood that can be used as fuel by the cells instead of them employing glucose. The ketogenic diet combined with time restricted eating and intermittent fasting may also have similar benefits related to a treatment approach to chronic and metabolic diseases.

To answer the question, yes, intermittent fasting and time restricted eating can be combined with a ketogenic diet. Those following a ketogenic diet that are in a state of ketosis, where the body is efficient at turning fat into ketones and using them as fuel, may have a better experience with fasting and fewer negative side effects. Similarly, those with an existing fasting practice might have an easier time transitioning to a ketogenic diet because their metabolism is already primed to use ketones.

So, while intermittent fasting or time restricted eating combined with a keto diet may certainly be an important dietary approach for some people healing from chronic disease or working to promote longevity, it may be too restrictive for others. This is another reason why working with an experienced practitioner can be so helpful. You can dial in your nutrition plan and then have support adjusting, and even expanding, the diet over time.

We all want to remain healthy and high-functioning as we get older, but it’s about more than living a long time. It’s about improving our quality of life. Intermittent fasting is meant to mimic the balance between feast and famine that humans have always experienced throughout history. Regular feasting is a relatively recent development and this excess time in the fed state may deter us from experiencing all of the important health and longevity benefits that come from fasting. The best part about intermittent fasting is that it makes fasting simple, gentle, and fit into modern life.

To learn more about working with me individually or to join our next group fasting-mimicking diet, please contact my office.

References:

  1. Stekovic S, Hofer SJ, Tripolt N, et al. Alternate Day Fasting Improves Physiological and Molecular Markers of Aging in Healthy, Non-obese Humans [published correction appears in Cell Metab. 2020 Apr 7;31(4):878-881]. Cell Metab. 2019;30(3):462-476.e6.
  2. Di Francesco, A., Di Germanio, C., Bernier, M., de Cabo, R. A time to fast. Science. 2018;362(6416),770-775.
  3. Hong, K. Intermittent Fasting and Fasting Mimicking: Clinical Applications. Presentation. University of Southern California.
  4. Sadeghian M, Hosseini SA, Zare Javid A, Ahmadi Angali K, Mashkournia A. Effect of Fasting-Mimicking Diet or Continuous Energy Restriction on Weight Loss, Body Composition, and Appetite-Regulating Hormones Among Metabolically Healthy Women with Obesity: a Randomized Controlled, Parallel Trial [published online ahead of print, 2021 Jan 9]. Obes Surg. 2021;10.1007/s11695-020-05202-y.
  5. Goldhamer, A. Can Fasting Save Your life. TrueNorth Health Center.
  6. Klempel MC, Kroeger CM, Bhutani S, Trepanowski JF, Varady KA. Intermittent fasting combined with calorie restriction is effective for weight loss and cardio-protection in obese women. Nutr J. 2012;11:98. Published 2012 Nov 21.
  7. Browning JD, Baxter J, Satapati S, Burgess SC. The effect of short-term fasting on liver and skeletal muscle lipid, glucose, and energy metabolism in healthy women and men. J Lipid Res. 2012;53(3):577-586.
  8. Rynders CA, Thomas EA, Zaman A, Pan Z, Catenacci VA, Melanson EL. Effectiveness of Intermittent Fasting and Time-Restricted Feeding Compared to Continuous Energy Restriction for Weight Loss. Nutrients. 2019;11(10):2442. Published 2019 Oct 14.
  9. Trepanowski JF, Kroeger CM, Barnosky A, et al. Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial. JAMA Intern Med. 2017;177(7):930-938. doi:10.1001/jamainternmed.2017.0936
  10. Muñoz-Hernández L, Márquez-López Z, Mehta R, Aguilar-Salinas CA. Intermittent Fasting as Part of the Management for T2DM: from Animal Models to Human Clinical Studies. Curr Diab Rep. 2020;20(4):13. Published 2020 Mar 12.

How Does Time Restricted Eating and Intermittent Fasting Work? Part I

How Does Time Restricted Eating and Intermittent Fasting Work? Part I

If you’re interested in living a healthier lifestyle, you’ve probably heard of time restricted eating, or intermittent fasting and the success stories associated with incorporating these practices into your life. Despite living longer these days, the healthspan of many Americans is actually cut short as the average person spends seventeen of their final years living in poor health. This is due to chronic diseases such as diabetes, heart disease, cancer, and Alzheimer’s. In fact, 80 percent of older adults have at least one chronic condition, which is primarily related to their lifestyle.

What if time restricted eating or intermittent fasting could be a solution, one of the tools in the kit, to help combat the underlying factors that contribute to such diseases? Is time restricted eating and intermittent fasting simply a diet trend? Or is there a substantial and credible scientific basis to warrant its therapeutic use?

In this two-part series, we’ll explore these questions, and more.

In Part One we’ll examine the nature of time restricted eating and intermittent fasting, how it works, and the health benefits of both practices.

Part Two will cover methods of fasting and time restricted eating, along with answers to the most commonly asked questions regarding this popular practice.

What are time restricted eating and intermittent fasting?

Time restricted eating, (TRF) and intermittent fasting, also referred to as IF, are often treated as if they are one and the same, but there are actually some major differences between the two.

Time restricted eating involves simply alternating periods of eating with periods of fasting. With TRF, all of your eating is compressed into a 1 -12 hour feeding window. Most hours of the waking day, you’ll spend in a feeding state—say from 8:00 am to 4:00 pm. The other hours, you don’t consume any calories, although you are allowed calorie-less drinks, like water, sparkling water, decaffeinated tea and black coffee. Some people, (known as OMAD’s), eat only one meal a day (OMAD) and fast for 23 hours. 

The term intermittent fasting can be confusing and inaccurate. The term ruffles some researchers feathers because there are many different forms of fasting or restriction. It’s important to distinguish between them. The other problem with the term intermittent fasting is the flexibility around the term “fasting.” Most studies on various intermittent fasting schedules allow up to 700 calories per day on fasting days, while others don’t allow any calories. I want to be very particular about the definitions because I think different forms of fasting and different types of restriction may have different physiologic effects, and by lumping all forms of fasting together, we may dilute such insights.

Intermittent fasting includes the fasting-mimicking diet or FMD, where your intake is restricted to between 750 and 1050 calories (approximately) per day for a five-day period out of the month. This has been shown to mimic some of the physiological benefits of water fasting.

In addition, intermittent fasting also includes alternate day fasting or ADF. With this type of fasting a regular diet is followed for one day followed by a day of fasting. Another option is 5:2, which involves five days of regular eating followed by two fasting days in one week. With each of these methods, the fasting days can feature either a water fast or a calorie-reduced diet.

In contrast, a long-term or prolonged fast is considered more than two days and up to several weeks without food.

As you can see, there are several versions of intermittent fasting in which individuals can engage and that have been explored with scientific research. I’ll cover these in more detail when we discuss an intermittent fasting schedule and how to implement it in Part Two of this series.

How intermittent fasting works

If we take a look back in time to more ancestral or hunter-gatherer ways of eating, feasting was always balanced with famine. There were naturally times of the year when food was abundant and times of the year when food was scarce. The human body has the ability to adapt and thrive in both cases.

With the onset of our modern agricultural system, most of us in the developed world no longer have natural periods of fasting and life is a perpetual feast. We have access to whatever food we desire, grown anywhere in the world, every day. It’s no wonder that rates of obesity are the highest they’ve ever been, leading to inflammation and chronic disease. These days the body’s systems never have an opportunity to rest and reset.

So how exactly does intermittent fasting work? To answer this question, we need to go behind the scenes and into the cell to understand what’s happening on the cellular level, in both the fed state and the fasting state.

When we eat a meal, the body’s system is dedicated to processing food, which places the cell in growth mode. Insulin levels are higher, signaling the cell to grow. More specifically, insulin signals mTOR, meaning mammalian target of rapamycin, which instructs the cell to grow and divide. mTOR also decreases autophagy, the process of cellular recycling, that’s predominant during fasting and important for regular repair and maintenance of the cell. (1)

Autophagy naturally declines with age and decreased autophagy is related to neurodegenerative disease, cardiomyopathy, cancer, metabolic syndrome, suppressed immunity, and signs of aging. Boosting autophagy by means of intermittent fasting methods may help to slow or reverse these changes.

In the fasting state AMPK, or 5’ AMP-activated protein kinase, slows down mTOR. This causes fat breakdown and works to activate autophagy, allowing the body to run on its own stored fuel in the form of fat. AMPK also cleans up and repairs parts of the cell that don’t work, an important process that contributes to healthy aging and preventing diseases such as cancer. (1)

In addition, fasting, intermittent fasting, and calorie restriction down regulates IGF-1, or insulin-like growth factor-1. IGF-1 signaling is important for protein synthesis, as well as blood sugar regulation and growth. Later in life, increased IGF-1 can accelerate the aging process and decreasing it, through methods such as IF or time restricted eating, may increase longevity. Studies in mice indicate that employing different types of intermittent fasting can result in an increased lifespan. (1)

When food is scarce, the body conserves energy by downregulating or decreasing both mTOR and IGF-1, which increases stress resilience and protection on the cellular level. In fact, this can be considered inner rejuvenation, which reduces inflammation and increases autophagy. The results include increased stem cell regeneration and improved immunity, especially during fasts lasting more than a few days or by means of fasting-mimicking. (1)

Decreasing IGF-1 also decreases cellular senescence, in which the cell loses its ability to divide, as measured by telomere length. This process of cellular senescence is caused by underlying factors that produce oxidative stress, changes in the epigenetic gene expression, metabolic dysfunction, and mitochondrial dysfunction and the process is considered irreversible. However, decreasing IGF-1 or mTOR increases sirtuins, via the antiaging molecule NAD+, autophagy, and enables DNA repair. (1)

When the body is in a fed state, cells are highly acetylated so that genes are turned on. This helps cells to survive and proliferate. When these genes are on, the ones that are more related to fat metabolism, stress resistance, and cellular repair are turned down. (1)

This is what happens metabolically throughout a longer fast or a fast-mimicking diet over the course of five days.

  • 12 hours: The body transitions from primarily using glucose as fuel to increasing ketones as the preferred fuel for cells, including cells in the brain. (2) This causes an increase in BDNF, or brain-derived neurotropic factor, which allows for increased brain plasticity and neurogenesis. (1)
  • 18 hours: Ketone levels continue to rise. More ketones lead to a decreased need for glucose and insulin, along with more BDNF.
  • 24 hours: Cells increase autophagy, allowing for recycling and the breakdown of old or broken cellular components. (3)
  • 48 hours: Growth hormone (GH) is five times higher than normal, helping to preserve lean muscle mass, reduce fat, and is important for longevity. (4)
  • 54-72 hours: Insulin sensitivity increases and new stem cells and immune cells form. (5)

In summary, on the cellular level, fasting results in the following:

  • Decreased mTOR
  • Reduced IGF-1
  • Increased AMPK
  • Increased autophagy
  • Greater NAD+ and sirtuins
  • Increased ketones
  • Increased BDNF
  • Increased GH
  • Reduced levels of insulin and blood glucose
  • Decreased cellular senescence
  • Increased fat metabolism
  • Improved resistance to cellular stress
  • Reduced inflammation

Our bodies still need both the fed and fasting state, but in our modern culture the balance strongly favors always being fed. Intentional fasting may be a way to add greater balance to the system by allowing for these natural cellular processes that primarily happen in the fasted state.

Health Benefits of Intermittent Fasting and Time Restrictive Eating

Now that we’ve covered the science of fasting and time restricted eating, the question I’m often asked is whether these practices work in regard to health and longevity. This is an exciting area of study, using a wide variety of animal models, along with increasing numbers of studies in humans, in order to decipher the potential benefits of intermittent fasting and implementing time restricted eating.

Research has indicated a number of positive clinical benefits related to intermittent fasting and time restricted eating

  • Weight loss
  • Changes in body composition/fat loss
  • Improved insulin sensitivity or decreased insulin resistance
  • Reduced oxidative stress
  • Increased cellular autophagy
  • Stem cell regeneration
  • Optimized neurogenesis
  • Enhanced parasympathetic nervous system response
  • Improved gut motility, which is important for conditions like SIBO
  • Reduced heart rate
  • Reduced blood pressure
  • Improved lipid/cholesterol balance
  • Improved cognitive function
  • Improved detoxification
  • Improved physical performance
  • Improved sleep patterns
  • Improved immunity (1,6,7)

Taken together, all these clinical benefits translate into important applications related to longevity and chronic disease reversal. Intermittent fasting results are clearly beneficial for a variety of disease states and populations, including those with cardiovascular disease, diabetes, obesity, dementia, cancer, depression, and a number of other conditions. (6,7)

Intermittent fasting addresses the metabolic root causes that contribute to disease over time. IF and time restricted eating may be an important lifestyle tool, along with diet, physical activity, and stress reduction, that brings health more into balance.

In Part Two of this series on intermittent fasting, we explore the specifics of the different types of intermittent fasting, along with how to implement an intermittent fasting schedule. We’ll then cover some frequently asked questions on the topic and provide details and guidance to get you started.

If you’re looking for more personalized guidance, or are interested in our whole food fasting-mimicking program available through Justine Stenger and the Hoffman Centre for Integrative and Functional Medicine, please contact us for more information.

References:

  1. Hong, K. Intermittent Fasting and Fasting Mimicking: Science and Molecular Mechanisms. Presentation. University of Southern California.
  2. Anton SD, Moehl K, Donahoo WT, et al. Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting. Obesity (Silver Spring). 2018;26(2):254-268.
  3. Alirezaei M, Kemball CC, Flynn CT, Wood MR, Whitton JL, Kiosses WB. Short-term fasting induces profound neuronal autophagy. Autophagy. 2010;6(6):702-710.
  4. Hartman ML, Veldhuis JD, Johnson ML, et al. Augmented growth hormone (GH) secretory burst frequency and amplitude mediate enhanced GH secretion during a two-day fast in normal men. J Clin Endocrinol Metab. 1992;74(4):757-765.
  5. Klein S, Sakurai Y, Romijn JA, Carroll RM. Progressive alterations in lipid and glucose metabolism during short-term fasting in young adult men. Am J Physiol. 1993;265(5 Pt 1):E801-E806.
  6. Hong, K. Intermittent Fasting and Fasting Mimicking: Clinical Applications. Presentation. University of Southern California.
  7. Goldhamer, A. Can Fasting Save Your life. TrueNorth Health Center.
  8. Rynders CA, Thomas EA, Zaman A, Pan Z, Catenacci VA, Melanson EL. Effectiveness of Intermittent Fasting and Time-Restricted Feeding Compared to Continuous Energy Restriction for Weight Loss. Nutrients. 2019;11(10):2442. Published 2019 Oct 14.

Health Benefits of NAD+ Supplements

Health Benefits of NAD+ Supplements

NAD+ is a molecule that’s found in every cell of your body that plays many key roles in energy production, health, and longevity. Exciting research has uncovered why NAD+ is so essential and has led to many clinical applications, addressing everything from the signs and symptoms of aging to treating and preventing chronic disease.

In this article, you’ll learn more about:

  • What NAD supplement is
  • The two forms of NAD, namely NAD+ and NADH
  • The role NAD+ plays in health and disease
  • Why increasing levels of NAD+ is important
  • What sirtuins are and how they require NAD+
  • The role sirtuins and NAD+ play in vascular aging
  • Health conditions that benefit from increasing NAD+
  • The three ways the body produces NAD+
  • Natural ways to increase NAD+ levels in the body

What is NAD+?

A fair amount of attention has been given to NAD+, particularly for its ability to slow down the effects of aging. NAD+ stands for nicotinamide adenine dinucleotide and it’s used as a coenzyme in many molecular processes that keep your cells and body alive. A coenzyme is like an enzyme helper or assistant and needs to be available for the reaction to take place.

Adequate intracellular NAD+ levels don’t just prevent hastening of cellular aging. They also help to prevent the visible signs of aging that become apparent on the skin. The use of NAD treatment for addiction relies on the speedy delivery of NAD IV therapy and there are numerous NAD+ addiction clinics operational in the United States.

The NAD+ molecule is found in every cell in the body, enabling the conversion of food we eat into energy and chemical products that the body needs to sustain itself. This is very important, since the health and function of every cell relies on this tiny molecule.

NAD+ also plays a critical role with enzymes that regulate gene expression involved in the repair of damaged DNA. Through these pathways, NAD+ influences a variety of processes involved in every cell in your body, improving mitochondrial efficiency, enhancing cell viability, down-regulating inflammation, increasing the antioxidant capacity of cells and tissues, and activating SIRT1, a sirtuin enzyme that plays a role in longevity.

NAD+ and NADH are two different forms of the same molecule, picking up and dropping off electrons. This energy exchange of electrons is what allows the Krebs cycle and electron transport chain to produce ATP, the energy currency in humans. When it picks up an electron, this is NADH, while without the electron it is known as NAD+.

The role of NAD+ in health and disease

Several of these critical roles have already been mentioned, but let’s take a closer look at some of the life-sustaining benefits of NAD+ .

NAD+ is a cofactor for hundreds of enzymatic reactions, such as chromosomal stability and DNA repair. DNA damage is linked to deteriorating chronic health problems, as recently discussed by Robert Naviaux and his theory of the Cell Danger Response.

NAD+ also plays a vital role in energy production, in the Krebs cycle conversion of macronutrients including protein, fats and carbohydrates, and micronutrients such as vitamins and minerals, to ATP. This is the energy molecule that’s crucial to the running of all the body’s essential functions.

In addition, NAD+ is also a cofactor for hundreds of similar enzymatic reactions that are involved in:

  • Immune cell signaling and immune strengthening
  • Decreasing inflammation
  • Decreasing oxidative stress and ‘rusting’ of cells
  • Telomere production, with longevity enhanced by longer telomeres
  • Neurotransmitter production
  • A healthy circadian rhythm and sleep cycle
  • Increased activity of sirtuins, which play a role in longevity (see more on this below)
  • Prevention of blood vessel damage that reduces the risk of heart disease
  • Healthy aging

The importance of increasing levels of NAD+

NAD+ plays a central role in every one of the body’s functions. We simply can’t do without it. In addition, if we boost its levels, we can further optimise cell functions and energy outcome. Unfortunately, as we age levels of NAD+ decline, leading to signs and symptoms of aging.

Low levels of NAD+ are associated with:

  • Accelerated aging
  • Increased sunburn and skin cancer
  • Decreased cellular antioxidants
  • Decreased metabolism along with thyroid hormones
  • Harmed immune function
  • Increased inflammation
  • Impaired brain function
  • Hypoxia (low levels of oxygen) intracellularly

When NAD+ levels are higher and more robust, we see the following:

  • Improved mitochondrial health
  • Improved cellular metabolism and energy production
  • Improved production of sirtuins
  • More NAD anti-aging benefits
  • Improved DNA repair and recovery
  • Increased immunity, with NAD+ stimulating CD38 that’s present on T-cell immune cells, effectively boosting the immune response
  • Stimulation of CD38 activity increasing oxytocin, a hormone associated with social intimacy and bonding
  • Increased autophagy or cellular recycling
  • Increased redox potential, with more antioxidant action protecting cells
  • Improved insulin sensitivity, decreasing the risk of metabolic syndrome and diabetes
  • Improved protection of brain cells from oxidative stress, rescuing neuronal loss and improving myelination
  • Improved skin health by boosting levels of collagen, keratin, elastin, and hyaluronic acid, a compound found in many skin rejuvenating creams
  • Increased stem cells
  • Improved exercise performance

NAD+ provides these benefits through several key mechanisms, including:

  • Promoting AMPK activity, an enzyme that improves metabolism and helps protect against obesity and diabetes.
  • Modulating p53, a tumor suppressor gene that repairs damaged DNA and protects against cancer initiation
  • Inhibiting NF-kB or nuclear factor-kappa B, a protein that induces the chronic inflammation tied to many diseases and premature aging
  • Inhibiting mTOR, a molecular complex whose abnormal activation contributes to many chronic diseases of aging

Sirtuins and NAD

Sirtuin is an acronym for ‘silent information regulator’. This refers to any family of enzymes, made up of proteins, that occur in all living organisms. They’re thought to regulate a wide array of cellular processes such as cellular aging, apoptosis, and stress resistance in more complex organisms. It’s been demonstrated that increasing sirtuin activity leads to longer life and reduction in age-related loss of function. It also protects against DNA damage. NAD levels decline with aging, which also results in reduced sirtuin activity. Boosting NAD+ helps to ramp up this activity.

Seven sirtuins have been identified and play different roles in the body.

  • Sirtuin 1 (SIRT1) repairs DNA and vascular tissue and is highly dependent on NAD+ levels
  • Sirtuin 2 (SIRT2) reduces body fat and oxidative stress
  • Sirtuin 3 (SIRT3) influences longevity
  • Sirtuin 4 (SIRT4) can repress tumors and autophagy
  • Sirtuin 5 (SIRT5) reduces fatty acids in the liver and oxidative stress
  • Sirtuin 6 (SIRT6) regulates blood sugar and decreases insulin resistance
  • Sirtuin 7 (SIRT7) benefits the heart

NAD+, sirtuins, and vascular aging

As we age, our small blood vessels die off. This compromises blood flow and the oxygenation of organs and tissues that are fed by these small vessels. Vascular aging is responsible for a constellation of disorders, such as cardiac and neurological conditions, muscle loss, impaired wound healing, and overall frailty.

Dr. David Sinclair, a researcher at the Department of Genetics at Harvard Medical School and a co-director of the Paul F. Glenn Center for the Biology of Aging at Harvard Medical School, has discovered a way to reverse vascular aging by boosting the presence of naturally occurring molecules in the body that augment the physiological response to exercise. He states that, “The approach stimulates blood vessel growth and boosts stamina endurance in mice and sets the stage for therapies in humans to address the spectrum of diseases that arise from vascular aging.”

Dr. Sinclair’s study revealed that NAD+ and SIRT1 enable the conversation between endothelial cells in the walls of blood vessels and muscles, but specifically the cells in young mouse muscles, activating SIRT1 signaling generating new capillaries that supply oxygen and nutrients to tissues and organs. Conversely, the study demonstrated that as NAD+/SIRT1 activity diminished over time so did blood flow, which left muscle tissue deprived of nutrients and starved of oxygen.

Dr. Sinclair gave an NAD supplement, as an NAD+ precursor, for two months to a group of mice that were twenty months old, roughly equivalent to seventy in human years, to test its effect on SIRT1 signaling. The treatment worked and restored the number of blood capillaries and capillary density to those seen in younger mice. Blood flow to the muscles also increased and was more significantly higher than blood supply to the muscle seen in mice of the same age that didn’t receive the NAD+ precursor.

The most striking effect emerged in the aging mice’s ability to exercise. These animals showed a 56 to 80 percent greater exercise capacity when compared to that of untreated mice. It was concluded that this observation underscored the notion that age plays a critical role in the crosstalk between blood vessels and muscles. This points to a loss of NAD+ and SIRT1 as the reason behind the reduction in exercise effectiveness after middle age. The researchers believe that their findings might pave the way to therapeutic advances that might be able to help the millions of older people for whom regular physical activity is no longer an option.

“Even if you’re an athlete you eventually decline,” Sinclair says. “But there is another category of people – what about those who are in a wheelchair or those with otherwise reduced mobility?”

Dr. Sinclair’s mouse study suggests that NAD+ may support exercise performance in humans. In a study involving elderly men, supplementation with an NAD+ precursor resulted in improved exercise performance. The men had an 8 percent improvement in peak isometric muscle torque, which is a measure of muscle force, and a 15 percent improvement in lessening of fatigue associated with exercise.

Health conditions that benefit from increased NAD+

Considering what we’ve explored regarding NAD+ energy production in every cell and the importance of this molecule in all aspects of health and longevity, it’s no surprise that NAD+ may benefit a number of health conditions, including chronic disease. Conditions that may benefit from increased levels of NAD+ in the cells include:

  • Addiction
  • Allergies
  • Neurological deficits
  • Depression
  • Brain injury
  • Cholesterol metabolism issues
  • Cancer
  • Chronic fatigue syndrome
  • Fibromyalgia
  • Irritable bowel syndrome (IBS)
  • Diabesity spectrum, including obesity, metabolic syndrome, and Type 2 diabetes
  • Systemic inflammation
  • Lyme disease
  • Malabsorption syndromes
  • Parkinson’s disease
  • Alzheimer’s disease
  • Huntington’s disease
  • ALS
  • PTSD
  • Autism spectrum
  • Small bowel overgrowth syndrome (SIBO)
  • Cardiovascular disease
  • Multiple sclerosis
  • Hearing loss
  • Renal disease

NAD+ pathways of production

There are three major pathways that our body employs to synthesize in NAD+. Influencing and activating these pathways are a way to increase NAD+ within the cells of the body.

The first pathway is the de nova synthesis from the amino acid tryptophan from food protein sources, which also intersects with vitamin B3. This is the long way round.

The second is a salvage pathway, used by the supplement company PRICERA, that our body uses daily to recycle nicotinamide (NAM) according to circadian rhythms. This is the dominant and most robust path for any NAD+ synthesis.

The third pathway is specialized for nicotinamide riboside (NR) reactivation. NR is a shunt product in NAD+ synthesis.

The supplement company claims that PRICERA is the only available compound that utilizes the naturally dominant pathway to generate NAD+ efficiently and robustly. This product is said to improve the tissue distribution of NAD+, maintain and enhance mitochondrial health and creation, and plays a key role in calorie restriction for increased lifespan and exercise response. PRICERA is also said to prevent neurodegeneration and reduce age-related cognitive decline. In addition, it’s claimed that PRICERA increases ATP and maintains antioxidant levels including glutathione, which generally becomes depleted with higher energy requirements or when we’re under stress.

PRICERA differs from other NAD precursor products in that it includes D-ribose, a known source of energy for the mitochondria in the heart, brain, and muscles. Other NAD precursor products need ATP to prime the pathway. However, since PRICERA spares the body’s own energy, one of its key applications may be to serve individuals with compromised mitochondrial function. This can actually hamper performance under oxidative stress.

How To Raise NAD+ Naturally

Fasting, calorie restriction, exercise, and NAD boosters increase the intracellular levels of NAD+, activate SIRT1, and have other physiological benefits. There are a number of ways to boost your NAD+ levels naturally through lifestyle change, diet, and supplementation.

When we exercise, we use up NAD+ and replenish it rapidly. As a result exercise can help us to build up our reserves.

When we burn fat for energy instead of carbohydrates, we preserve adequate levels of NAD+ and increase levels of NAD+ in the brain. This reduces DNA damage in the hippocampus, which is the location of memory storage. Ketosis is achieved by following a ketogenic diet. In addition, ketosis might be enhanced for part of the day through practices such as intermittent fasting, fasting mimicking, or periodic longer fasts. Calorie restriction and intermittent fasting will also increase NAD+ levels.

Vitamin B3 or niacin supplements, along with foods rich in vitamin B3, such as green vegetables, chicken, portabella mushrooms, rice, nuts, tuna, although you need to be careful of mercury, will benefit the body’s NAD+ production. Niacin is believed to act as a building block for NAD+ levels. Lycopene-rich foods, such as tomatoes, also help to prevent NAD+ depletion.

You can take a NAD+ supplement orally or apply it to your skin. When taking an oral preparation you have to take a precursor molecule, as NAD+ will break down in your gut without being absorbed. Nicotinamide riboside (NR) is this type of NAD+ precursor.

NAD IV may be an option for individuals with certain conditions such as addiction, who have access to this type of therapy. NAD+ bypasses the gut and is delivered directly to the bloodstream, where it can enter cells.

NAD repletion strategies, such as those outlined above, have shown therapeutic potential as a means to restore a healthy metabolism and physiological function. Many health conditions are multifactorial and require a root cause approach. Bearing in mind the robust and expanding research on NAD+ I’m often considering NAD+ depletion as a factor in patient’s cases, working with them to restore these pathways and reap all of the physiological and anti-aging benefits.

To work together one-on-one, please contact my office for an appointment.