Intermittent Fasting & Immune System Rejuvenation

Jul 24, 2023 | ANJC News & Updates

The following article is excerpted and adapted from Dr. Rob Silverman’s new book, Immune Reboot: Your Guide to Maximizing Immunity, Restoring Gut Health, and Optimizing Vitality.

When the body is dealing with chronic disease or low-level systemic inflammation, the immune system becomes dysregulated. It becomes imbalanced and clogged with old white blood cells that aren’t functioning well.

In this situation, boosting the immune system may not be the best strategy for restoring health. The use of immune-boosting supplements to amplify certain aspects of an immune system that is already imbalanced and over-extended will only perpetuate the dysfunction.

Rather than boosting the system, a better goal is to reset and rejuvenate it, and to replace worn-out immune cells with new ones to improve immune resilience. At the same time, however, the immune system must have sufficient micronutrients to support the growth of healthy new immune cells.

Fasting and Autophagy

Fasting is a well-known method for stimulating the removal of old immune cells, producing new ones, and resetting the immune system. Fasting triggers the process called autophagy—a breakdown and removal of damaged or dysfunctional white blood cells, including those misdirected against the body’s own tissue (autoimmunity). Autophagy is particularly effective in destroying immunosenescent cells responsible for altering immune functions due to aging.

Intermittent fasting—a meal schedule that alternates between normal eating patterns and brief but frequent full fasts (or restricted caloric intake)—is an effective method for increasing the rate of autophagy. There are several different approaches to this, including alternate-day fasting and daily time-restricted eating.

Regardless of the method chosen, the principle is similar. During periods of calorie restriction, the body removes senescent leukocytes and replaces them with newly generated cells, reducing the overall inflammation in the body.

Eating again following a brief fast will stimulate stem cells to generate new leukocytes, a discovery for which Japanese cell biologist, Yoshinori Ohsumi, won the 2016 Nobel Prize in physiology or medicine.

Within cells, a similar process of removal and replacement occurs with the mitochondria. At that level, fasting triggers a different type of autophagy called mitophagy, where old, damaged, dysfunctional mitochondria are broken down and removed, allowing the remaining mitochondria to function better. At the same time, mitophagy helps reduce the production of undesirable inflammatory cytokines from the cell.

Intermittent Fasting Basics

Intermittent fasting (IF) can take several forms. Which works best for an individual is a matter of personal preference. Some people follow alternate-day fasting, a cycle of fasting on one day, and eating normally on the next. Others prefer the 5:2 approach, with five days per week of unrestricted eating and two non-consecutive days of eating only one small meal (500 to 700 calories). The fasting-mimicking diet (FMD), pioneered by Valter Longo, Ph.D., is a periodic, multi-day diet that restricts calories but is high in unsaturated fats and nutrients, mimicking the fasting state.

For most people, time-restricted eating (TRE) is a more manageable way to follow an intermittent fasting eating pattern. One common approach is limiting eating to a relatively short daytime window after fasting for at least 12 hours overnight. In my experience, aiming for a 14:10 eating pattern works well for many people. This means fasting for 14 hours between the evening meal and the first meal the next day. This pattern allows for three meals daily and isn’t unduly disruptive of daily routines.

After fasting overnight, unsweetened clear liquids such as water, tea, herbal tea, and black coffee are acceptable and encouraged. Drinking plenty of these liquids keep you hydrated and helps replace snacks in the evening hours. In addition, coffee and green tea are excellent sources of antioxidant compounds that support immunity.

During the 10-hour eating window, I advise my patients to follow a health-oriented, plant-forward diet. There’s no need to reduce or count calories or fat grams during the eating window. Eat your normal healthy diet in your usual portions. The reality is that most Americans eat half or more of their daily calories by snacking on low-nutrient ultra-processed foods (aka junk food) after dinner. Time-restricted eating means fasting for 14 hours or longer after the evening meal, which helps avoid this very damaging and highly inflammatory eating pattern.

Daily intermittent fasting also enhances mitophagy and improves mitochondrial function. The mechanisms behind this are still being explored. We know, however, that the process involves several transcription factors that promote mitochondrial biogenesis. One example is nuclear factor 2 (NRF2), which regulates the mitochondrial production of reactive oxygen species. Fasting may enhance the production of NRF2 and improve the expression of antioxidant regulatory genes.

A Role for Spermidine

The value of intermittent fasting for immune rejuvenation through autophagy may be enhanced by supplementing with spermidine–a polyamine that induces autophagy through the TOR kinase pathway. Spermidine mimics the action of caloric restriction on the body.

While not a substitute for intermittent fasting, spermidine supplements are particularly valuable for maintaining the rejuvenation effect during times when fasting periods must be shorter than usual. This is particularly helpful for keeping you on track when your schedule is disrupted by travel, work, illness, or other unpredictable aspects of daily life.

Improving Metabolism

Being overweight or obese has a multitude of negative impacts on immunity. Adipocytes (fat cells) secrete many chemical messengers, including leptin (the satiety hormone) and adiponectin (a cytokine linked to insulin resistance). In overweight and obese people, leptin secretion increases and induces the production of pro-inflammatory cytokines, including TNF-alpha, IL-6, IL-8, and IL-12. Adiponectin production is reduced, leading to the inhibition of phagocytic activity in macrophages and neutrophils. Adipose tissue also releases the inflammatory cytokines TNF-alpha, IL-6, and IL-8. About 30 percent of circulating IL-6 is generated by adipose tissue.

Excess adipose tissue causes people who are overweight or obese to have chronic low-level inflammation and reduced immune response. Regardless of age, they are at increased risk of infection and a worse disease outcome, increasing mortality risk. During flu epidemics, for example, people who are overweight or obese are more likely to get sick, remain sick for longer durations, and continue shedding the virus for longer — all indicators of impaired immunity. Overweight or obese people, especially if they also have diabetes, are much more likely to need hospitalization for COVID-19.

Time-restricted eating, even without cutting calories, can reduce body weight, inflammation, hypertension, and high cholesterol. Many people find that intermittent fasting helps them lose weight by losing body fat, not muscle. In addition, it also reduces inflammation and improves insulin sensitivity.

In a recent study, a 3-month IF diet intervention among 36 people with diabetes who used drugs to lower blood sugar or used insulin found that 90 percent of them were able to reduce their intake of drugs after intermittent fasting. The IF effect was so powerful that 55 percent of these patients experienced diabetes remission, discontinued their diabetes medications, and maintained normal blood sugar levels for at least a year.

By not adding to their blood sugar during the fasting period, people with diabetes can activate their bodies’ ability to use existing blood sugar for energy, so there’s little left over to be stored as fat. Sometimes, the body will dip into its hepatic glycogen reserve overnight. When done consistently, time-restricted eating can also help normalize blood sugar and reduce insulin resistance in people with prediabetes.

Fat loss of any kind leads to better immune function by reducing the accumulation of fatty tissue, reducing chronic low-grade inflammation, and disrupting inflammatory signaling cascades. Reducing body fat — particularly visceral fat — may improve T cell receptor signaling for antigen presentation. Weight loss also helps restore T-cell sensitivity to antigens.

Wait at least 1 hour after waking for your first meal of the day to get the maximum benefit from time-restricted eating. Have the last meal of the day at least 2 to 3 hours before bedtime. Aim for 30 grams of protein during the eating window, preferably spread between breakfast and lunch, to help prevent late-afternoon sugar cravings.

Critical Nutrients for Immunity

A well-balanced diet emphasizing plants, high-quality protein, and good fats, will lay the macronutrient foundation for strong immunity. But even with a good basic diet, many people run low on some essential minerals, particularly if they’re battling a chronic illness or long-term inflammation.

High levels of critical nutrients are essential for maintaining a healthy immune system and rejuvenating it through fasting. Good nutrition is also essential for efficiently producing ATP within the mitochondria. B vitamins, vitamin K, iron, magnesium, selenium, and zinc are all crucial for peak immunity.

The B vitamins thiamine, riboflavin, and niacin are essential, as is the closely related alpha-lipoic acid, along with amino acids such as carnitine, cysteine, and coenzyme Q10 (ubiquinone or CoQ10).

Iron is crucial for an effective immune system. Low serum iron is a common response to infection. It’s the body’s way of slowing the progress of the infection by keeping microbes from accessing the iron they need to reproduce and spread. At the same time, immune system cells need iron to support their metabolism. When iron is scarce, the mitochondria in immune cells can’t generate enough energy. They become less effective at fighting infection and generating immune memory to fight future infections.

Iron deficiency is one of the most common micronutrient deficiencies worldwide, particularly among pregnant women, the elderly, and hospitalized patients. Iron supplements can raise low serum iron levels and help maintain a healthy balance between enough iron to support immune system cells while also limiting the iron supply to pathogens.

Magnesium is essential for hundreds of enzymatic processes in the body. The immune system is vital for forming many coenzymes and cofactors needed for the complex signaling within and among white blood cells and for developing antibodies.

Most Americans are magnesium deficient. Low magnesium can contribute to developing a cytokine storm, a severe immune reaction to an infection in which the body releases too many cytokines into the blood too quickly, and may also contribute to autoimmunity. 

Magnesium is also needed to produce the enzymes that metabolize vitamin D. Consequently, magnesium deficiency will reduce the effectiveness of vitamin D supplements.

Selenium is an essential micronutrient that has a crucial role in optimal immune responsiveness. It is a potent antioxidant that helps lower oxidative stress and reduce inflammation, ultimately enhancing immunity. Selenium deficiency leads to less robust immune responses to viruses and bacteria.

Zinc is a trace mineral for dietary purposes, but large quantities are essential for the immune system. Some researchers even call it the gatekeeper of immune function, given its importance in cytokine signaling and for mobilizing the cells of the adaptive immune system. Low zinc levels are known to increase susceptibility to viral infection.

Zinc is necessary for maintaining the integrity of the pulmonary and intestinal mucosal barriers. It’s also essential for the proper function of the pathways that trigger T cell and B cell proliferation in response to infection.

As a co-factor for many enzymes involved in immune cell function, zinc also balances pro- and anti-inflammatory immune processes.

Curcumin. In addition to vitamin and mineral supplements to support immunity, some botanical supplements can be beneficial. Curcumin, the active ingredient in the traditional turmeric spice, can potently modulate both innate and adaptive immune cells. Turmeric comes from Curcuma longa, a root used in traditional Ayurvedic medicine for thousands of years to modulate inflammation and immunity. Curcumin at low levels has been shown to enhance the production of antibodies. It has also been shown to reduce the production of pro-inflammatory cytokines, which may help prevent or attenuate damaging cytokine storms in response to infection.

Curcumin can also enhance antibody responses, which may modulate the activation of T cells, B cells, macrophages, neutrophils, natural killer cells, and dendritic cells. Curcumin can also down-regulate the expression of various proinflammatory cytokines, including TNF-alpha, IL-1, IL-2, IL-6, IL-8, IL-12, and chemokines, by inhibiting the transcription factor NF-kappaB. Curcumin can affect the expression of enzymes that are hallmarks of inflammation in autoimmune diseases, including lipooxygenase and cyclooxygenase (COX). This often makes curcumin beneficial in reducing pain and other symptoms of osteoarthritis, allergy, and asthma.

Intermittent fasting is a virtuoso of sorts since it provides a myriad of health-promoting functions that support immune rejuvenation. Adhering to intermittent fasting, you can have an immune system that functions optimally resulting in immune resilience.

Robert G. Silverman

Dr. Robert Silverman is a chiropractic doctor, clinical nutritionist, national/international speaker, author of Amazon’s #1 bestseller Inside-Out Health, founder and CEO of Westchester Integrative Health Center. He graduated magna cum laude from the University of Bridgeport College of Chiropractic and has a Master of Science in human nutrition. The ACA Sports Council named Dr. Silverman “Sports Chiropractor of the Year” in 2015. Dr. Silverman is on the advisory board for the Functional Medicine University and is a seasoned health and wellness expert on both the speaking circuits and the media. Dr. Silverman is a thought leader in his field and practice, a frequently published author in peer-reviewed journals and other mainstream publications.

Dr. Silverman was the principal investigator on two Level 1 laser FDA studies.

His new book, the Amazon bestseller Immune Reboot, was released in December 2022.

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