Introduction

 

Food, nutrition and health are highly interrelated and consumption of specific nutrients have a profound impact on human health. The amount and type of nutrients consumed are tightly linked to the metabolic system and the immune health and thus, inappropriate nutrient consumption is associated with development of major human diseases due to an immune system not properly functioning (1).Nutrition plays an essential role in the regulation of optimal immunological response, by providing adequate nutrients in sufficient concentrations to immune cells. There is a large number of micronutrients, such as minerals, and vitamins, as well as some macronutrients such as some amino acids, cholesterol and fatty acids demonstrated to exert a very important and specific impact on appropriate immune activity.

 

But what is the immune system? The immune system serves as the body’s defense mechanism, protecting against pathogens like bacteria, viruses, and harmful substances. It is a network of intricate systems and pathways in the body, that protects us against these harmful microbes as well as certain diseases. It recognizes foreign invaders like bacteria, viruses, and parasites and takes immediate action. Humans possess two types of immunity: innate and adaptive. Innate immunity is a first-line defense from pathogens that try to enter our bodies, achieved through protective barriers. These barriers include:

-Skin that keeps out the majority of pathogens

-Mucus that traps pathogens

-Stomach acid that destroys pathogens

-Enzymes in our sweat and tears that help create anti-bacterial compounds Immune system cells that attack all foreign cells entering the body (2).

 

Adaptive or acquired immunity is a system that learns to recognize a pathogen. It is regulated by cells and organs in our body like the spleen, thymus, bone marrow, and lymph nodes. When a foreign substance enters the body, these cells and organs create antibodies and lead to multiplication of immune cells (including different types of white blood cells) that are specific to that harmful substance and attack and destroy it. Our immune system then adapts by remembering the foreign substance so that if it enters again, these antibodies and cells are even more efficient and quick to destroy it.

Inflammation is an important, normal first step in the body’s innate immune response. When pathogens attack healthy cells and tissue, a type of immune cell called “mast cells” counterattack and release proteins called histamines, which cause inflammation. Inflammation may generate pain, swelling, and a release of fluids to help flush out the pathogens. The histamines also send signals to discharge even more white blood cells to fight pathogens. However, prolonged inflammation can lead to tissue damage and may overwhelm the immune system. The inflammatory mechanisms that compose the innate immunity are strongly influenced by nutrition, and this interaction, when perturbed, can profoundly affect disease development. The immune system is able to destroy antigens through both innate and adaptive immune cells and finally through antibodies that are specific for each pathogen (3).

 

What factors can depress our immune system?

 

• Older age: As we age, our internal organs may become less efficient; immune-related organs like the thymus or bone marrow produce fewer immune cells needed to fight off infections. Aging is sometimes associated with micronutrient deficiencies, which may worsen a declining immune function.

 

• Environmental toxins (smoke and other particles contributing to air pollution, excessive alcohol): These substances can impair or suppress the normal activity of immune cells.

 

• Excess weight: Obesity is associated with low-grade chronic inflammation. Fat tissue produces adipocytokines that can promote inflammatory processes . Research is early, but obesity has also been identified as an independent risk factor for the influenza virus, possibly due to the impaired function of T-cells, a type of white blood cell  .

 

• Poor diet: Malnutrition or a diet lacking in one or more nutrients can impair the production and activity of immune cells and antibodies.

 

• Chronic diseases: Autoimmune and immunodeficiency disorders attack and potentially disable immune cells.

 

• Chronic mental stress: Stress releases hormones like cortisol that suppresses inflammation (inflammation is initially needed to activate immune cells) and the action of white blood cells.

 

• Lack of sleep and rest: Sleep is a time of restoration for the body, during which a type of cytokine is released that fights infection; too little sleep lowers the amount of these cytokines and other immune cells.

 

As we can see from the previous list, a well-functioning immune system depends on various factors, but one of the most crucial is our nutrition. The food we eat affects our weight, body composition and availability of the essential nutrients and bioactive compounds that directly influence the immune system’s development, maintenance, and activity (4) .

 

But let’s dive more into this.

 

The cells in our body require energy from food, and immune cells are no exception. One of the best ways to support your immune system is to eat enough. In order to make and support immune cells, your body needs energy, which comes from the food and drinks you put in your body. In addition to fueling immune cells, the different macronutrients and micronutrients offer support on many other levels:

• Work as antioxidants 

• Produce antibodies

• Provide structure for immune cells

• Promote growth and activity of immune cells

• Produce white blood cells

• Regulate immune cells responses

• Lower oxidative stress and reduce inflammation

• Synthesis of immune cell DNA and protein

• Repair damaged cells and tissue

 

The number of studies related to the impact of nutrition on immune system is continuously increasing. The initial studies published were related to nutritional-modulation of the immune function andwere mostly based on the effects of micro and macronutrients . Lately, a wide variety of phytochemicals and other chemical biocomponents found in nutrients has been added to the list of nutritional-immuno-modulators. These biocomponents affect the immune function but are not crucial for maintaining normal cell metabolism and function . Cases in point are several phytochemicals demonstrated to exert impressive positive immune effects (3) .

In light of the strong effects that nutrients have on the immune system, and we will list in the following paragraphs, it can be concluded that a rich-nutrient diet is rigorously required in order to maintain an adequate health status. This is in addition to the fact that nutrients are the main factors for survival, including cell proliferation, specialization, development of tissue and organs growth, energy supply, and the immune defense function (4) .

Moreover, nutritional deficiencies are closely associated with impaired immune response and loss of the host resistance to infection . On the one hand, in less developed regions, malnutrition continues to be a major health problem since it is associated with a higher incidence of morbidity and mortality usually linked with the higher prevalence of bacterial and parasitic infection diseases in these regions . In contrast, developed countries present an inadequate diet consumption, with no real nutritional value, accompanied by excess calories (5) . Therefore, malnutrition due to undernutrition or to consumption of poor diets, deficient in macro- and micronutrients, reduce the effectiveness of the immune system, not only by causing a deterioration of the immune protection but also reducing its efficacy in appropriate elimination of the pathogens, thus making people unprotected to a vast variety of diseases.

To clarify all these aspects, it is essential to understand the meaning of an adequate diet and to recognize the harmful effect of processed foods that impact the immune system. As alluded to earlier, nutrition plays an essential role in the regulation of optimal immunological response, by providing adequate nutrients in sufficient concentrations to the immune cells. In such a manner, the immune system can initiate effective responses against pathogens. In order to avoid chronic inflammation, nutrients stemmed from the diet exert significant effects in initiating this quick response (6) . When the dietary nutrients are insufficient or inefficient, the supply of these elements to the immune system cells is significantly spared and immunity is compromised.

 

Does an Immune-Boosting Diet Exist?

Different nutrients play different roles in supporting immune health, so there are no “super foods” that can do it all. Therefore, eating enough nutrients as part of a varied diet is required for the health and function of all cells, including immune cells. Diets that are limited in variety and lower in nutrients, such as consisting primarily of ultra-processed foods and lacking in whole organic foods, can negatively affect a healthy immune system . Certain dietary patterns may better prepare the body for microbial attacks and excess inflammation, but it is unlikely that individual foods offer special protection. Each stage of the body’s immune response relies on the presence of many micronutrients. However, there are certain micronutrients such as vitamins and minerals as well as some macronutrients such as specific amino and fatty acids demonstrated to exert a very important and particular impact on immune modulation.

Vitamin C works as an antioxidant but  is also involved in the modulation of a wide variety of immune functions by boosting the production and function of white blood cells. Vitamin C is also involved in gene transcription as well as in hydroxylation reactions (7) . Through its main function as an antioxidant, it is capable to defend the body against reactive oxygen species that are the result of the activity of toxins and pollution. It can be found in foods such as :

• Orange, grapefruit,guava, black currant, lemon, lychee 

• Broccoli, spinach, tomato, artichoke

• Strawberry, mango, papaya, kiwi.

• Kale, bell pepper, Brussels sprouts, snow peas, green chili, kohlrabi, parsley

 

 

 

Vitamin D is both a nutrient we eat and a hormone our bodies make. It has long been known to help the body absorb and retain calcium and phosphorus and is critical for building bone. Additionally, recent studies show that vitamin D can modulate the immune response in our body, reduces cancer cell growth, help control infections and reduce inflammation. Deficiency has been linked to increased susceptibility to respiratory infections and osteomalacia/osteoporosis. Our body can synthesize vitamin D when our skin is exposed to the sun, which is the primary natural source of vitamin D, but many people have insufficient levels because they live in places where sunlight is limited in winter, or because they have limited sun exposure due to being inside much of the time. Foods that contain significant quantities are:

• Salmon, tuna

• Mushroms

• Beef liver

 

 

 

Vitamin A works as an antioxidant and additionally helps in the production of white blood cells while regulating the immune cell responses. Deficiency of this vitamin affects processes related to appropriate cytokines release and antibody production. Additionally, vitamin A deficiency is associated with a reduced production of natural killer cells, monocytes or macrophages, and impaired maturation and proliferation of T- and β-lymphocytes and supports the integrity of skin and mucosal barriers, the first line of defense against pathogens. Vitamin A supplementation cuts down morbidity and mortality in various infectious diseases. Found in foods like:

• Carrot, bell pepper, artichoke

• Sweet potato, pumpkin, squash, russet potato

• Spinach, kale, cooked collards, cooked turnip green, chard, lettuce

• Mango, papaya, apricot, cantaloupe, red grapes, watermelon, tangerine, nectarine, guava, passion fruit

• Beef, lamb, goose liver

• Bluefin tuna, trout

• Goat, limburger, cheddar, blue, and feta cheeses

 

 

Vitamins B1, B2, B3, B6 and B12 are water soluble vitamins in charge to carry out essential, inter-related roles for appropriate cellular functioning and additionally help the body make healthy red blood cells and aid in maintaining the lymphatic system. These vitamins act as efficient co-enzymes in a vast array of catabolic and anabolic enzymatic reactions and they are essential cofactors for many important cellular metabolic pathways that assist our immune response. They can be found in foods as:

• Legumes, beans

• Spinach, kale, arugula, asparagus, turnip greens, romaine lettuce, Brussels sprouts, broccoli, beets

• Orange, grapefruit, lemon, lime, papaya, banana, avocado

• Peanuts, sunflower seeds

• Wheat germ

• Poultry and meat products.

 

 

 

Selenium is involved in the functioning of the thyroid metabolism and the cardiovascular system as well as in ensuring a functional immune system and preventing cancer. It promotes the growth and activity of immune cells while lowers oxidative stress and inflammation. Found in:

• Seafood, poultry

• Cottage cheese

• Whole grains, including whole grain breads and pasta, brown rice, barely, quinoa, rye, millet

 

 

 

Zinc is responsible for the inflammatory cytokines number reduction and promotes growth and activity of immune cells. Zinc deficiency is associated with impaired immune function and slower wound healing.

• Nuts, cashews

• Oysters and shellfish

• Chickpeas

 

 

Iron supports the proliferation of immune cells and the production of enzymes that fight infections and carries oxygen to immune cells. Found in :

• Red meat, chicken, turkey

• Canned light tuna, sardines

• Clams, oysters

• Beans

 

 

Macronutrients:

 

 Amino Acids: Besides micronutrients, macronutrients, such as proteins and amino acids, also play an important role in the activity of the immune system. Proteins are formed from amino acids that are essential in the construction of other proteins among which antibodies and cytokines that are typical proteins belonging to the immune system . Essential amino acids from protein-rich foods like poultry, fish, and tofu are critical for building immune cells and antibodies (7) . Amino acids such as L-arginine and L-tryptophan are responsible and critical for macrophages’ appropriate immune activity. The decline of protein metabolism that is related to the diminishing concentration of certain amino acids, leads to the endoplasmic reticulum (ER) stress. As a result, the T cells which produce pro-inflammatory cytokines are activated  . For example, the deficiency of Arginine is correlated with reduced T cell ability to trigger tumor immunity (14) .

 

Healthy Fats: Polyunsaturated fatty acids (PUFAs) are essential fatty acids that contain more than one double bond in their backbone. PUFAs are divided into two main groups: Omega-3s and omega-6s. Together with cholesterol, PUFAs are essential for cell membrane integrity, development and maintenance in the homeostasis of cell function. Omega-3 fatty acids, found in fatty fish, walnuts, and flaxseeds, reduce inflammation and promote a balanced immune response. Omega-3s from the PUFAs group are involved in anti-inflammatory reactions through the inhibition of ARA from the membrane, which is the main precursor for pro-inflammatory eicosanoids (9) . They are capable to modulate immune and inflammatory responses through intensity and duration. On the one hand, pro-inflammatory effects are linked to fever, vasodilatation and intensification of pain. On the other hand, they could have anti-inflammatory effects by blocking natural killer activity and lymphocyte proliferation. However, most importantly is the ratio between the 2 groups of PUFAs. Simopoulos, tried to shade light in this regards and proposed that a low omega-6/omega-3 ratio in women is responsible for the decrease in breast cancer risk. She additionally concluded that a lower ratio is associated with a general decrease in very common chronic diseases in the Western society (10) .

 

Cholesterol in food is often misunderstood. In reality cholesterol is needed for all cellular membranes, making its biosynthesis and regulatory pathways ubiquitous across cell types, including immune cells. Recent studies have underlined an emerging role for cholesterol as an important modulator of innate and adaptive immunity activity. There are mainly two types of cholesterol the high-density lipoprotein (HDL) or “good” cholesterol, and low-density lipoprotein (LDL) or “bad” cholesterol. If there is too much LDL cholesterol in the blood, it builds up in the walls of the blood vessels, causing them to narrow and stiffen. A buildup of LDL cholesterol reduces blood flow and can increase the risk of heart attack or stroke. HDL cholesterol can move LDL cholesterol from the blood to the liver, which breaks it down for disposal as waste. HDL cholesterol is referred to as good cholesterol because it reduces the level of cholesterol in the blood. Higher HDL levels are linked to a reduced risk of heart attack and heart disease. Foods that can raise HDL cholesterol are :

• Olive Oil

• Nuts

• Fatty Fish

• Seeds

• Cocoa and Dark Chocolate

• Avocado

• Legumes and Beans

• Fruits and Vegetables

• Whole Grains

 

 

 Gut Health and Immunity

 

It would be a big mistake to analyse the relation between the food we eat and our immune system , without mentioning the gut. The gut plays a pivotal role in immunity, as approximately 70% of the immune system resides in the gastrointestinal tract. The human gut is home to trillions of microorganisms, collectively known as the gut microbiome. These microorganisms—bacteria, fungi, viruses, and other microbes—play an integral role in maintaining health by interacting closely with immune cells to regulate their activity.

The diet plays a large role in determining what kinds of microbes live in our intestines. A typical Western diet high in refined sugar and processed foods can promote disturbances in healthy intestinal microorganisms, resulting in chronic inflammation of the gut, which is associated with suppressed immunity (12) . A high-fiber plant-rich diet with plenty of fruits, vegetables, whole grains, and legumes appear to support the growth and maintenance of beneficial microbes (13) . Certain helpful microbes break down fibers into short chain fatty acids, which have been shown to stimulate immune cell activity. Probiotic foods contain live helpful bacteria, and prebiotic foods contain fiber and oligosaccharides that feed and maintain healthy colonies of those bacteria. Therefore, a diet containing probiotic and prebiotic foods may be beneficial.

 

Probiotic foods include kefir, yogurt with live active cultures, fermented vegetables sauerkraut, tempeh kombucha tea, kimchi and miso.

 

Prebiotic foods include garlic, onions, leeks, asparagus, Jerusalem artichokes, dandelion greens, bananas, and seaweed. However, a more general rule is to eat a variety of fruits, vegetables, beans, and whole grains for dietary prebiotics.

 

Conclusion

The relationship between food and the immune system is profound and multifaceted. A balanced diet rich in vitamins, minerals, and other bioactive compounds provides the foundation for a robust immune system, while poor dietary choices can weaken it and increase vulnerability to diseases. Recognizing the pivotal role of nutrition in immune health empowers individuals to make informed food choices, fostering not only immunity but also overall well-being. As science continues to uncover the intricate connections between diet and immunity, one thing remains clear: Hippocrates, the “father of medicine” knew it al along when thousands of years ago suggested : “Let food be thy medicine and medicine be thy food“.

 

 

 

References

 

1. Gombart A, Pierre A, Maggini S. A review of micronutrients and the immune system–working in harmony to reduce the risk of infection. Nutrients. (2020) 12:236. 10.3390/nu12010236 .
2. https://nutritionsource.hsph.harvard.edu/nutrition-and-immunity/
3. Childs CE, Calder PC, Miles EA. Diet and Immune Function. Nutrients. 2019 Aug 16;11(8).
4. Wu D, Lewis E, Pae M, Meydani S. Nutritional modulation of immune function: analysis of evidence, mechanisms, and clinical relevance. Front Immunol. (2019) 9:3160. 10.3389/fimmu.2018.03160.
5. Koithan M, Devika J. New approaches to nutritional therapy. J Nurse Practit. (2010) 6:805–6. 10.1016/j.nurpra.2010.07.001.
6. Mullero K. Malnutrition and health in developing countries. Can Med Assoc J. (2005) 173:279–86. 10.1503/cmaj.050342.
7. Chandra RK. Nutrition and the immune system: an introduction. The American journal of clinical nutrition. 1997 Aug 1;66(2):460S-3S.
8. Simopoulos A. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother. (2002) 56:365–79. 10.1016/s0753-3322(02)00253-6.
9. Molendijk I, van der Marel S, Maljaars PW. Towards a Food Pharmacy: Immunologic Modulation through Diet. Nutrients. 2019 Jun;11(6):1239.
10. Caballero S, Pamer EG. Microbiota-mediated inflammation and antimicrobial defense in the intestine. Annual review of immunology. 2015 Mar 21;33:227-56.
11. Li P, Yin Y, Li D, Kim S, Wu G. Amino acids and immune function. Br J Nutr. (2007) 98:237–52. 10.1017/S000711450769936X.
12. Szefel J, Danielak A, Kruszewski W. Metabolic pathways of L-arginine and therapeutic consequences in tumors. Adv Med Sci. (2019) 64:104–10. 10.1016/j.advms.2018.08.018.
13. Rubio-Patiño C, Bossowski J, De Donatis G, Mondragón L, Villa E, Aira L, et al. Low-protein diet induces IRE1α-dependent anticancer immunosurveillance. Cell Metab. (2018) 27:828.e–42.e. 10.1016/j.cmet.2018.02.009.
14. Szefel J, Danielak A, Kruszewski W. Metabolic pathways of L-arginine and therapeutic consequences in tumors. Adv Med Sci. (2019) 64:104–10. 10.1016/j.advms.

 

Part 1 . History and use of sugar

     Imagine a chemical substance that can intoxicate us, can infuse us with energy, and can do so when taken by mouth. It doesn’t have to be injected, smoked, or snorted for us to experience its sublime and soothing effects. Imagine that it mixes well with virtually every food and particularly liquids, and that when given to infants it provokes a feeling of pleasure so profound and intense that its pursuit becomes a driving force throughout their lives. Overconsumption of this substance may have long-term side effects, but there are none in the short term—no staggering or dizziness, no slurring of speech, no passing out or drifting away, no heart palpitations or respiratory distress. When it is given to children, its effects may be only more extreme variations of the apparently natural emotional roller coaster of childhood, from the initial intoxication to the tantrums and whining of what may or may not be withdrawal a few hours later. More than anything, our imaginary substance makes children happy, at least for the period during which they’re consuming it. It calms their distress, eases their pain, focuses their attention, and then leaves them excited and full of joy until the dose wears off. The only downside is that children will come to expect another dose, perhaps to demand it, on a regular basis, so more or less works like a drug. Well, this substance exists and is called sugar!
    Biochemically, the term “sugar” refers to a group of carbohydrate molecules consisting, as the word “carbohydrate” implies, of atoms of carbon and hydrogen. The names of these carbohydrates all end in “-ose”—glucose, galactose, dextrose, fructose, lactose, sucrose, etc. and all of them will dissolve in water and they all taste sweet to us to a greater or lesser extent. When physicians or researchers refer to “blood sugar,” they’re talking about glucose, because it constitutes virtually all of the sugar circulating in our blood.    However, the more common usage of “sugar” refers to sucrose, the white crystalline variety that we put in our coffee or tea or sprinkle on our morning cereal. Sucrose in turn is composed of equal parts glucose and fructose, the two smaller sugars (monosaccharides, in the chemical lingo) bonded together to make the larger one (a disaccharide). Fructose, found naturally in fruits and honey, is the sweetest of all these sugars, and it’s the fructose that makes sucrose particularly sweet. Although sugars like fructose, glucose, and sucrose are found naturally in foods that humans have always eaten, modern foods often contain refined, processed sugars that are anything but natural.
    Without refining, the juice of sugarcane is for local consumption only. Within a day of cutting, the sugarcane stalks will begin to ferment and then rot. But the juice can be squeezed or crushed or pounded out of the cane, and that, in turn, as farmers in northern India discovered by around 500 B.C., can be transformed into a raw sugar by cycles of heating and cooling—a “series of liquid-solid operations.” The sugar crystallizes as the liquid evaporates. One end product is molasses, a thick brown viscous liquid; another, requiring greater expenditures of time and effort, is dry crystalline sugar of colors ranging from brown to white. The greater the refining effort, the whiter and more pure is the end product. When cultivated with the instruments of modern technology, sugarcane can produce (as the sugar industry and nutritionists would state in its defence repeatedly in the twentieth century) more calories per acre to feed a population than any other animal or plant. It can survive years of storage; it travels well; it can be consumed on arrival unheated and uncooked. And, unlike honey or maple syrup, it has no distinctive taste or aftertaste. Refined sugar is colourless and odourless. It is nothing more than the crystallised essence of sweet. Other than salt, it is the only pure chemical substance that humans consume. And it provides four calories of energy per gram.
    

    Anthropologists believe that sugarcane itself was first domesticated in New Guinea about ten thousand years ago. As evidence that it was revered even then, creation myths in New Guinea have the human race emerging from the sexual congress of the first man and a stalk of sugarcane. The plant is technically a grass, growing to heights of twelve to fifteen feet, with juicy stalks that can be six inches around. In tropical soils, sugarcane will grow from cuttings of the stem, and will ripen or mature in a year to a year and a half. The juice or sap from the cane, at least the modern variety, is mostly water and as much as 17% sugar. This makes the cane, sweet to chew but not intensely so. Anthropologists assume that early farmers domesticated the cane for the sweetness to be derived from chewing the stalks and the energy it provided. Well before the art of refining came along, sugarcane domestication had already spread to India, China, the Philippines, and Indonesia.
    It’s a safe bet that humans have tried to extract sugar, at one time or another, from pretty much every substance or plant that was noticeably sweet and held the promise of offering its sugar up in quantity. Honey was consumed throughout Europe and Asia before sugar displaced it, and when European colonists arrived in the New World and found no honey, they introduced honeybees, which Native Americans took to calling the “English Man’s Fly.” Native Americans were using maple syrup as a sweetener before the Europeans arrived, and they introduced the colonists to the taste. (Thomas Jefferson was a proponent of maple syrup because it rendered slave labor unnecessary. The sugar maple, he wrote, “yields a sugar equal to the best from the cane, yields it in great quantity, with no other labor than what the women and girls can bestow….What a blessing.”) But neither maple syrup nor honey can be used to sweeten cold beverages, and neither mixes well with coffee. Neither could be produced in the quantities necessary to compete with sugar. We still consume them, but in limited quantities and for limited uses.
    Crusaders brought sugar home with them to Europe after their campaigns in the Holy Land, where they encountered caravans carrying "sweet salt”. Early in the 12th century, Venice acquired some villages near Tyre and set up estates to produce sugar for export to Europe, where it supplemented honey as the only other available sweetener. Crusade chronicler William of Tyre, writing in the late 12th century, described sugar as "a most precious product, very necessary for the use and health of mankind". The first record of sugar in English is in the late 13th century.  Known worldwide by the end of the medieval period, sugar was very expensive and was considered a "fine spice", but from about the year 1500, technological improvements and New World sources began turning it into a much cheaper bulk commodity.    
    Contemporaries often compared the worth of sugar with valuable commodities including musk, pearls, and spices. Sugar prices declined slowly as its production became multi-sourced throughout the European colonies in the Americas. Once an indulgence only of the rich, the consumption of sugar also became increasingly common among the poor as well. Sugar production increased in the mainland North American colonies, in Cuba, and in Brazil. The labour force at first included European indentured servants and local Native American enslaved people. However, European diseases such as smallpox and African ones such as malaria and yellow fever soon reduced the numbers of local Native Americans. Europeans were also very susceptible to malaria and yellow fever, and the supply of indentured servants was limited. African slaves became the dominant source of plantation workers, because they were more resistant to malaria and yellow fever, and because the supply of enslaved people was abundant on the African coast. In the process of whitening sugar, the charred bones of dead enslaved people were commonly substituted for the traditionally used animal bones. During the 18th century, sugar became enormously popular. Great Britain, for example, consumed five times as much sugar in 1770 as in 1710. By 1750, sugar surpassed grain as "the most valuable commodity in European trade — it made up a fifth of all European imports and in the last decades of the century four-fifths of the sugar came from the British and French colonies in the West Indies. From the 1740s until the 1820s, sugar was Britain's most valuable import.

    Sugar was “an ideal substance,” says Sidney Mintz in his book “Sweetness and Power: The Place of Sugar in Modern History”.  “It served to make a busy life seem less so; in the pause that refreshes, it eased, or seemed to ease the changes back and forth from work to rest; it provided swifter sensations of fullness or satisfaction than complex carbohydrates did; it combined easily with many other foods, in some of which it was also used (tea and biscuit, coffee and bun, chocolate and jam-smeared bread). No wonder the rich and powerful liked it so much, and no wonder the poor learned to love it.” Unlike alcohol, which was the only commonly available psychoactive substance in the Old World until sugar, nicotine, and caffeine arrived on the scene, the latter three had at least some stimulating properties, and so offered a very different experience, one that was more conducive to the labor of everyday life. These were the “eighteenth-century equivalent of uppers,” writes the Scottish historian Niall Ferguson. “Taken together, the new drugs gave English society an almighty hit; the Empire, it might be said, was built on a huge sugar, caffeine and nicotine rush—a rush nearly everyone could experience.”
    Sugar is extraordinarily useful in food preparation, even when sweetness is not necessarily the desired result, and this is one reason why sugar in all its various names and forms is now ubiquitous in modern processed foods. Sugar allows for the preservation of fruits and berries by inhibiting the growth of micro-organisms that would otherwise cause spoiling. As such, inexpensive sugar made possible the revolution in jams and jellies that began in the mid nineteenth century . It inhibits mold and bacteria in condensed milk and other liquids by increasing what’s called the osmotic pressure of the liquid. It reduces the harshness of the salt that’s used for curing and preserving meat (and the salt increases the sweetness of the sugar). Sugar is an ideal fuel for yeast, and thus the rising and leavening of bread. The caramelisation of sugar provides the light-brown colours in the crust of bread. Dissolve sugar in water and it adds not only sweetness but viscosity, and thus creates the body and what food scientists call the “mouth feel” of a soda or juice. As a seasoning or a spice, it enhances flavours already present in the food, decreases bitterness, and improves texture.
    Mintz has argued as well, that a primary reason that helped sugar through the centuries to escape religious-based criticisms, of the kind pronounced on tea, coffee, rum, and even chocolate, is that, whatever conspicuous behavioural changes may occur when infants consume sugar, it did not cause the kind of “flushing, staggering, dizziness, euphoria, changes in the pitch of the voice, slurring of speech, visibly intensified physical activity, or any of the other cues associated with the ingestion” of these other substances. Sugar appears to be a substance that causes pleasure with a price that is difficult to discern immediately and paid in full only years or decades later. With no visible, directly noticeable consequences, as Mintz says, questions of “long-term nutritive or medical consequences went unasked and unanswered.” Most of us today will never know if we suffer even subtle withdrawal symptoms from sugar, because we’ll never go long enough without sugar to find out.
    Mintz and other sugar historians consider the drug comparison to be so fitting in part because sugar is one of a handful of “drug foods,” to use Mintz’s term, that came out of the tropics, and on which European empires were built from the sixteenth century onward, the others being, tea, coffee, chocolate, rum, and tobacco. Its history is intimately linked to that of these other “drugs”. Rum is distilled, of course, from sugarcane, whereas tea, coffee, and chocolate were not consumed with sweeteners in their regions of origin. In the seventeenth century, however, once sugar was added as a sweetener and prices allowed it, the consumption of these substances in Europe exploded. Sugar was used to sweeten liquors and wine in Europe as early as the fourteenth century; even cannabis preparations in India and opium-based wines and syrups included sugar as a major ingredient.
    The common tendency is to think of this explosion in the use of sugar by humans,  as driven by the mere fact that sugars and sweets taste good. We can call it the “pause that refreshes” hypothesis of sugar history. The alternative way to think about this is that sugar took over our diets because the first taste, whether for an infant today or for an adult centuries ago, is literally, as Michael Pollan put it, an astonishment, a kind of intoxication; “it’s the kindling of a lifelong craving, not identical but analogous to that of other drugs of abuse”. Because it is a nutrient, and because the conspicuous results of its consumption are relatively benign compared with those of nicotine, caffeine, and alcohol—at least in the short term and in small doses—it remained, as Sidney Mintz says, nearly invulnerable to moral, ethical, or religious attacks.
    A second factor in the transformation of sugar into a dietary staple—one of life’s necessities—was technology. The industrial revolution, inaugurated by Watt’s steam engine in 1765, transformed sugar production and refining just as it did virtually every other existing industry in the nineteenth century. By the 1920s, sugar refineries were producing as much sugar in a single day—millions of pounds—as would have taken refineries in the 1820s an entire decade. With sugar becoming so cheap that everyone could afford it, the manner in which we consumed it would change as well. Not only did we add sugar to hot beverages and bake it into wheat products or spread it on top—jams and jellies were two foods that cheap, available sugar made ubiquitous, since fruit could now be preserved at the end of the growing season and provide nutrition (sweetened, of course) all year round—but the concept of a dessert course emerged for the first time in history in the mid-nineteenth century, the expectation of a serving of sweets to finish off a lunch or dinner. The industrial work break also emerged, as a new era of factory workers learned to partake of some combination of nicotine, caffeine, and sugar; cigarettes, coffee and tea, and sweetened biscuits or candy could all be purchased inexpensively.
    

      Lastly, it is worth mentioning how sugar and sweets became, after thousands years of use, a synonymous to love and affection and the language with which we communicate them—“sweets,” “sweetie,” “sweetheart,” “sweetie pie,” “honey,” “honeybun,” “sugar,” and all manner of combinations and variations. Sugar and sweets became a primary contribution to our celebrations of holidays and accomplishments, both major and minor. For some people sugar and sweets have become the tools they used to reward their children’s accomplishments, to demonstrate the love and pride in them, to motivate them, to entice them. Sweets have become the currency of childhood and parenting.
    

 

References

Taubes G. (2017); “The case against sugar” , Alfred A. Knopf, New York,.

Mintz, S. W. (1991) ; “Pleasure, Profit, and Satiation.” In Seeds of Change, ed. J. J. Viola and C. Margolis (Washington, D.C.: Smithsonian Institution).

Mintz, S. W. (1985) ; Sweetness and Power: The Place of Sugar in Modern History. New York: Penguin.

Pollan, M.  (2008);  In Defense of Food. New York: Penguin.

Pollan, M. (2002) ; “When a Crop Becomes King.” New York Times Magazine, July 19: A17.

Pollan, M. (2001) ; The Botany of Desire: A Plant’s-Eye View of the World. New York: Random House.

Ferguson, N. (2002) ; Empire: The Rise and Demise of the British World Order and the Lessons for Global Power. London: Penguin.

Twain, M. (2010);  Autobiography of Mark Twain: The Complete and Authoritative Edition. Vol. 1. Berkeley: University of California Press.

Sugar Research Foundation, Inc (SRF). (1945) ;  Some Facts About the Sugar Research Foundation, Inc., and Its Prize Award Program. Oct. Washington: Sugar Research Foundation, Inc.

Sugar Association, Inc. (SAI). (1978);  Sugar Association, Inc., winter meeting of the board of directors, Chicago, Ill., Feb. 9, 1978. Research projects report, Washington, D.C. Sugar Association, Inc., Records of the Great Western Sugar Company, Colorado Agricultural Archive, Colorado State
University.

Prinsen Geerligs, H. C. (2010);  The World’s Cane Sugar Industry, Past and Present. Cambridge, U.K.: Cambridge University Press. [Originally published in 1912.]

 

How to incorporate the practice of fasting in our everyday life

 

     As we saw in the first part , fasting is the voluntary avoidance of food for health, spiritual, or other reasons. It’s done by someone who is not underweight and has enough stored body fat to live off. When done correctly, fasting should not cause suffering, and certainly never death. Food is easily available, but you choose not to eat it. This can be for any period of time, from a few hours up to a few days or – with medical supervision – even a week or more. You may begin a fast at any time of your choosing, and you may end a fast at will too.

So, in theory,  anytime we are not eating ,we are intermittently fasting. But let’s dive into the science behind it.

    Intermittent fasting (IF) covers a broad class of dietary interventions that alternate periods of eating and extended fasting on recurring basis. IF interventions can include periodic 24-hour fasts, intermittent energy restriction (e.g., the 5:2 protocol), and time-restricted eating (TRE). Our bodies need a 24 hour continual source of energy just for the basic metabolic housekeeping – keeping the heart pumping blood, liver and kidney functions, the lungs sucking air, brain function etc. Since we do not eat food all the time, we have a system of storing food energy (in the liver and as body fat) for times where we are not eating, like when we are sleeping for example.  At moments like these , our body needs to pull some of the food energy we’ve stored away to keep our vital organs running. This is the reason we do not die in our sleep every single night.
   So, it becomes obvious that IF is not something unusual but a part of everyday, normal life. Yet somehow we have missed its power and overlooked its therapeutic potential. For example, you may be already intermittently fasting every day , between the dinner and the breakfast of the next day, a period that for most people is approximately 10 hours. Although the main benefits of IF start to appear after 12 hours of not ingesting any food, the 10 hours you stayed without feeding your self still count as IF. Just consider the term “breakfast.” It refers to the meal that breaks your fast – which is done daily in the morning. In that sense, even the English language implicitly acknowledges that fasting should be considered a part of everyday life.
    As we saw in the first part of this series,  at its very core, fasting simply allows the body to use its stored sources of energy – blood sugar and body fat. This is an entirely normal process and humans have evolved these storage forms of food energy precisely so that we can fast for hours or days without detrimental health consequences. Blood sugar and body fat is merely stored food energy ready to fuel the body when food is not available. By fasting, we are lowering blood sugar and body fat by using them precisely for the reason we store them. So, if we need to restore balance in our dietary patterns , if we need to achieve metabolic flexibility or if we need to lose weight, we may simply need to increase the amount of time spent burning food energy.

That’s intermittent fasting.

Intermittent fasting benefits

IF’s most obvious benefit is weight loss. However, there are many potential benefits beyond this, some of which have been known since ancient times.  The fasting periods were often called ‘cleanses,’ ‘detoxifications’ or ‘purifications,’ but the idea is similar – to abstain from eating food for a certain period of time. People believed that this period of abstinence from food would clear their systems of toxins and rejuvenate them. Since we talked excessively about the benefits of fasting in general in the first part of this series, in this post i will just mention the most important benefits of IF reported through scientific research :

• Weight and body fat loss - improved body composition.
• Lowered blood insulin and sugar levels
• Lowered blood insulin and glucose levels - Reversal of type 2 diabetes
• Reduced hemoglobin A1c (A1c) levels
• Improved mental clarity and concentration
• Increased energy
• Increased growth hormone, at least in the short term
• Improved blood cholesterol profile
• Increased longevity
• Activated cellular cleansing by stimulating autophagy
• Reduction of inflammation

 

How can we apply in our everyday life the practice of IF?  Here, i am presenting some of the most important protocols.

Protocols

 

    1.  Time-restricted eating (12:12 fasting, 14:10 - 16:8 fasting, 18:6 fasting, and 20:4 fasting)

    While IF, is a term used to describe a lot of different protocols, it’s most often used to describe something called Time Restricted Eating (TRE)—meaning, restricting the period of time you eat to a set number of hours each day. Time restricted eating, also called time restricted feeding (TRF) in research settings, typically consists of confining all your eating to a 12-hour, 10-hour, 8-hour, 6-hour, or 4-hour window, and fasting the remainder of the day. Lets see them analytically :

• 12-hour fasting

Many experts view a 12-hour eating/12-hour fasting window (think: eating breakfast at 8 a.m. and wrapping up dinner by 8 p.m.) as a great, safe place to start for anyone. It shouldn’t be that difficult , since one can fit the 8 hours of sleep in the 12 hour fasting window, therefore the challenge here is to remain without food for 4 more hours.  Piece of cake !

• 14:10 and 16:8 fasting

Some of the most popular versions of TRE are the 14:10 or 16:8 fasting plans, which consist of a daily 14-hour and 16-hour fast while confining your eating to an 10-hour and 8-hour window respectively. If you can't live without breakfast, slot your food earlier in the day (8 a.m. to 6 pm or 4 p.m.). If you prefer an early dinner, eat in the middle of the day (11 a.m. to 9 pm or 7 p.m.). If you're someone who regularly goes out with friends for late dinners, schedule your eating hours later in the day (1 pm to 11pm or 9 pm).

• 18:6 fasting

Also popular, but a bit more intense, is the 18:6 fasting plan, which is a daily 18-hour fast where you confined your eating to a 6-hour window. If your goal is weight loss and you’ve experienced a plateau on a 16:8 plan, this is the logical next step. While more research is needed, an 18:6 fast likely helps your body burn stored carbohydrates (glycogen) faster so you can start burning fat (in the form of ketones) for fuel, and some believe it may be enough to activate autophagy—a cellular clean-up process that’s associated with longevity.

• 20:4 fasting

The most restrictive of the popular TRE regimens is the 20:4 fast (sometimes called the “warrior diet”), which is a daily 20-hour fast where you confined your eating to a 4-hour window. This essentially breaks down to one meal a day and is not for beginners—you need to work your way up. Compared to a 16:8 or 18:6 fast, it’s speculated that you will burn more fat, lose more weight, and experience greater autophagy on a 20:4 diet, since the fasting hours last for almost all day.

 

       2.  Alternate-day fasting (36 hour fast)

      Also under the umbrella of intermittent fasting is alternate-day fasting (ADF). ADF is just how it sounds: You only eat every other day. So, practically,  you fast for 36 hours on a recurring basis. You finish dinner on day 1 at 7 pm for instance, and you would skip all meals on day 2, and not eat again until breakfast at 7 am on day 3. So that is a total of 36 hours of fasting followed by an 12-hour eating window. While some purists only consume water, herbal tea, and moderate amounts of black coffee on fasting days, others employ the 25 percent rule. In this version, you consume 25 percent of your normal caloric intake on fast days. This protocol has shown really good results for weight loss and reducing inflammation and while many clinics often recommend 36-hours fasts 2-3 times per week for reversing type 2 diabetes, alternate-day fasting is a more extreme approach to IF that may be hard to sustain over the long term. For obvious reasons, is not for beginners, and it should be reserved for specific medical cases.

 

    3.   5:2 plan

    A slightly easier variation of ADF, the 5:2 plan allows you to eat normally for five days every week while eating only 500 to 600 calories on the other two days. You can choose whichever two days of the week you prefer, as long as there is at least one non-fasting day in between them. One common way of planning the week on this protocol , is to fast on Mondays and Thursdays, with two or three small meals, then eat normally for the rest of the week. It’s important to emphasize that eating “normally” does not mean you can eat anything. If you binge on junk food, then you probably won’t lose any weight, and you may even gain weight.

 

Where to place your TRE window?

     The ideal placement of your eating and fasting window will likely depend on a number of factors—work schedule, social obligations, fitness routine, and simply what feels best for your body—but a growing body of research seems to suggest that an earlier eating window may be better. A small but rigorously controlled randomised crossover study from 2019 found that when participants ate between 8 a.m. and 2 p.m., they fared much better than when they ate the same three meals on an 2 p.m. to 8 p.m. schedule.  Moreover , they had lower blood glucose levels during the day and overnight, lower insulin levels, and an ideal cortisol pattern (with levels higher in the morning and lower at night)—all of which suggests an improvement in circadian rhythm. More surprisingly, though, was that after just four days, this earlier eating schedule increased the expression of the SIRT1 gene (associated with longevity and healthy aging) and the LC3A gene (a biomarker of autophagy).

 

 

How do you manage hunger?

   The million dollar question! “If i am hungry in only 3 hours after eating , how will i be able to fast for many more hours?” … Hunger is not so simple as your stomach being ’empty’. Hunger is, in fact, a highly susceptible state with a complex hormonal regulation at play. In essence, there are two major components to hunger: The unconditioned biological stimuli – that is, the part that will normally stimulate hunger naturally (smells, sights, and tastes of food) and the conditioned stimuli (learned – movie, lecture, morning etc). These conditioned responses can be very powerful and cause great hunger. If for example we consistently eat breakfast every single morning at 7:00am, lunch at 12:00 and dinner at 6:00pm, then the time of the day itself becomes a conditioned stimulus for eating. Even if we ate a huge meal at dinner the night before, and would not otherwise be hungry in the morning, we may become ‘hungry’ because it is 7:00am. The Conditioned Stimulus (time of 7:00) causes the Conditioned Response (hunger). How to combat this? Well, intermittent fasting offers a unique solution. By skipping meals and varying the intervals that we eat, we can break our current habit of feeding 3 times a day. We no longer have a conditioned response of hunger every 3-5 hours.
    And what about the hunger we feel by the unconditioned biological stimuli during our day? The most important thing to realise is, that this type of hunger, usually passes like a wave. It comes and it goes. That is, we may not be hungry one second, but after smelling a steak and hearing the sizzle, we may become quite ravenous. And then, we may engage in an activity and we forget after some minutes completely the steak and our hunger .  Many people worry that hunger during IF will continue to build up until it is intolerable, but this does not normally happen. Approximately 3-6 hours after we eat a meal, we start to feel hunger pangs and may become slightly cranky. But if we simply ignore it and drink a cup of tea or coffee, or we keep ourselves busy with activities , it will often pass.

 

References

Heilbronn LK, Smith SR, Martin CK, Anton SD, Ravussin E. Alternate-day fasting in nonobese subjects: effects on body weight, body composition, and energy metabolism. Am J Clin Nutr. 2005 Jan;81(1):69-73. doi: 10.1093/ajcn/81.1.69. PMID: 15640462.

Tinsley GM, La Bounty PM. Effects of intermittent fasting on body composition and clinical health markers in humans. Nutr Rev. 2015 Oct;73(10):661-74. doi: 10.1093/nutrit/nuv041. Epub 2015 Sep 15. PMID: 26374764.

Nowosad K, Sujka M. Effect of Various Types of Intermittent Fasting (IF) on Weight Loss and Improvement of Diabetic Parameters in Human. Curr Nutr Rep. 2021 Jun;10(2):146-154. doi: 10.1007/s13668-021-00353-5.

Halberg N, Henriksen M, Söderhamn N, Stallknecht B, Ploug T, Schjerling P, Dela F. Effect of intermittent fasting and refeeding on insulin action in healthy men. J Appl Physiol (1985). 2005 Dec;99(6):2128-36. doi: 10.1152/japplphysiol.00683.2005. Epub 2005 Jul 28. PMID: 16051710.

 

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. doi:10.1002/oby.22065

 

Sydney G O'Connor, Patrick Boyd, Caitlin P Bailey, Marissa M Shams-White, Tanya Agurs-Collins, Kara Hall, Jill Reedy, Edward R Sauter, Susan M Czajkowski, Perspective: Time-Restricted Eating Compared with Caloric Restriction: Potential Facilitators and Barriers of Long-Term Weight Loss Maintenance, Advances in Nutrition, Volume 12, Issue 2, March 2021, Pages 325–333

 

Bachman JL, Raynor HA. Effects of manipulating eating frequency during a behavioral weight loss intervention: a pilot randomized controlled trial. Obesity (Silver Spring). 2012 May;20(5):985-92. doi: 10.1038/oby.2011.360. Epub 2011 Dec 15. PMID: 22173575.

Munsters MJ, Saris WH. Effects of meal frequency on metabolic profiles and substrate partitioning in lean healthy males. PLoS One. 2012;7(6):e38632. doi: 10.1371/journal.pone.0038632. Epub 2012 Jun 13. PMID: 22719910; PMCID: PMC3374835.

 

Sievert K, Hussain S M, Page M J, Wang Y, Hughes H J, Malek M et al. Effect of breakfast on weight and energy intake: systematic review and meta-analysis of randomised controlled trials BMJ 2019; 364 :l42 doi:10.1136/bmj.l42

Leonie K Heilbronn, Steven R Smith, Corby K Martin, Stephen D Anton, Eric Ravussin, Alternate-day fasting in nonobese subjects: effects on body weight, body composition, and energy metabolism, The American Journal of Clinical Nutrition, Volume 81, Issue 1, January 2005, Pages 69–73.

 

Kahleova H, Belinova L, Malinska H, Oliyarnyk O, Trnovska J, Skop V, Kazdova L, Dezortova M, Hajek M, Tura A, Hill M, Pelikanova T. Eating two larger meals a day (breakfast and lunch) is more effective than six smaller meals in a reduced-energy regimen for patients with type 2 diabetes: a randomised crossover study. Diabetologia. 2014 Aug;57(8):1552-60. doi: 10.1007/s00125-014-3253-5. Epub 2014 May 18. Erratum in: Diabetologia. 2015 Jan;58(1):205.

 

Jamshed, H., Beyl, R. A., Della Manna, D. L., Yang, E. S., Ravussin, E., & Peterson, C. M. (2019). Early Time-Restricted Feeding Improves 24-Hour Glucose Levels and Affects Markers of the Circadian Clock, Aging, and Autophagy in Humans. Nutrients, 11(6), 1234. https://doi.org/10.3390/nu11061234.

 

Varady, K. A., Bhutani, S., Klempel, M. C., Kroeger, C. M., Trepanowski, J. F., Haus, J. M., Hoddy, K. K., & Calvo, Y. (2013). Alternate day fasting for weight loss in normal weight and overweight subjects: a randomized controlled trial. Nutrition journal, 12(1), 146.

Johnstone AM, Faber P, Gibney ER, Elia M, Horgan G, Golden BE, Stubbs RJ. Effect of an acute fast on energy compensation and feeding behaviour in lean men and women. Int J Obes Relat Metab Disord. 2002 Dec;26(12):1623-8.

Johnstone AM, Faber P, Gibney ER, Elia M, Horgan G, Golden BE, Stubbs RJ. Effect of an acute fast on energy compensation and feeding behaviour in lean men and women. Int J Obes Relat Metab Disord. 2002 Dec;26(12):1623-8. doi: 10.1038/sj.ijo.0802151. PMID: 12461679.

 

"Our food should be our medicine.  Our medicine should be our food.  But to eat when you are sick is to feed your sickness."
                                               - Hippocrates

    Fasting is one of the most ancient and widespread healing traditions in human history. This solution has been practiced by virtually every culture and religion on earth. Hippocrates of Cos (c460 – c370 BC) is widely considered the father of modern medicine. Among the treatments that he prescribed and championed was the practice of fasting. The ancient Greek writer and historian Plutarch (c46 AD– c120 AD) also echoed these sentiments. He famously wrote, “Instead of using medicine, better fast today”. Ancient Greek thinkers Plato and his student Aristotle were also strong supporters of fasting.
    The ancient Greeks believed that medical treatment could be observed from nature. Humans, like most animals, do not eat when they become sick. For this reason, fasting has been called the ‘physician within’. This fasting ‘instinct’ that makes dogs, cats and humans anorexic when sick. This sensation is certainly familiar to everybody. Consider the last time you were sick with the flu. Probably the last thing you wanted to do was eat. So, fasting seems to be a universal human instinct to multiple forms of illnesses. Thus fasting is ingrained into human heritage, and as old as mankind itself. The ancient Greeks also believed that fasting improves cognitive abilities. Think about the last time you ate a huge meal. Did you feel more energetic and mentally alert afterwards? Or, instead did you feel sleepy and a little dopey? More likely the latter. Blood is shunted to your digestive system to cope with the huge influx of food, leaving less blood going to the brain. Result – food coma.
    Fasting is also widely practiced for spiritual purposes and remains part of virtually every major religion in the world. In spiritual terms, it is often called cleansing or purification, but practically, it amounts to the same thing. The practice of fasting developed independently among different religions and cultures, not as something that was harmful, but something that was deeply, intrinsically beneficial to the human body and spirit.

    So fasting is truly an idea that has withstood the test of time.  But what is exactly fasting and what does science say about it?

Fasting involves controlled, voluntary abstinence from caloric intake to achieve a physical, mental, or spiritual outcome.

     Our ancestors would regularly go days or even weeks without food. As a result, humans have evolved specific adaptations to survive, and even thrive, during periods of famine. So, in reality, the body  only exists in one of two states – the fed (high insulin) state or the fasted (low insulin) state. Either we are storing food energy (increasing stores) or we are burning stored energy (decreasing stores). It is one or the other, but not both. More analytically :

Feeding – During meals, insulin levels are raised. This allows uptake of glucose into tissues such as the muscle or brain to be used directly for energy. Excess glucose is stored as glycogen in the liver.
The post-absorptive phase – 6-24 hours after last meal .   Insulin levels start to fall. Breakdown of glycogen releases glucose for energy. Glycogen stores last for roughly 24 hours.
Gluconeogenesis – 24 hours to 2 days – The liver manufactures new glucose from lactate and amino acids in a process called “gluconeogenesis”. Literally, this is translated as “making new glucose”. In non-diabetic persons, glucose levels fall but stay within the normal range.
Ketosis – 2-3 days after beginning fasting – This is when interesting things start to happen for the body. The low levels of insulin reached during fasting, stimulate lipolysis, the breakdown of fat for energy. The storage form of fat, known as triglycerides, is broken into the glycerol backbone and three fatty acid chains. Glycerol is used also for gluconeogenesis. Fatty acids may be used for directly for energy by many tissues in the body, but not the brain. Ketone bodies instead , which are produced from fatty acids during ketosis , are capable of crossing the blood-brain barrier for use by the brain. After four days of fasting, approximately 75% of the energy used by the brain is provided by ketones. The two major types of ketones produced are beta hydroxybutyrate and acetoacetate, which can increase over 70 fold during fasting.
Protein conservation phase – >5 days – High levels of growth hormone maintain muscle mass and lean tissues. The energy for maintenance of basal metabolism is almost entirely met by the use of free fatty acids and ketones. Increased norepinephrine (adrenalin) levels prevent the decrease in metabolic rate.

   We see that the human body has well developed mechanisms for dealing with periods of low food availability. In essence, what is happening while fasting is a process of switching from burning glucose to burning fat . Fat is simply the body’s stored food energy. In times of low food availability, stored food is naturally released to fill the void. So no, the body does not ‘burn muscle’ in an effort to feed itself, at least until all the fat stores are used.

 

Lets have a look on the effects of fasting on Hormonal Adaptation

 

• Insulin

 

    Insulin and insulin resistance are major drivers of obesity. Fasting on the other hand , is the most efficient and consistent strategy to decrease insulin levels. This was first noted decades ago, and widely demonstrated scientifically afterwards. It is quite simple and obvious. All foods raise insulin, so the most effective method of reducing insulin is to avoid all foods. Blood glucose levels remain normal, as the body begins to switch over to burning fat for energy. This effect can be observed in fasting periods as short as 24-36 hours. Longer duration fasts reduce insulin even more dramatically. More recently, alternate daily fasting has been studied as an acceptable technique of reducing insulin.
    Regular fasting, in addition to lowering insulin levels, has also been shown to improve insulin sensitivity significantly. Many argue that this is the missing link in the weight loss puzzle. Most diets reduce highly insulin-secreting foods, but do not address the insulin resistance issue which is crucial in diabetics.  Weight is initially lost, but insulin resistance keeps insulin levels and body weight high. Fasting is an efficient method of reducing insulin resistance.
    Lowering insulin also rids the body of excess salt and water. Insulin causes salt and water retention in the kidney. Very low-carb diets often cause diuresis, the loss of excess water, leading to the contention that much of the initial weight loss is water. While true, diuresis is beneficial in reducing bloating, and feeling ‘lighter’. Some may also note a slightly lower blood pressure. Fasting has also been noted to have an early period of rapid weight loss. For the first five days, weight loss averages 0.9 kg/ day, far exceeding the caloric restriction and likely due to a diuresis of salt and water.

 

• Growth Hormone

 

   Growth hormone is known to increase the availability and utility of fats for fuel. It also helps to preserve muscle mass and bone density. Secretion is known to be pulsatile, making accurate measurement difficult. Growth hormone secretion decreases steadily with age. One of the most potent stimuli to growth hormone secretion is fasting. Over a five-day fasting period growth hormone secretion is more than doubled. The net physiologic effect is to maintain muscle and bone tissue mass over the fasting period.

 

• Adrenalin

 

     Adrenalin levels are increased so that we have plenty of energy to go get more food. For example, 48 hours of fasting produces a 3.6% increase in metabolic rate, not the dreaded metabolic ‘shut-down’. In response to a 4 day fast, resting energy expenditure increased up to 14%.   Rather than slowing the metabolism, instead the body revives it up. Additionally, studies show that the adrenalin-induced fat-burning does not depend upon lowering blood sugar. Presumably, this is done so that we have energy to go out and find more food.

And what about vitamins ,minerals and electrolytes?

    Concerns about malnutrition during fasting are misplaced. Insufficient calories are not a major worry, if the fat stores are quite ample. The main concern is the development of micronutrient deficiency. However, if the fasting regime is accompanied by the use of a multi-vitamin and mineral supplementation that will provide the recommended daily allowance of micronutrients , there should’t be any issue.  It is worth noting, that in 1973 a therapeutic fast of 382 days that resulted in loss of 125 kilos for a patient, was maintained with only a multivitamin potion and had no harmful effect on health . Actually, this man maintained that he had felt terrific during this entire period. The only concern may be a slight elevation in uric acid that has been described in fasting and can be solved by increased water consumption.

Additionally, evidence suggests four brain health effects linked to fasting:

• Brain cell re-generation

 

• Cognitive and psychological benefits

 

• Resilience to neurological conditions

 

• Slowing the effects of aging.

 

This research on brain health is focused on the use of ketones, molecules that as we saw before, are being produced and used by the body as a source of fuel while fasting. Administration of ketones is a well established therapy since decades for intractable epilepsy and seizures. It should be considered early in the treatment of Dravet syndrome and myoclonic-astatic epilepsy (Doose syndrome). A growing body of literature suggests also that the use of ketones may be beneficial in certain neurodegenerative diseases, including Alzheimer disease, Parkinson’s disease, and amyotrophic lateral sclerosis. In these disorders, ketones appears to be neuroprotective, promoting enhanced mitochondrial function and rescuing adenosine triphosphate production. Ultimately , dietary therapy is a promising intervention for cancer, given that it may target the relative inefficiency of tumors in using ketone bodies as an alternative fuel source.

So, let’s summarise.

    Fasting, but not low calorie diets, results in numerous physiological and hormonal adaptations that all appear to be highly beneficial on many levels. The main benefits of fasting are metabolic flexibility and weight management. In essence, fasting transitions the body from burning sugar to burning fat.  Resting metabolism is NOT decreased but instead increased.  We are, effectively, feeding our bodies through our own fat.  We are ‘eating’ our own fat.  This makes total sense since fat is, in essence, stored food. Fat is food stored away for the long term, like money in the bank.  Short term food is stored as glycogen, like money in the wallet.  The problem we have, is how to access the money in the bank.  As our wallet depletes, we become nervous and go out working to fill it again.  This prevents us from getting access to our stored money in the bank. In the same manner, as our glycogen ‘wallet’ depletes, we get hungry and want to eat.  That makes us look for food, despite the fact that there is more than enough food stored as fat in the body ‘bank’’.  How do we get to that fat to burn it? Fasting provides an easy way in.

 

References

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Drenick EJ, Hunt IF, Swendseid ME. Magnesium depletion during prolonged fasting of obese males. J Clin Endocrinol Metab. 1969 Oct;29(10):1341–1348.

Jackson IM, McKiddie MT, Buchanan KD. The effect of prolonged fasting on carbohydrate metabolism: evidence for heterogeneity in obesity. J Endocrinol. 1968 Feb;40(2):259–260.

Jackson IM, McKiddie MT, Buchanan KD. Effect of fasting on glucose and insulin metabolism of obese patients. Lancet. 1969 Feb 8;1(7589):285–287.

Thomson TJ, Runcie J, Miller V. Treatment of obesity by total fasting for up to 249 days. Lancet. 1966 Nov 5;2(7471):992–996.

Stewart, W. K., & Fleming, L. W. (1973). Features of a successful therapeutic fast of 382 days' duration. Postgraduate medical journal, 49(569), 203–209. https://doi.org/10.1136/pgmj.49.569.203

de Groot, S., Pijl, H., van der Hoeven, J., & Kroep, J. R. (2019). Effects of short-term fasting on cancer treatment. Journal of experimental & clinical cancer research : CR, 38(1), 209. https://doi.org/10.1186/s13046-019-1189-9

Grajower, M. M., & Horne, B. D. (2019). Clinical Management of Intermittent Fasting in Patients with Diabetes Mellitus. Nutrients, 11(4), 873. https://doi.org/10.3390/nu11040873

Furmli, S., Elmasry, R., Ramos, M., & Fung, J. (2018). Therapeutic use of intermittent fasting for people with type 2 diabetes as an alternative to insulin. BMJ case reports, 2018, bcr2017221854. https://doi.org/10.1136/bcr-2017-221854

Wilhelmi de Toledo F, Grundler F, Bergouignan A, Drinda S, Michalsen A (2019) Safety, health improvement and well-being during a 4 to 21-day fasting period in an observational study including 1422 subjects. PLoS ONE 14(1): e0209353. https://doi.org/10.1371/journal.pone.0209353

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Part 3. How the food we eat affects our mood and mental state.

    Our full physical and mental development is dependent on the food that we eat. Without sufficient food we would not grow, our bodies would be stunted and our physical organs would be undeveloped; moreover the development of our brain would be irrevocably harmed. But we also need high quality nutrition so that the body can repair itself fast , wounds can heal properly and cells can repair themselves as necessary. What we eat affects how our immune system works, how our genes work, and how our body responds to stress. All cells and tissues on our body , enzymes, neurotransmitters , hormones etc are made from the chemical components of the foods (and drinks) that we consume. So, we are literally what we eat.

    Additionally , the food we consume affects the microbiome of our gut. There is a plethora of studies showing how a healthier microbiome is going to decrease inflammation in the body, which consequently affects mood and  cognition. But this is just the tip of the iceberg. Known as the enteric nervous system (ENS), the gut’s brain is housed under the mucosal lining and between the muscular layers of the esophagus, the stomach, and the small and large intestines. The enteric nervous system is a rich and complicated network of neurons and neurochemicals that sense and control events in the digestive tract and, remarkably, can sense and respond to events in other parts of the body, including the brain. Amazingly, when scientists finally counted the number of nerve cells in the gut-brain, they found it contained over one hundred million neurons—more than the number of nerve cells in the spinal cord. What’s fascinating to note is that researchers have observed a significantly greater flow of neural traffic from the ENS to the head-brain than from the head-brain to the ENS. In other words, rather than the head informing the digestive system what to eat and how to metabolize, the focus of command is stationed in the belly. In addition to an extensive network of neurons, the entire digestive tract is also lined with cells that produce and receive a variety of neuropeptides and neurochemicals; the same substances, in fact, that were previously thought to be found only in the brain. These include serotonin, dopamine, norepinephrine, and glutamate. Even more eye-opening is that many hormones and chemicals previously thought to exist only in the gut were later found to be active in the brain. These include insulin, cholecystokinin, vasoactive intestinal protein, motilin, gastrin, somatostatin, thyrotropin releasing hormone, neurotensin, secretin, glucagon, and bombesin. All these foundings confirm the strong connection of the gut with the brain.

    Another compelling discovery is that the entire digestive tract is lined with specialised cells that produce and receive endorphins and enkephalins, chemicals that yield an array of sensations including joy, satisfaction, and pain relief. Most of the digestive sensations we are aware of tend to be negative ones, such as digestive upset and discomfort. Yet the warm gut feelings we sometimes experience after a satisfying meal or an exciting encounter are, in part, the enteric nervous system squirting pleasure chemicals at distant and neighbouring cells. As many of us know, the gut is often a barometer of our emotional states and stresses. Those who suffer from peptic ulcer, irritable bowel syndrome, heartburn, upset stomach, and other conditions would certainly concur. Perhaps this is why the gut produces an abundance of a class of chemicals known as the benzodiazepines. These psychoactive substances are the active ingredients in the prescription drugs Valium and Xanax. That’s right, your gut naturally produces these substances, in their exact chemical form, without a prescription and at no extra cost.

    But let’s have a look on the most common issues of mood and mental disorder. Anxiety for example is strongly related to a state of disturbance in the gut bacteria. When people experience unrelenting anxiety, then this means that they may be experiencing what is described by some theorists as an anxiety disorder. This includes panic disorder, obsessive-compulsive disorder, and social phobia and generalised anxiety disorder. Dr. Perlmutter considers that anxiety disorders are caused by a combination of factors which include the condition and processing ability of the gut, and the bacteria which inhabits it. He states: “When the balance of gut bacteria isn’t right, other biological pathways – be they hormonal, immunological or neuronal, aren’t right either. And the brain’s processing centres, such as those that handle emotions, aren’t right either. He quotes two significant experiments to substantiate his argument: In a 2011 study published in the Proceedings of the National Academy of Sciences, mice fed probiotics had significantly lower levels of the stress hormone corticosterone, than mice fed plain broth. (J.A. Bravo et al., 2011). The second study he describes was conducted at Oxford University. Neurobiologists found that giving people prebiotics (which is food for the promotion of good bacteria in the gut), resulted in positive psychological effects. What was observed by the Oxford researchers was that, compared to the placebo group, the individuals who had taken the prebiotics paid more attention to positive information, and less attention to the negative information. This effect, which has been noticed with individuals on antidepressants or anti-anxiety medication, indicated that the prebiotic group experienced less anxiety when faced with the negative stimuli. Also, the researchers discovered that the people who took the prebiotics had lower levels of cortisol, when measured via their saliva samples, which were taken in the morning, when cortisol levels are at their highest. Dr Perlmutter considers that these examples are relevant to the growing evidence of research studies that show a connection between mental health and gut bacteria, in particular in relation to anxiety.

    Another important factor in the management of anxiety involves regulating our blood sugar levels. Why can it make such a difference? The reason is because the sugar that we get in our bodies from processed foods such as white bread, white rice, white pasta, chocolates and fizzy drinks (to name a few junk foods) is immediately available, and immediately affects us. The body doesn’t have to work hard to digest the food and extract the nutrients. As a result, blood sugar rises rapidly and we can feel full of energy as a consequence. But this reaction is very bad for our body, which handles this sudden influx of sugar by releasing the hormone insulin. This informs our cells to mop up excess sugar very quickly. As a result of this activity by our insulin secretions, our blood sugar then drops, but it goes too low. Because of this drop, the hormone adrenaline is released. This is to initiate the unleashing of stored glucose, and then the experience of adrenaline is felt by the body. And as Dale Pinnock eloquently states “…adrenaline is to anxiety what petrol is to a bonfire”. You will then experience a change in your breathing rate; your heartbeat gets faster and faster; and your mind starts to race. These symptoms can be very unpleasant if you are already prone to experiencing anxiety.

    Additionally,  high calorie meals rich in trans-fats appear to stimulate immune activation.  Indeed, the inflammatory effects of a diet high in calories and trans-fatty acids have been proposed as one mechanism through which the Western diet may have detrimental effects on brain health, including cognitive decline, hippocampal dysfunction, and damage to the blood-brain barrier. Since various mental health conditions, including mood disorders, have been linked to heightened inflammation, this mechanism also presents a pathway through which poor diet could increase the risk of depression. This hypothesis is supported by observational studies which have shown that people with depression score significantly higher on measures of “dietary inflammation,” characterised by a greater consumption of foods that are associated with inflammation (eg, trans fats and refined carbohydrates) and lower intakes of nutritional foods, which are thought to have anti-inflammatory properties (eg, omega-3 fats).

    Blood sugar levels and trans-fats affect also anger levels. The are many studies that demonstrate the close relation between anger levels and diet. In a research  conducted by Professor Stephen Schoenthaler in 1983  for California State University, three thousand inmates of a prison were placed on a strict diet. The diet contained a marked reduction in sugary and refined foods. The results of this dietary restriction were as follows: There was a 25% reduction in assaults at the prison, a 21% reduction in anti-social behaviour, a 75% reduction in the use of restraints and a 100% reduction in suicides! A later study affirmed the validity of the results of Schoenthaler’s research. In 1983, in a double-blind study of 1,382 detained juvenile offenders on a sugar-restricted diet, the effects of this restricted diet were as follows: the anti-social behaviour dropped by 44% with the most outstanding reductions happening to the most serious offenders (Schoenthaler 1983). There is also research which suggests a link between trans-fats (including hydrogenated oils in processed foods), on the one hand, and aggression, irritability and impatience, on the other.  And, there have been several follow-up studies which have replicated and extended Schoenthaler’s results, demonstrating a strong link between healthy diet and more pro-social behaviour, indicative of better mood management and emotional control.  Of particular note is the finding that keeping the poor quality diet of prisoners, but adding vitamin and mineral supplements, plus fish oil supplements, will normally reduce anti-social behaviour, as levels of anger decline. And in the UK, between 1995 and 1997, at Aylesbury Young Offenders Institution, a placebo-controlled, randomised trial, was conducted by Dr Bernard Gesch (2002), in which young offenders were given food supplements (including vitamins, minerals and essential fatty acids), and it was found that they committed 37% fewer violent offences, while the inmates who received the placebo showed no such reduction; thus demonstrating that improved nutrition reduces angry outbursts (which were being fuelled by vitamin and mineral and fatty acid deficiencies).

So, which foods are recommended for improved mood and healthy mental state?

Generally, eating a balance of foods, mostly plants, gives us the nutrients we need for physical and mental health. There is no superfood for mental health. Our pattern of eating is what matters the most. A balanced and varied diet of whole and unprocessed foods provides the mix of nutrients we need to be at our best. All nutrients are important for physical and mental health. Here’s how foods from the five core food groups support our mental wellbeing:

• Fruit and vegetables provide us with fibre that feeds our good gut bacteria. Fruit and vegetables are important sources of the vitamins, minerals, and antioxidants that underpin our body’s core functions. Fermented foods, such as Kimchi , Kefir,  Kombucha or Sauerkraut, are also beneficial for our mental health, as they provide us with living good bacteria (also known as probiotics).

 

• Whole grains, cereals and legumes  are excellent sources of minerals, healthy fats, protein and fibre. They give us B vitamins, folate, and other vitamins which support brain health and functioning.

 

• Lean meats, including fish, and eggs are the best dietary sources of protein. Our body turns protein into many products, including brain chemicals that shape our mood. Moderation is key though – too much meat, particularly processed and fatty meats, can negatively affect our physical and mental health.

 

• Dairy foods like yoghurt provide us with living probiotics, which boost our gut health and in turn supports mental health.

 

• Healthy fats, especially omega-3, are essential for keeping our brain and nerves in tip-top shape. Great sources include olive oil, nuts, seeds, and oily fish like sardines, salmon, and mackerel.

 

• Water is vital for mental health. Our bodies are 65% water, and our organs (including our brain!) need water to function well. Drinking adequate water keeps our brains more alert. For most adults this is around 2 litres, or 8 cups, of water each day.

 

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