In this article:
- Apple: A Life-Extending Super-Fruit
- Apples and Increased Longevity
- Apples and Cancer-Prevention
- Quercitin in Apples and Protection Against Cancer, COVID and Alzheimer’s Disease
Apple: A Life-Extending Super-Fruit
Remember the old adage, “An apple a day keeps the doctor away.”? Clearly, many positive lifestyle and health-creating factors are required to maintain a state of true wellness; however, apples can certainly play a leading role. In recent years, exotic fruits such as acai berries, goji berries, and pomegranates have been heavily promoted commercially as being “super fruits.” However, extensive research has shown that the humble apple, readily available to nearly every shopper and modestly priced, is far more important and more deserving of recognition as a crucial health-building, life-extending food.
Much of the super fruit status of the apple is due to its being a rich source of antioxidants. Antioxidants are molecules that combat free radical activity in the body. Free radicals (harmful compounds if they supersede certain levels within the body), have been linked as contributing factors to many diseases, including Alzheimer’s disease, cancer, heart disease, and diabetes. Importantly, it’s not just a matter of ingesting antioxidant-rich foods, but also of the bioavailability (the proportion of a substance absorbed into the blood circulation, and thus, able to exert an active effect) of those antioxidants
A study performed at Cornell University that measured the bioavailability of antioxidants in 11 types of the most commonly eaten fruit, found apples have the second highest levels of bioavailability (cranberries had the highest level).1
The Roman physician Pliny described a mythical race of small people in India who “eat naught and live by the smell of apples.” Centuries ago, the English physician Dr. John Caius advised his patients to “smell a ripe sweet apple” in order to recover their strength.
Apples (a remedy for both constipation and diarrhea as well as for intestinal infections) are a balm for the digestive tract. The malic and tartaric acids of the apple not only make the apple more digestible, but also, serve as a digestive aid for other foods. Perhaps this is why apple confections are such popular desserts among gluttons.
Apples are a specific remedy for liver derangements, including gout and jaundice. An apple eaten at bedtime may relieve insomnia in those cases where the sleeplessness is due to digestive weakness. The apple is one of the richest sources of soluble fiber which helps to prevent sharp blood-sugar swings, and so, is useful in controlling diabetes and hypoglycemia. Soluble fiber also helps to lower elevated cholesterol levels. Apples are beneficial for tooth and gum problems, reduce bowel inflammation, accelerate weight loss among those needing to lose weight, and lower the risk of heart disease and diabetes.
Apples have been a central component of my diet for more than 40 years. I eat 3 apples per day. I begin each day with a pre-workout snack of (all organically grown ingredients) freshly made apple sauce (To make a batch of raw apple sauce, add to blender: 3 to 4 (depending on size) chopped, organic raw apples + ½ tsp. organic ginger powder + 1 to 1.5 cups of organic, unpeeled dried apples (soaked overnight to soften) + 2 Tbsp. of pure water to aid in the pureeing process; blend for about 1 minute. Store unused apple sauce (in a glass jar) in the refrigerator for future use.), organic chia seeds, organic pomegranate juice powder and organic coconut milk powder.
My breakfast consists of raw apple sauce, chia seeds, coconut flakes, fresh or soaked dried (unsweetened) blueberries or apricots, turmeric extract powder and either raw nuts or raw seeds.
Apples and Increased Longevity

Importantly, regular ingestion of apples has been shown to increase longevity. Polyphenols are a category of plant compounds that occur naturally in fruits, vegetables and herbs. When consumed on a regular basis, polyphenols offer a wide-spectrum of health benefits, including: improved brain function, better digestion, and reduced proneness to heart disease, Type 2 diabetes, and certain types of cancer. Since polyphenols act as antioxidants, they can prevent or neutralize cellular damage initiated by oxidative stress: an imbalance between the production of free radicals and the ability of the body to counteract or detoxify their harmful effects through neutralization by antioxidants.
While many other fruits and vegetables also contain polyphenols, apples are one of the best dietary sources. Of the top 25 fruits consumed in the U.S., apples provide 33% of the polyphenols that Americans consume annually. Eating 100 grams of fresh apple with skins provides a total antioxidant activity equal to 1,500 milligrams of vitamin C.
A 2011 study published in the Journal of Agricultural and Food Chemistry found that when fruit flies were given polyphenols extracted from apples as part of their diet, they lived 10% longer than they normally would have. Also, they were more active and continued to be able to fly at a more advanced age. The researchers found that apple polyphenols increased expression of genes within fruit flies that triggered the endogenous (produced or synthesized within the organism) production of cell-protective antioxidants.2
Fisetin
Notably, apples contain a particular polyphenol called fisetin, the regular ingestion of whichresearchers believe may be one of the keys to living a long life. A study published in the journal EbioMedicine found that fisetin is a senotherapeutic (lessens the symptoms of aging) substance that extends health and lifespan.3
Cellular senescence is a process that results from a variety of stresses and is characterized by a state of irreversible growth arrest, and the cessation of cell division. Senescent cells accumulate during aging and have been demonstrated to play a causal role in driving aging and age-related diseases. Of 10 flavonoids tested in the fisetin study, fisetin was the most potent senolytic (eliminates senescent cells from the body). Fisetin reduced senescence markers in multiple tissues. When the researchers administered fisetin to older mice, it restored tissue homeostasis, reduced age-related pathologies, and extended median and maximum lifespan.
Apples and Cancer-Prevention

In addition to fisetin, apples provide high doses of several powerful antioxidants with anticancer properties, including phloridzin, chlorogenic acid, quercetin, caffeic acid and proanthocyanidins.
A 2008 study at Cornell University, found that when an apple extract was fed to healthy rats, it prevented breast cancer. In rats that had breast cancer, it reduced metastasis. According to researcher Rui Hai Liu, M.D., Ph.D.: “Not only did animals treated with apple extract have fewer tumors overall, the tumors were smaller, less likely to be malignant and grew more slowly when compared with tumors in the untreated animals.”4
Other animal studies have shown that compounds found in apples inhibit the growth of colon and liver cancer cells.
Apples are actually the most researched fruit regarding cancer prevention. Multiple population studies have shown that the regular ingestion of apples (as few as 1 apple per day) reduces the risk for lung cancer, breast cancer, pancreatic cancer, non-Hodgkin lymphoma, liver cancer and colon cancer. The bioactive compounds within apples exert powerful anti-proliferative (antigrowth) effects in the body. Research has found that eating apple skin extract lowers the risk of liver cancer in rats by around 57%.5
Oligosaccharides
Importantly, regarding colon cancer, most polyphenol antioxidants are digested and absorbed into the blood before reaching the colon. However, apples also contain a class of compounds called oligosaccharides, which provide a wide range of health benefits.
Oligosaccharides are a type of carbohydrate composed of several monosaccharides, or simple sugars, linked together in a chain. Unlike an apple’s other antioxidants, oligosaccharides are not easily digested or absorbed. Serving as a prebiotic (a non-digestible food ingredient that promotes the growth of beneficial microorganisms in the intestines), oligosaccharides are not easily digested or absorbed. Roughly 90% of oligosaccharides make it intact to the colon. Ultimately, they are fermented by probiotic bacteria, thus, promoting a healthy gut microbiome.
Oligosaccharides can improve immunity, decrease cholesterol and triglyceride levels, enhance digestive health, improve blood sugar regulation, and increase weight loss in those who need to lose weight. In recent years, oligosaccharides have become the subject of numerous studies as they have certain advantages over other natural antioxidants including better biocompatibility. They have been evaluated for their antioxidant activities as well as their potential to serve as antitumor medicines.6
Apples and Heart Health

A 2020 article in Critical Reviews in Food Science and Nutrition based on 16 studies regarding apple consumption, described a wide spectrum of heart-related benefits. According to the article, consuming as few as one medium apple a day has the potential to reduce hypertension, cholesterol, and inflammation ─ three of the primary factors in heart disease.
An observational study is based purely on what the researcher observes, without any manipulation of research subjects (no separate control and treatment groups). In 8 observational studies, whole-apple intake was associated with a reduced risk of cardiovascular disease mortality, ischemic heart disease mortality, stroke mortality, all-cause mortality, and severe abdominal aortic calcification, as well as with lower C-reactive protein concentrations. The level of C-reactive protein, made by the liver, increases when there’s abnormal inflammation in the body.
In a randomized controlled trial, researchers decide randomly as to which participants in the trial receive a given treatment and which receive a placebo. In 8 randomized trials, whole-apple consumption was found to reduce total cholesterol, low-density lipoprotein (LDL) cholesterol, systolic blood pressure, pulse pressure, plasma inflammatory cytokines (a type of protein secreted by certain cells involved in initiating an inflammatory response), and C-reactive protein. It also increased high-density lipoprotein (HDL) cholesterol and improved endothelial function. In the body’s arterioles (the small arteries that precisely regulate the flow of blood to the tissues), the endothelial cell layer (the cells that line the interior surface of blood vessels and lymphatic vessels) maintains the proper dilation and constriction of the blood vessels.
The authors of the article concluded that “these results, support the regular consumption of whole apples as an aid in the prevention of cardiovascular disease.”7
Apples are a rich source of pectin, a water-soluble fiber that lowers blood cholesterol levels by inhibiting its absorption in the gut. Notably, given that obesity is a leading risk factor in the development of cardiovascular disease, pectin expands in the stomach, thus, reducing the tendency to over-eating via an increasing satiety. Quercetin has also been linked to increased heart health by lowering blood pressure.
Also, various flavonoids in apples help prevent the oxidation of LDL-cholesterol (one of the central factors in the progression of cardiovascular disease) and reduce the arterial inflammation that can trigger a heart attack.
Some evidence suggests that eating apples can help lower blood sugar levels, and thus, protect against diabetes In one study in 38,018 women, eating 1 or more apples per day was linked to a 28% lower risk of developing type 2 diabetes.8
A hamster study found that apple ingestion can reduce total cholesterol levels and lead to drastic reductions of 48% in plaque buildup inside the arteries.9
A human study in Finland showed that those who consumed more than 1.9 ounces (54 grams) of apples per day were at a significantly lower risk of developing heart disease. The risk of mortality from heart disease was reduced by 43% lower in women and 19% in men.10
Quercitin: Cancer, Alzheimer’s Disease, and COVID Infection
Apples are a rich source of flavonoids ─ a type of polyphenol responsible for the pigments in plants. Flavonoids are most concentrated in the apple peel. The apple is the only fruit to contain the flavonoid phloridzin, which studies suggest increases bone density and reduces the risk of osteoporosis. Apples also contain boron, an essential mineral that strengthen bones.11
Apples are one of the richest sources of quercetin, a flavonoid that is widely distributed among plants and found commonly in daily diets, predominantly in fruits and vegetables. Quercetin has been shown to exert notable medicinal effects and promising therapeutic potential.
An average sized apple contains about 4.4 milligrams of quercetin for every 100 grams of apple. Therefore, a medium-sized apple of roughly 150 grams may contain as much as 10 milligrams of quercetin ─ a significant quantity.
Vitamin C is perhaps the most well-known antioxidant. While an apple contains vitamin C, it accounts for only a small percentage of the fruit’s total antioxidant activity. Instead, quercetin, rather than vitamin C, is its leading antioxidant.
Note: Quercetin supplements are much more effective when taken in conjunction with vitamin C and bromelain (an enzyme derived from pineapples). Vitamin C activates quercetin activity and bromelain aids its absorption. Bromelain is also an anti-viral agent and also reduces a tendency to the formation of abnormal blood clots.
Cancer
Quercetin, a type of flavonoid (plant pigment) that occurs in relatively large amounts in apples, exerts chemopreventive effects in the body. A chemopreventive agent is a compound, either natural or synthetic, that prevents, reverses, or blocks the development of invasive cancer. Quercetin can trigger tumor regression and begin the process of apoptosis (programmed cell death).12 Absent apoptosis, cells tend to multiply at a higher than normal rate and develop into cancerous growths.
COVID-19 Infection

Quercetin is a natural antihistamine and anti-inflammatory flavonoid that boosts the immune system and helps control viral replication. Significantly, quercetin has an important relationship with the essential mineral zinc. Zinc modulates the activity of numerous cellular signaling and metabolic pathways. Dietary plant polyphenols, such as the flavonoids quercetin and epigallocatechin-gallate, not only act as antioxidants but also as signaling molecules. Importantly, the activities of numerous enzymes involved in cellular signaling and metabolism that are supported by quercetin are zinc-dependent.
The crucial nexus here is that quercetin serves as a zinc ionophore – a substance that transports zinc across the membrane that surrounds a cell into its interior. The ionophore activity of dietary polyphenols (such as quercetin) raises intracellular zinc levels, thus, enhancing many of zinc’s biological actions.13
Notably, regarding COVID-19, zinc exerts potent antiviral actions. Zinc slows down the replication of coronavirus through inhibition of its RNA polymerase enzyme. Zinc deficiency is linked to poor prognosis in COVID-19 patients and clinical trials with zinc demonstrate better clinical outcomes. The zinc ionophore quercetin has been shown to increase the anti-viral potency of zinc. 14 15
This is why, during the COVID-19 pandemic, the combination of zinc and quercetin supplementation was central to the prevention and treatment protocols suggested by those who practice natural medicine. As noted above, research has demonstrated that quercetin enables zinc to fully exert its proven antiviral action. Relevant regarding the treatment of COVID-19 infection, quercetin may also lower inflammation, help clear mucus from the respiratory pathways, prevent ventilator-induced damage and generally support immune system function.
Alzheimer’s Disease

Alzheimer’s disease is currently ranked as the sixth leading cause of death in the United States. 10% of individuals greater than 65 years of age have Alzheimer’s disease and this increases 25% more with individuals greater than 85 years. Early onset of the disease consists of memory loss and forgetting recent conversations and it will develop into severe memory loss.
This neurological disorder causes the death of brain cells, resulting in memory loss and cognitive decline in which the first symptoms are mild and gradually become more severe.
There is increasing scientific evidence that flavonoid-rich foods can beneficially influence normal cognitive function. A growing number of flavonoids have been shown to inhibit the development of Alzheimer disease-like pathologies, and to be able to reverse cognitive deficits.
According to a new study published in the American Journal of Clinical Nutrition, high long-term intake of flavonoid-rich foods, such as apples, berries, etc., is associated with lower risk of Alzheimer’s disease and related dementias.
The beneficial actions of flavonoid-rich foods appear to be mediated by direct interactions between flavonoids (and their metabolites) and various cellular and molecular targets, including signaling pathways and blood-flow to the brain and via initiation of neurogenesis (the growth and development of new nerve cells) in the hippocampus (a part of the brain involved in forming, storing, and processing memory).
An additional mechanism by which flavonoids may delay the initiation of and/or slow the progression of Alzheimer’s-like pathology (and related neurodegenerative disorders), include the potential to inhibit neuronal (nerve cell) apoptosis (programmed cell death initiated by biochemical instructions in the cell’s DNA) triggered by free radical activity (i.e., oxidative stress) and inflammation. In concert, these flavonoid actions help maintain the number and quality of synaptic connections in key brain regions and, thus, help prevent the progression of neurodegenerative pathologies, and preserves or enhances cognitive functions. 16 17
Several studies have shown that quercetin protects neurons from oxidative damage while reducing lipid peroxidation.18 Additionally, it inhibits the fibril formation of beta amyloid proteins. Alzheimer’s disease is characterized by deposits on neurons that consist of a dense proteinaceous core, composed primarily of beta-amyloid proteins.
Amyloid plaques consist of abnormal proteins and fragments of nerve cells that are attached to other nerve cells. When a nerve cell dies, the amyloid protein is embedded in the cell membrane and when it breaks off, a fragment of the protein is still present, and it builds up in the brain. It’s the destruction and death of the nerve cells and the deposits of the protein on the membrane that causes memory failure, personality changes and carrying out activities of daily living.
Quercitin also counteracts cell lysis (the rupture of the cell membrane resulting in the release of cell contents, and the subsequent death of the cell) and inflammatory cascade pathways. An inflammatory cascade features a series of immune reactions, triggered by a harmful stimulus (e.g., injury, infection, etc.), intended to protect and heal affected tissues. The cascade involves the release of various chemical mediators (e.g., cytokines) that regulate blood-flow, cell migration, and tissue breakdown and repair.
While right action taken by the immune system, inflammatory cascades, which can occur anywhere in the body, and can (especially in someone who is sedentary, eats a nutrient-deficient diet, and whose lifestyle otherwise violates the Law of Nature regarding health and disease) persist too long, supersede constructive limits and elicit pain, swelling, scarring, and/or organ dysfunction. Once an inflammatory cascade begins in the brain of an unhealthy individual, its momentum becomes inertial.
Quercetin has demonstrated antioxidant, anti-inflammatory, blood sugar-, and blood fat-lowering activities, all of which suggest it has therapeutic potential against diabetes and Alzheimer’s disease (AD). A study published in Nature, identified several potential molecular mechanisms by which quercetin can simultaneously interfere with diabetes and Alzheimer’s disease progression. Among these, researchers found suppression of MAPK (mitogen-activated protein kinase) signaling (a chain of proteins within a cell that communicates a signal from a receptor on the surface of the cell to the DNA within its nucleus) was considered to be the most promoting strategy. The MAPK signaling pathway is essential for the regulation of many cellular processes, including inflammation, cell stress response, cell differentiation, cell division, cell proliferation, metabolism, motility and apoptosis. The role of the MAPK pathway in cancer, immune disorders and neurodegenerative diseases is well recognized.19
Dr. Berkowsky’s Delicious, Nutrient-Packed, Fresh Apple Sauce + Almond Butter Breakfast Recipe
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References
1. Jie Sun and YiFang Chu. Antioxidant and Antiproliferative Activities of Common Fruits. Journal of Agricultural and Food Chemistry. 2003; 50(25):7449-54.
2. Cheng Peng, Ho Yin Edwin Chan, et al. Apple Polyphenols Extend the Mean Lifespan of Drosophila melanogaster. J. Agric. Food Chem. 2011, 59, 5, 2097–2106.
3. Yousefzadeh, Matthew J. Fisetin is a senotherapeutic that extends health and lifespan. EbioMedicine. 2018 Oct; 36:18-28.
4. Jie Sun and Rui Hai Liu. Apple phytochemical extracts inhibit proliferation of estrogen-dependent and estrogen-independent human breast cancer cells through cell cycle modulation. J Agric Food Chem. 2008 Dec 24; 56(24):11661-7.
5. Linda Nezbedova, et al. Onco-Preventive and Chemo-Protective Effects of Apple Bioactive Compounds. Nutrients. 2021 Nov; 13(11): 4025.
6. Feng Xiong, et al. Characterization, Antioxidant and Antitumor Activities of Oligosaccharides Isolated from Evodia lepta (Spreng) Merr. by Different Extraction Methods. Antioxidants. 2021, 10(11), 1842.
7. Berner Andrée Sandoval-Ramírez, et al. The effects and associations of whole-apple intake on diverse cardiovascular risk factors. A narrative review. Crit Rev Food Sci Nutr. 2020; 60(22):3862-3875.
8. Maria de Olievera, et al. Weight Loss Associated With a Daily Intake of Three Apples or Three Pears Among Overweight Women. Nutrition. Volume 19, Issue 3, March 2003, 253-256.
9. Kelly Décordé, et al. Phenolics from purple grape, apple, purple grape juice and apple juice prevent early atherosclerosis induced by an atherogenic diet in hamsters.
Mol Nutr Food Res. 2008 Apr; 52(4):400-7.
10. P Knekt, et al. Flavonoid intake and coronary mortality in Finland: a cohort study. BMJ. 1996 Feb 24; 312(7029):478-81.
11. C Puel, et al. Prevention of bone loss by phloridzin, an apple polyphenol, in ovariectomized rats under inflammation conditions. Calcif Tissue Int. 2005 Nov; 77(5):311-8.
12. Hehua Wang, et al. Mechanisms of cancer-killing by quercetin; A review on cell death mechanisms.
Anticancer Agents Med Chem. 2023 Jan 20.
13. Husam Dabbagh-Bazarbachi, et al. Zinc ionophore activity of quercetin and epigallocatechin-gallate: from Hepa 1-6 cells to a liposome model. J Agric Food Chem. 2014 Aug 13; 62(32):8085-93.
14. Aartjan J W te Velthuis, et al. Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS Pathog. 2010 Nov 4; 6(11):e1001176.
15. Love Panchariya and Wajahat Ali Khan. Zinc2+ ion inhibits SARS-CoV-2 main protease and viral replication in vitro. Chem Commun (Camb). 2021 Sep 30; 57(78):10083-10086.
16. Roger J. Williams and Jeremy P.E. Spencer. Flavonoids, cognition, and dementia: Actions, mechanisms, and potential therapeutic utility for Alzheimer disease.
Free Radical Biology and Medicine. Volume 52, Issue 1, 1 January 2012: 35-45
17. Esra Shishtar, et al. Long-term dietary flavonoid intake and risk of Alzheimer disease and related dementias in the Framingham Offspring Cohort. The American Journal of Clinical Nutrition, Volume 112, Issue 2, August 2020: 343–353.
18. Haroon Khan. Neuroprotective Effects of Quercetin in Alzheimer’s Disease. Biomolecules 2020, 10(1): 59.
19. Guoxiu Zu. Mechanism of quercetin therapeutic targets for Alzheimer disease and type 2 diabetes mellitus. Nature, 2021 November 25.