Oranges as Medicine

This article on oranges is a chapter from my book Cancer Cured.  If you find it helpful, please support my work and buy my book on Amazon.

Sweet, powerfully refreshing and bursting with flavor, it’s no surprise that oranges are one of the most popular fruits in the world.  Most people are aware that oranges are a potent source of vitamin C, but there are a number of other nutrients within an orange that boost its medicinal value considerably.

In this chapter, we will investigate the therapeutic potential of citrus flavonoids, modified citrus pectin, vitamin C and orange juice on cancer and overall health.

Citrus Flavonoids

Flavonoids are naturally occurring substances found in fruits, vegetables, teas and wines that are responsible for the diversity of colors produced by plants.1  Epidemiological studies have shown that dietary consumption of flavonoids can reduce the risk of cardiovascular disease,3 asthma, type 2 diabetes, heart disease, prostate cancer and lung cancer.4

More than 60 flavonoids have been identified in orange fruit, making them one of the most concentrated and readily available sources of flavonoids.366  A 2003 study from the UK found that a Sicilian variety of orange called Tarocco had higher concentrations of citrus flavonoids than 6 other orange varieties tested.Interestingly, flavonoids are found more abundantly in the peel than in the pulp of citrus fruit.2

Some examples of citrus flavonoids include naringin, naringenin, diosmin, hesperetin, hesperidin, quercetin, tangeretin, nobiletin.  In this section we will investigate three of them.

Citrus Flavonoids Vs. Cancer

One of the methods used by scientists to test the therapeutic value of nutrients or drugs against cancer is to add them to a test tube containing cancer cells and observe the effects.  Testing cancer cells outside of living organisms in this way is called in vitro.  Sometimes effects observed in vitro are not the same as inside living organisms, or in vivo, but many times they are, as you will see.


In vitro studies have confirmed naringin can inhibit the growth of stomach,9 cervical,12 breast,14 and colon cancer cells,11 the spread of brain7,8 and bone cancer cells,10 and trigger cancer cell death (apoptosis) in colon,11,17 pancreatic,17 stomach,17 cervical,12,13,17 liver17 and breast cancer cells.14,17

Another popular method used by scientists to determine the value of nutrients or drugs against cancer is inducing cancer in animals – usually by injecting carcinogenic chemicals into them – and then administering the treatment and observing the outcome.

In vivo studies have confirmed naringin can inhibit the growth of colon,18 oral,19 lung20 and connective tissue tumors,16,17 the spread of skin tumors20and trigger apoptosis in colon tumors.18

A Closer Look…

  • In 2012, scientists from Sao Paulo, Brazil, investigated the effects of naringin on rats bearing connective tissue cancer. Results showed that a 25mg/kg dose of naringin administered daily for 50 days inhibited tumor growth by 75%.  Naringin also increased survival and notably, “two rats presented complete tumor regression.”16

One of the most exciting experiments on naringin was conducted in 2016 by Chinese researchers, who added naringin to skin cancer cells to determine its impact on cellular energy metabolism.  One of the key changes in the metabolism of cancer cells is increased production of lactic acid, and not only did naringin inhibit lactic acid production in the skin cancer cells, but it also completely reversed them back into normal cells.  “In summary, we demonstrated that naringin inhibits the malignant phenotype of A375 cells.” they concluded.15

Perhaps best of all, the beneficial effects of naringin can be obtained “without adverse side effects.” 59

Normally, once a ‘drug’ has proven itself in vitro and in vivo, it would move on to human testing in clinical trials, but since the average cost of phase 1 clinical trial in the United States ranges from $1.4 million to $6.6 million dollars;198 and since natural substances found in foods can’t be patented or sold by drug companies, this type of research doesn’t often receive funding and is thus rarely performed.

Many times, the only reason in vitro and in vivo studies on food nutrients are funded is so drug companies can find medicines that work and then attempt to replicate similar chemicals to patent and sell.


A 2015 study identified naringenin as one of 10 therapeutic agents “that may warrant further investigation to target the tumor microenvironment” for preventing and treating cancer.”64

In vitro experiments have established naringenin can inhibit the growth of breast,65,73 stomach,71 colon,66,73 skin,68,76 leukemia75 and liver cancer cells,67,77 the spread of breast,65 liver,67 skin,68 bladder,69 pancreatic,70 and stomach cancer cells,71 and trigger apoptosis in liver,67,77 stomach,71 colon,72,73 breast,73,74 leukemia75 and skin cancer cells.76

Animal experiments have verified naringenin can inhibit the growth of oral,19 stomach,78 lung81 and brain tumors,80 prevent the spread of breast tumors79 and trigger apoptosis in brain tumors.82

Synergistic enhancement of the anti-cancer effects of naringenin can be obtained by combining it with either curcumin83 or vitamin E,84 and one study reports that nano-encapsulated naringenin exhibits “significantly higher” antioxidant and anticancer properties than naringenin in free form.86

Naringenin has a “promising safety profile”133 and remarkably, it maintains its cancer-killing effects even in the presence of the environmental toxin bisphenol A.85


In vitro, hesperidin can inhibit the growth of breast,134,135 immune,138 leukemia,140,141 and lung cancer cells,143  the spread of skin cancer cells,136 and trigger apoptosis in breast,135,144 immune,138 colon,139 leukemia,140,141 liver137,142 and lung cancer cells.143

Animal studies have confirmed hesperidin can inhibit the growth of colon,145 lung,146 bladder,147 oral,148,149 throat150 and stomach tumors,151 and trigger apoptosis in stomach151 and colon tumors.152

One study compared the medicinal potencies of a number of citrus flavonoids and found that hesperidin exerted a more powerful anti-cancer effect than neohesperidin, naringin and naringenin.137  With that in mind, Tunisian researchers reported in 2016 that concentrations of hesperidin were greater in organically-grown oranges than in oranges grown conventionally.6

A safety study from 1990 fed rats dietary concentrations of 0%, 1.25% or 5% methyl hesperidin for two years and concluded that the substance “lacked any carcinogenicity” in rats.193

Additional Health Effects


  • Naringin exerts a “robust antibacterial effect”21
  • Hesperidin inhibits growth of bifidobacteria153


  • Naringin neutralizes the toxic effects of herbicide paraquat22
  • Naringin prevents kidney and liver damage from acetaminophen23 and sodium arsenite24
  • Naringin prevents chemotherapy-induced kidney25 and lung damage26
  • Naringin reverses side effects of HIV medication29,30
  • Naringenin prevents damage from lead108 and endotoxin87
  • Hesperidin prevents chemically-induced kidney damage155-158
  • Hesperidin prevents chemotherapy-induced liver damage161


  • Naringin28 and naringenin93 inhibit infection by sindbis virus28
  • Naringenin reduces hepatitis C virus secretions from infected cells by 80%92
  • Hesperidin prevents replication of influenza A virus162
  • Hesperidin inhibits infection by canine distemper virus163 and rotavirus164
  • Hesperidin inhibits combined viral-bacterial infections165


  • Naringin prevents inflammation associated with arthritis31-34
  • Naringenin prevents inflammatory pain in mice94,95
  • Hesperidin prevents chemically-induced arthritis154,166,167


  • Naringin significantly reduces coughing (associated with a type of asthma that causes chronic coughing)63

Bone Health:

  • Naringin prevents the destruction of cartilage38
  • Naringin,35,36 naringenin96-99 and hesperidin168-170 prevent bone loss and accelerate bone formation

Brain Health:

  • Naringin reverses chemically-induced memory deficits39-41,47
  • Naringin improves brain function in mice with Alzheimer’s disease42,43
  • Naringin prevents brain degeneration in rats with Parkinson’s disease44-46
  • Naringin prevents chemically-induced seizures48
  • Naringenin reduces anxiety caused by lead poisoning89
  • Naringenin prevents brain damage caused by neurotoxins90 and iron102
  • Naringenin prevents Alzheimer’s disease100
  • Naringenin improves learning and memory in rats with Alzheimer’s disease101
  • Naringenin prevents cognitive decline in rats with Parkinson’s disease103
  • Hesperidin prevents brain damage from pesticides,171 heavy metals,172 and other poisons174
  • Hesperidin prevents cognitive impairment in mice with Alzheimer’s disease173
  • Hesperidin prevents brain damage caused by ionizing radiation188


  • Naringenin prevents toxic acrylamides from forming in food during high-heat cooking132

Dental Health:

  • Naringin remineralizes root caries (cavities) in teeth37


  • Naringenin produces antidepressant-like behavior in rats106,107
  • Naringenin105 and hesperidin175-177 exert potent antidepressant effects


  • Naringenin chelates lead from the body108


  • Naringin prevents scarring of the heart caused by diabetes49
  • Naringenin prevents kidney damage caused by diabetes52,109
  • Naringenin improves glucose metabolism110,111
  • Naringin improves insulin sensitivity50,51
  • Hesperidin reduces diabetes and its complications178

Digestive Health:

  • Naringenin an effective treatment for inflammatory bowel disease120,121
  • Naringenin prevents defects of the intestinal barrier122


  • Naringin in combination with treadmill exercise is more effective at increasing bone strength and density than either therapy alone53
  • Hesperidin synergistically enhances the health benefits of exercise179

Eye Health:

  • Naringenin eye drops prevent chemically-induced retinal damage91
  • Hesperidin prevents eye damage caused by chemotherapy159

Food Production:

  • Naringin and Hesperidin fed to chickens elevates antioxidant levels in chicken meat; are “important additives for both the consumer and the industry.”27


  • Drynaria quercifolia (a plant containing naringin) alleviates painful inflammatory conditions, like headache54
  • Hesperidin may be useful for treating migraines180


  • Naringin55 and hesperidin191 accelerate wound healing

Heart Health:

  • Naringin56 and naringenin113 prevent arterial plaque formation
  • Naringinen reduces arterial stiffness112
  • Naringenin prevents thickening of the heart muscle114

Immune System:

  • Naringenin boosts the immune system115,116
  • Naringenin significantly enhances anti-cancer immunity117-119
  • Hesperidin enhances immune systems of mice181 and irradiated mice189
  • Hesperidin enhances immune systems of broiler chickens182


  • Naringin significantly decreases fat mass57,59
  • Naringin prevents formation of new fat tissue58
  • Naringenin reduces body fat and suppresses weight gain123-125
  • Hesperidin improves lipid metabolism in humans183,184

Radiation protective:

  • Naringin protects skin from ultraviolet B radiation61
  • Naringin60 and naringenin126 prevent genetic damage caused by ionizing radiation
  • Naringenin prevents skin aging and wrinkle formation caused by ultraviolet B radiation127-129
  • Naringenin added to conventional sunscreen reduces its toxicity130
  • Hesperidin reduces damage caused by whole-body gamma ray irradiation185
  • Hesperidin prevents ultraviolet B radiation damage186,187

Sexual Health:

  • Naringenin aids the process of conception104
  • Naringenin prevents testicle damage caused by insecticides88
  • Hesperidin prevents testicle and sperm damage caused by chemotherapy160

Skin Health:

  • Naringin62 and hesperidin192 promote the production of skin-protective melanin
  • Naringenin “should be introduced into cosmetic products as natural tanning agents.”131


  • A mixture of citrus flavonoids Hesperidin, Troxerutin, and Diosmin applied to hemmorhoids reduces pain, bleeding and swelling in humans190

Modified Citrus Pectin

Pectin is a complex of sugar molecules (polysaccharide) heavily concentrated in the pulp and peel of citrus fruit.  Because of its gelling properties, pectin is a traditional ingredient used for making marmalades and jams.

Pectin’s long-branched chains of polysaccharides make it virtually indigestible by humans, but researchers have discovered ways to modify pectin so it can be easily absorbed into the blood stream.  Once in the bloodstream, modified citrus pectin (MCP) has proven useful for treating a number of conditions, including cancer.317  Although heat treatment and pH modifications are commonly used to create modified citrus pectin,315 high-intensity ultrasound is also effective and is said to be more ‘environmentally friendly.’316

“The more we learn about MCP, the more impressive it becomes,” said Dr. Isaac Eliaz. “With its ability to control aggressive cancers, reduce inflammation, enhance immunity, chelate heavy metals and work synergistically with a variety of chemotherapeutic agents, it has earned an important role within anti-cancer and chronic disease protocols.”367

Modified Citrus Pectin vs. Cancer

Scientists have observed modified citrus pectin prevent the growth of prostate cancer cells320,322 and trigger apoptosis in lung,321 liver,321 prostate322 and eight other types of cancer cells.323

Co-administration of modified citrus pectin with two herbal products have revealed synergistic inhibitory effects on the spread of breast and prostate cancer in vitro.324 Modified citrus pectin can also eliminate chemotherapy resistance325 and increase the apoptosis-inducing effects of chemotherapy in cell cultures.326

Modified citrus pectin can prevent the growth of skin327 and sarcoma tumors in mice; including a 51% reduction in tumor size and increased survival compared to control mice.323  Another study reported a 70% reduction in colon tumor size in mice after 20 days of MCP treatment.332  Also in animals, the spread of breast,328 prostate,329 skin330 and colon tumors can be inhibited by as much as 90% using modified citrus pectin.331

Scientists from the Harry S. Truman Memorial Veteran’s Hospital in Missouri discovered that MCP prevents cancer metastasis by inhibiting circulating tumor cells from adhering and establishing themselves onto distal body tissues.318  Another mechanism behind MCP’s therapeutic effects is the inhibition of a substance called Galectin-3, which is involved in inflammation, fibrosis, heart disease, stroke and cancer.319

Studies report modified citrus pectin has no adverse side effects,339 including one study in which 15 grams MCP was administered daily to humans for 12 consecutive months.340

Additional Health Effects


  • MCP prevents liver fibrosis334
  • MCP prevents kidney injury335
  • MCP prevents damage caused by endotoxin336


  • MCP is “a therapeutic approach for the treatment of inflammatory arthritis” 337


  • MCP dramatically increases urinary excretion of arsenic, cadmium and lead in humans338
  • MCP safely and dramatically detoxifies lead from children339
  • MCP reduces toxic heavy metal burden in humans by an average of 74%340

Heart Health:

  • MCP “may represent a new promising therapeutic option in heart failure”341
  • MCP decreases cardiovascular fibrosis and inflammation342,343,344
  • Galectin-3 inhibition “causes decreased atherosclerosis”345

Immune System:

  • MCP enhances anti-cancer immunity346


  • MCP reduces inflammation and pain after spinal nerve injury333


  • MCP prevents production of new fat tissue347

Vitamin C

Although vitamin C (aka ascorbic acid or ascorbate) wasn’t officially discovered until 1928 by Hungarian biochemist Albert Szent-Gyorgyi,194 the manifestations of its deficiency, known as scurvy,195 were first documented by the physician Hippocrates in ancient Greece (460BC-370BC).368  In 1945, scientists from the University of Wisconsin found that when they deprived monkeys of vitamin C for just a few weeks, various dental issues including bleeding gums, loosening of the teeth and the formation of heavy tartar deposits were induced.196

The effects of supplemental vitamin C are highly-dependent on the dose administered.  In low doses, vitamin C behaves as an anti-oxidant, helping the body neutralize toxins and eliminate waste products.  And in high doses, vitamin C acts as a pro-oxidant that can selectively target unhealthy and even cancerous cells.197 High-doses of intravenous vitamin C have been used to treat cancer since the 1970s.200

Vitamin C vs. Cancer

One thing cancer patients all have in common is significantly depleted levels of vitamin C.222  Remarkably, some researchers have said that vitamin C might be the most important nutritional factor needed by the body to resist cancer; “There is increasing recognition that resistance to cancer depends, to a certain extent, upon the availability of certain nutritional factors, of which ascorbic acid appears to be the most important,” wrote scientist Ewan Cameron in 1982.201

An epidemiological study of people in Northern Italy reported that vitamin C intake has “possible protective activity” against skin cancer202 and greater consumption of antioxidants was associated with less aggressive prostate cancer in the United States.203  A 2014 systematic review by Chinese researchers concluded that low doses of vitamins, specifically vitamins A, C and E, can significantly reduce the risk of stomach cancer.204

In vitro studies have confirmed vitamin C can trigger apoptosis in colon,206,207,214 breast,207 skin,208 blood,209 bone marrow,209 Ehrlich acites carcinoma,205 melanoma220 and four types of malignant mesothelioma cancer cells.213

Co-administration of vitamin C and vitamin B2 can synergistically enhance apoptosis in multiple types of cancer cells.210  Vitamin C loaded into tiny bubbles of fat (lipid nanoparticles) was shown to enter into cells more efficiently than free vitamin C219 and vitamin C affixed to nano-sized polymer carriers has been shown to trigger apoptosis in brain cancer cells.218

In animals, vitamin C can prevent the growth of lung,211 skin,211 ovarian,212 pancreatic,212 brain,212 malignant mesothelioma,213 colon214 and sarcoma tumors,215 and can trigger apoptosis in liver tumors.216  A nutrient mixture containing lysine, vitamin C, proline, green tea extract and other micronutrients fed to tumor-bearing mice “demonstrated a potent inhibition of [cervical] tumor growth.”217

A Closer Look…

  • An American group of scientists from Kansas administered 500mg/kg/day sodium ascorbate to liver tumor-bearing guinea pigs in 2006. Results showed that “Subcutaneous injections of ascorbate (500 mg/kg/day) inhibited tumor growth by as much as sixty-five percent, with oral supplementation reducing it by roughly fifty percent.” 216

In 1994, researchers from the Oregon Institute of Science and Medicine induced tumors in mice and treated them with high-doses of vitamin C along with variations in diet.  Results showed that survival could be increased by up to 20-times simply by adjusting the animal’s nutritional intake.221

Two-time Nobel Prize winner Linus Pauling and surgeon Ewan Cameron administered 10 grams/day of vitamin C to terminal cancer patients in 1976 and found that survival was increased “more than 4.2 times” compared to patients who weren’t given vitamin C.222  Other studies have confirmed vitamin C can increase survival and significantly improve the quality of life of terminal cancer patients.223-225

How does vitamin C exert its beneficial effects?  When blood levels of vitamin C are maintained at a consistently high level, it is absorbed into cancerous tissue where it produces hydrogen peroxide that kills cancer cells.199


Thanks to the work of Dr. Frederick R. Klenner, it has been known for over 70 years that vitamin C doses as high as 300,000mg (300 grams) per day in humans are safe and modern research has confirmed this finding.205,209,212,224,225,235,260

A Korean study from 2007 acknowledged that vitamin C “is considered a safe and effective therapy”225 and a 2008 study from the National Institutes of Health found that high-doses of vitamin C displayed “cytotoxicity toward a variety of cancer cells in vitro without adversely affecting normal cells.”212

One thing to be aware of is that vitamin C can increase the absorption of iron,307-309 which in small amounts is essential, but like all heavy metals, becomes toxic in excess311 and can diminish the effectiveness of vitamin C treatment.310  For these reasons, oral supplementation of vitamin C is probably best without food and to lower existing iron levels in the body, iron-chelating substances such as tetracycline, doxycycline, minocycline312 or curcumin369 can be used.

Oral vs. Intravenous

There is some controversy surrounding the efficacy of various vitamin C administration methods.  While Dr. Mark Levine of the NIH claims that “…only injected ascorbate might deliver the concentrations needed to see an anti-tumor effect,”313 Dr. Steve Hickey has said, “it is not clear that intravenous vitamin C necessarily provides an advantage over oral supplements in the treatment of cancer.”314

When the body is given a high enough dose of vitamin C intravenously, much of it goes unused and is excreted in the urine, according to Dr. Hickey.  Furthermore, he makes the case that high-doses of orally administered vitamin C might even be more effective.314

While Dr. Levine claims that maximum blood levels of vitamin C are 200μM/L, Dr. Hickey maintains he has been able to generate blood levels of around 250μM/L with a single 5 gram oral dose of vitamin C and blood levels above 400μM/L with a single oral dose of liposomal vitamin C.314


For many people, a single oral dose of 2 grams of vitamin C will cause a laxative effect and anything more will be eliminated from the body.  Interestingly, bowel tolerance is said to increase dramatically when a person is ill.314  In other words, a person who would normally be able to tolerate only 2 grams might be able to tolerate 100-times that amount when sick.

Maximum blood levels of orally-ingested vitamin C can be achieved by consuming about 3 grams every four hours.  Since vitamin C is only active in the body for a few hours, frequent doses are critical to maintain consistently high blood levels.

Success Stories

Dr. Victor Marcial, radiation oncologist:

“We studied patients with advanced cancer (stage 4). 40 patients received 40,000-75,000 mg intravenously several times a week. These are patients that have not responded to other treatments. The initial tumor response rate was achieved in 75% of patients, defined as a 50% reduction or more in tumor size… Once you start using IV vitamin C, the effect is so dramatic that it is difficult to go back to not using it.”

Linus Pauling, 2x Nobel Prize Laureate:

“I became interested in vitamin C and cancer in 1971 and began working with Ewan Cameron, M.B., Ch.B., chief surgeon at Vale of Leven Hospital in Scotland.  Cameron gave 10 grams of vitamin C a day to patients with untreatable, terminal cancer.  These patients were then compared by Cameron and me to patients with the same kind of cancer at the same terminal stage who were being treated in the same hospital but by other doctors-doctors who didn’t give vitamin C, but instead just gave conventional treatments.  Cameron’s terminal cancer patients lived far longer compared to the ones who didn’t get 10 grams a day of vitamin C. The other patients lived an average of six months after they were pronounced terminal, while Cameron’s patients lived an average of about six years.”

Dr. Irwin Stone, American biochemist, chemical engineer:

“In one case where complete remission was achieved in myelogenous leukemia… the patient took 24-42 gms vitamin c per day… it is inconceivable that no-one appears to have followed this up… without the scurvy, leukemia may be a relatively benign, non-fatal condition.  I wrote a paper… in an attempt to have the therapy clinically tested… I sent it to 3 cancer journals and 3 blood journals… it was refused by all… Two without even reading it.”

Additional Health Effects


  • Vitamin C an antidote for snake venom228
  • Vitamin C a cure for carbon monoxide poisoning233
  • Vitamin C a cure for mushroom poisoning229
  • Vitamin C prevents damage caused by agricultural fungicides230 and insecticides231
  • Vitamin C prevents liver damage caused by dexmedetomidine236
  • Vitamin C prevents damage caused by monosodium glutamate237
  • Vitamin C prevents damage caused by methylmercury,238 formaldehyde239 and endotoxin241,242,245,246,248
  • Vitamin C prevents chemically-induced ulcer formation in rats240
  • Vitamin C prevents septic organ injury in mice243
  • Vitamin C prevents alcohol-induced liver fibrosis in mice244
  • Vitamin C prevents the formation of nitric oxide247
  • Vitamin C prevents kidney249 and liver damage250,251 caused by chemotherapy


  • Vitamin C “kills influenza virus” 252
  • Vitamin C shortens duration of the common cold, pneumonia, malaria and diarrhea infections253
  • Vitamin C suppresses HIV replication by infected cells254
  • Vitamin C successfully treats hepatitis, mononucleosis and pneumonia255
  • Vitamin C successfully treats polio, diphtheria, herpes zoster, herpes simplex, chicken pox, influenza, measles, mumps and viral pneumonia256
  • Vitamin C successfully treats Epstein-Barr virus257
  • Vitamin C resolves all symptoms of Chikungunya fever in two days260


  • Elevated free radicals and oxidative stress found in patients with Rheumatoid Arthritis227

Bone Health:

  • Vitamin C prevents bone loss261
  • Vitamin C improves bone mineral density in postmenopausal women262-264
  • Vitamin C is “a skeletal anabolic agent” 265
  • Vitamin A, C and E decrease risk of hip fracture266

Brain Health:

  • Vitamin C prevents brain damage caused by methamphetamine,267 insecticides268,269 and glutamate270
  • Vitamin C deficiency increases risk of seizures271
  • Vitamin C (and zinc) deficiencies impair the physical and mental growth of children287
  • Vitamin C levels in patients with severe Parkinson’s disease were “significantly lower” 272


  • Vitamin C reduces anxiety levels in highschool students after 14 days of supplementing 500mg276


  • Vitamin C chelates lead from the bloodstream277
  • Vitamin C reduces blood levels of chemical pollutants232


  • Vitamin C reduces fasting blood sugar in diabetics278,280
  • Vitamin C significantly lowers needed insulin dose for blood sugar control279


  • Vitamin C and low-intensity exercise prevent seizures281
  • Vitamin C has anti-seizure effects in rats performing endurance swimming282
  • Vitamin C improves blood flow and oxygen use in muscles283

Food Production:

  • Vitamin C improves growth performance and enhances stress resistance in fish303


  • Vitamin C and Pinus Radiata bark extract ingested for 12 months reduces headache severity and frequency by 50%284


  • Vitamin C accelerates healing235,301
  • Vitamin C enhances cell survival and DNA repair in human fibroblasts exposed to x-rays299

Heart Health:

  • Vitamin C decreases length of hospital stay in patients following cardiac surgery304

Immune System:

  • Vitamin C enhances anti-cancer immunity285,289-292
  • Vitamin C significantly enhances immunity286-288


  • Vitamin C reduces inflammation226


  • Antioxidant-rich diet extends survival of mice exposed to endotoxin234
  • Vitamin C extends lifespan of tetanus patients258,259


  • Vitamin C intake reduces obesity in women293

Radiation protective:

  • Vitamin C prevents damage caused by ionizing radiation294,297,298
  • Vitamin C and vitamin E synergistically prevent damage caused by ionizing radiation295
  • Vitamin C and melatonin synergistically prevent damage caused by ionizing radiation296

Sexual Health:

  • Vitamin C “significantly improves sperm concentration and mobility” 274
  • Vitamin C prevents infertility in rats subjected to forced swimming stress275
  • Vitamin C promotes a healthy pregnancy273


  • Vitamin C prevents spatial memory impairment in rats following sleep deprivation300


  • Vitamin C resolves symptoms of burning mouth syndrome in humans302
  • Vitamin C diminishes microparticle elevations caused by SCUBA diving305
  • Vitamin C prevents complex regional pain syndrome in humans306

Orange Juice

If an orange contains all the medicines we’ve investigated above, then one would expect orange juice to also have substantial therapeutic value.

Orange Juice vs Cancer

Although studies are limited, scientists have investigated the therapeutic effects of orange juice on cancer cell cultures and in animals.  In vitro studies have confirmed orange juice can trigger apoptosis in two types of blood cancer cells.348

In vivo, researchers have experimentally induced tumors in rats and then replaced their water with orange juice to determine its effects.  Results show that orange juice can inhibit the growth of breast,349 colon,350-352 tongue352 and lung tumors,352  and can trigger apoptosis in colon tumors.350

A Closer Look…

  • In 2015, Brazilian researchers incubated two types of blood cancer cells with orange juice – one with the juice of a red-fleshed sweet orange and the other with juice from a blond orange – for 24-hours and observed the results. At the end of the study, both varieties of orange juice were found to induce apoptosis in the blood cancer cells.348
  • Mandarin orange juice was tested on rats induced with three types of cancers in a 2012 Japanese study from the Journal of Biomedicine & Biotechnology. Citrus juices from the satsuma mandarin orange were found to inhibit the formation of chemically-induced colon, tongue and lung tumors in rats.352
  • Canadian scientists from Western University in London, Ontario, chemically-induced breast tumors in rats and fed them orange juice to determine if it could prevent cancer formation. Published in the journal Nutrition and Cancer in 1996, results showed that rats given orange juice “had a smaller tumor burden than controls.” 349

Additional Health Effects


  • Tangerine juice concentrate is effective for “controlling unwanted microbial growth” 353


  • Orange juice consumption results in a “marked antioxidant effect”355,356

Bone Health:

  • Orange juice increases bone strength in rats358
  • Orange juice increases bone mineral density in children and adults357


  • Orange juice prevents exercise-induced hypoxia359
  • Orange juice improves physical performance in overweight women360

Heart Health:

  • Fermented orange juice reduces cardiovascular risk factors361

Immune System:

  • Orange juice enhances the immune system362


  • Orange juice reduces inflammation354


  • Orange juice associated with healthier body composition in adults363
  • Orange juice decreases risk of obesity364
  • Orange juice prevents fatty liver disease365


  1. Patel K, Singh GK, Patel DK. A review on pharmacological and analytical aspects of naringenin. Chin J Integr Med. 2014.
  2. Nakajima VM, Madeira JV, Macedo GA, Macedo JA. Biotransformation effects on anti lipogenic activity of citrus extracts. Food Chem. 2016;197 Pt B:1046-53.
  3. Chanet A, Milenkovic D, Manach C, Mazur A, Morand C. Citrus flavanones: what is their role in cardiovascular protection?. J Agric Food Chem. 2012;60(36):8809-22.
  4. Knekt P, Kumpulainen J, Järvinen R, et al. Flavonoid intake and risk of chronic diseases. Am J Clin Nutr. 2002;76(3):560-8.
  5. Proteggente AR, Saija A, De pasquale A, Rice-evans CA. The compositional characterisation and antioxidant activity of fresh juices from sicilian sweet orange (Citrus sinensis L. Osbeck) varieties. Free Radic Res. 2003;37(6):681-7.
  6. Letaief H, Zemni H, Mliki A, Chebil S. Composition of Citrus sinensis (L.) Osbeck cv «Maltaise demi-sanguine» juice. A comparison between organic and conventional farming. Food Chem. 2016;194:290-5.
  7. Aroui S, Aouey B, Chtourou Y, Meunier AC, Fetoui H, Kenani A. Naringin suppresses cell metastasis and the expression of matrix metalloproteinases (MMP-2 and MMP-9) via the inhibition of ERK-P38-JNK signaling pathway in human glioblastoma. Chem Biol Interact. 2016;244:195-203.
  8. Aroui S, Najlaoui F, Chtourou Y, et al. Naringin inhibits the invasion and migration of human glioblastoma cell via downregulation of MMP-2 and MMP-9 expression and inactivation of p38 signaling pathway. Tumour Biol. 2016;37(3):3831-9.
  9. Raha S, Yumnam S, Hong GE, et al. Naringin induces autophagy-mediated growth inhibition by downregulating the PI3K/Akt/mTOR cascade via activation of MAPK pathways in AGS cancer cells. Int J Oncol. 2015;47(3):1061-9.
  10. Tan TW, Chou YE, Yang WH, Hsu CJ, Fong YC, Tang CH. Naringin suppress chondrosarcoma migration through inhibition vascular adhesion molecule-1 expression by modulating miR-126. Int Immunopharmacol. 2014;22(1):107-14.
  11. Vadde R, Radhakrishnan S, Reddivari L, Vanamala JK. Triphala Extract Suppresses Proliferation and Induces Apoptosis in Human Colon Cancer Stem Cells via Suppressing c-Myc/Cyclin D1 and Elevation of Bax/Bcl-2 Ratio. Biomed Res Int. 2015;2015:649263.
  12. Zeng L, Zhen Y, Chen Y, et al. Naringin inhibits growth and induces apoptosis by a mechanism dependent on reduced activation of NF‑κB/COX‑2‑caspase-1 pathway in HeLa cervical cancer cells. Int J Oncol. 2014;45(5):1929-36.
  13. Ramesh E, Alshatwi AA. Naringin induces death receptor and mitochondria-mediated apoptosis in human cervical cancer (SiHa) cells. Food Chem Toxicol. 2013;51:97-105.
  14. Li H, Yang B, Huang J, et al. Naringin inhibits growth potential of human triple-negative breast cancer cells by targeting β-catenin signaling pathway. Toxicol Lett. 2013;220(3):219-28.
  15. Guo B, Zhang Y, Hui Q, Wang H, Tao K. Naringin suppresses the metabolism of A375 cells by inhibiting the phosphorylation of c-Src. Tumour Biol. 2016;37(3):3841-50.
  16. Camargo CA, Gomes-marcondes MC, Wutzki NC, Aoyama H. Naringin inhibits tumor growth and reduces interleukin-6 and tumor necrosis factor α levels in rats with Walker 256 carcinosarcoma. Anticancer Res. 2012;32(1):129-33.
  17. Kanno S, Tomizawa A, Hiura T, et al. Inhibitory effects of naringenin on tumor growth in human cancer cell lines and sarcoma S-180-implanted mice. Biol Pharm Bull. 2005;28(3):527-30.
  18. Zhang YS, Li Y, Wang Y, et al. Naringin, a natural dietary compound, prevents intestinal tumorigenesis in Apc (Min/+) mouse model. J Cancer Res Clin Oncol. 2016;142(5):913-25.
  19. Miller EG, Peacock JJ, Bourland TC, et al. Inhibition of oral carcinogenesis by citrus flavonoids. Nutr Cancer. 2008;60(1):69-74.
  20. Menon LG, Kuttan R, Kuttan G. Inhibition of lung metastasis in mice induced by B16F10 melanoma cells by polyphenolic compounds. Cancer Lett. 1995;95(1-2):221-5.
  21. Ozçelik B, Kartal M, Orhan I. Cytotoxicity, antiviral and antimicrobial activities of alkaloids, flavonoids, and phenolic acids. Pharm Biol. 2011;49(4):396-402.
  22. Blanco-ayala T, Andérica-romero AC, Pedraza-chaverri J. New insights into antioxidant strategies against paraquat toxicity. Free Radic Res. 2014;48(6):623-40.
  23. Adil M, Kandhare AD, Ghosh P, Venkata S, Raygude KS, Bodhankar SL. Ameliorative effect of naringin in acetaminophen-induced hepatic and renal toxicity in laboratory rats: role of FXR and KIM-1. Ren Fail. 2016;:1-14.
  24. Adil M, Kandhare AD, Visnagri A, Bodhankar SL. Naringin ameliorates sodium arsenite-induced renal and hepatic toxicity in rats: decisive role of KIM-1, Caspase-3, TGF-β, and TNF-α. Ren Fail. 2015;37(8):1396-407.
  25. Chtourou Y, Aouey B, Aroui S, Kebieche M, Fetoui H. Anti-apoptotic and anti-inflammatory effects of naringin on cisplatin-induced renal injury in the rat. Chem Biol Interact. 2016;243:1-9.
  26. Turgut NH, Kara H, Elagoz S, Deveci K, Gungor H, Arslanbas E. The Protective Effect of Naringin against Bleomycin-Induced Pulmonary Fibrosis in Wistar Rats. Pulm Med. 2016;2016:7601393.
  27. Goliomytis M, Kartsonas N, Charismiadou MA, Symeon GK, Simitzis PE, Deligeorgis SG. The Influence of Naringin or Hesperidin Dietary Supplementation on Broiler Meat Quality and Oxidative Stability. PLoS ONE. 2015;10(10):e0141652.
  28. Paredes A, Alzuru M, Mendez J, Rodríguez-ortega M. Anti-Sindbis activity of flavanones hesperetin and naringenin. Biol Pharm Bull. 2003;26(1):108-9.
  29. Adebiyi OO, Adebiyi OA, Owira PM. Naringin Reverses Hepatocyte Apoptosis and Oxidative Stress Associated with HIV-1 Nucleotide Reverse Transcriptase Inhibitors-Induced Metabolic Complications. Nutrients. 2015;7(12):10352-68.
  30. Adebiyi OO, Adebiyi OA, Owira P. Naringin improves zidovudine- and stavudine-induced skeletal muscle complications in rats. Hum Exp Toxicol. 2016.
  31. Yin FM, Xiao LB, Zhang Y. [Research progress on Drynaria fortunei naringin on inflammation and bone activity]. Zhongguo Gu Shang. 2015;28(2):182-6.
  32. Kawaguchi K, Maruyama H, Hasunuma R, Kumazawa Y. Suppression of inflammatory responses after onset of collagen-induced arthritis in mice by oral administration of the Citrus flavanone naringin. Immunopharmacol Immunotoxicol. 2011;33(4):723-9.
  33. Ahmad SF, Zoheir KM, Abdel-hamied HE, et al. Amelioration of autoimmune arthritis by naringin through modulation of T regulatory cells and Th1/Th2 cytokines. Cell Immunol. 2014;287(2):112-20.
  34. Lee JH, Kim GH. Evaluation of antioxidant and inhibitory activities for different subclasses flavonoids on enzymes for rheumatoid arthritis. J Food Sci. 2010;75(7):H212-7.
  35. Yin FM, Xiao LB, Zhang Y. [Research progress on Drynaria fortunei naringin on inflammation and bone activity]. Zhongguo Gu Shang. 2015;28(2):182-6.
  36. Xu T, Wang L, Tao Y, Ji Y, Deng F, Wu XH. The Function of Naringin in Inducing Secretion of Osteoprotegerin and Inhibiting Formation of Osteoclasts. Evid Based Complement Alternat Med. 2016;2016:8981650.
  37. Epasinghe DJ, Yiu C, Burrow MF. Effect of flavonoids on remineralization of artificial root caries. Aust Dent J. 2015.
  38. Zhao Y, Li Z, Wang W, et al. Naringin Protects Against Cartilage Destruction in Osteoarthritis Through Repression of NF-κB Signaling Pathway. 2016;39(1):385-92.
  39. Chtourou Y, Gargouri B, Kebieche M, Fetoui H. Naringin Abrogates Cisplatin-Induced Cognitive Deficits and Cholinergic Dysfunction Through the Down-Regulation of AChE Expression and iNOS Signaling Pathways in Hippocampus of Aged Rats. J Mol Neurosci. 2015;56(2):349-62.
  40. Chtourou Y, Aouey B, Kebieche M, Fetoui H. Protective role of naringin against cisplatin induced oxidative stress, inflammatory response and apoptosis in rat striatum via suppressing ROS-mediated NF-κB and P53 signaling pathways. Chem Biol Interact. 2015;239:76-86.
  41. Ramalingayya GV, Nampoothiri M, Nayak PG, et al. Naringin and Rutin Alleviates Episodic Memory Deficits in Two Differentially Challenged Object Recognition Tasks. Pharmacogn Mag. 2016;12(Suppl 1):S63-70.
  42. Wang DM, Yang YJ, Zhang L, Zhang X, Guan FF, Zhang LF. Naringin Enhances CaMKII Activity and Improves Long-Term Memory in a Mouse Model of Alzheimer’s Disease. Int J Mol Sci. 2013;14(3):5576-86.
  43. Wang D, Gao K, Li X, et al. Long-term naringin consumption reverses a glucose uptake defect and improves cognitive deficits in a mouse model of Alzheimer’s disease. Pharmacol Biochem Behav. 2012;102(1):13-20.
  44. Kim HD, Jeong KH, Jung UJ, Kim SR. Naringin treatment induces neuroprotective effects in a mouse model of Parkinson’s disease in vivo, but not enough to restore the lesioned dopaminergic system. J Nutr Biochem. 2016;28:140-6.
  45. Leem E, Nam JH, Jeon MT, et al. Naringin protects the nigrostriatal dopaminergic projection through induction of GDNF in a neurotoxin model of Parkinson’s disease. J Nutr Biochem. 2014;25(7):801-6.
  46. Jung UJ, Kim SR. Effects of naringin, a flavanone glycoside in grapefruits and citrus fruits, on the nigrostriatal dopaminergic projection in the adult brain. Neural Regen Res. 2014;9(16):1514-7.
  47. Sachdeva AK, Kuhad A, Chopra K. Naringin ameliorates memory deficits in experimental paradigm of Alzheimer’s disease by attenuating mitochondrial dysfunction. Pharmacol Biochem Behav. 2014;127:101-10.
  48. Golechha M, Sarangal V, Bhatia J, Chaudhry U, Saluja D, Arya DS. Naringin ameliorates pentylenetetrazol-induced seizures and associated oxidative stress, inflammation, and cognitive impairment in rats: possible mechanisms of neuroprotection. Epilepsy Behav. 2014;41:98-102.
  49. Adebiyi OA, Adebiyi OO, Owira PM. Naringin Reduces Hyperglycemia-Induced Cardiac Fibrosis by Relieving Oxidative Stress. PLoS ONE. 2016;11(3):e0149890.
  50. Dhanya R, Arun KB, Nisha VM, et al. Preconditioning L6 Muscle Cells with Naringin Ameliorates Oxidative Stress and Increases Glucose Uptake. PLoS ONE. 2015;10(7):e0132429.
  51. Wang D, Yan J, Chen J, Wu W, Zhu X, Wang Y. Naringin Improves Neuronal Insulin Signaling, Brain Mitochondrial Function, and Cognitive Function in High-Fat Diet-Induced Obese Mice. Cell Mol Neurobiol. 2015;35(7):1061-71.
  52. Chen F, Zhang N, Ma X, et al. Naringin Alleviates Diabetic Kidney Disease through Inhibiting Oxidative Stress and Inflammatory Reaction. PLoS ONE. 2015;10(11):e0143868.
  53. Sun X, Li F, Ma X, et al. The Effects of Combined Treatment with Naringin and Treadmill Exercise on Osteoporosis in Ovariectomized Rats. Sci Rep. 2015;5:13009.
  54. Anuja GI, Latha PG, Suja SR, et al. Anti-inflammatory and analgesic properties of Drynaria quercifolia (L.) J. Smith. J Ethnopharmacol. 2010;132(2):456-60.
  55. Kandhare AD, Alam J, Patil MV, Sinha A, Bodhankar SL. Wound healing potential of naringin ointment formulation via regulating the expression of inflammatory, apoptotic and growth mediators in experimental rats. Pharm Biol. 2016;54(3):419-32.
  56. Chanet A, Milenkovic D, Deval C, et al. Naringin, the major grapefruit flavonoid, specifically affects atherosclerosis development in diet-induced hypercholesterolemia in mice. J Nutr Biochem. 2012;23(5):469-77.
  57. Etxeberria U, De la garza AL, Martíinez JA, Milagro I. Biocompounds Attenuating the Development of Obesity and Insulin Resistance Produced by a High-fat Sucrose Diet. Nat Prod Commun. 2015;10(8):1417-20.
  58. Nakajima VM, Madeira JV, Macedo GA, Macedo JA. Biotransformation effects on anti lipogenic activity of citrus extracts. Food Chem. 2016;197 Pt B:1046-53.
  59. Stohs SJ, Badmaev V. A Review of Natural Stimulant and Non-stimulant Thermogenic Agents. Phytother Res. 2016;30(5):732-40.
  60. Manna K, Das U, Das D, et al. Naringin inhibits gamma radiation-induced oxidative DNA damage and inflammation, by modulating p53 and NF-κB signaling pathways in murine splenocytes. Free Radic Res. 2015;49(4):422-39.
  61. Ren X, Shi Y, Zhao D, et al. Naringin protects ultraviolet B-induced skin damage by regulating p38 MAPK signal pathway. J Dermatol Sci. 2016;82(2):106-14.
  62. Takekoshi S, Nagata H, Kitatani K. Flavonoids enhance melanogenesis in human melanoma cells. Tokai J Exp Clin Med. 2014;39(3):116-21.
  63. Jiao HY, Su WW, Li PB, et al. Therapeutic effects of naringin in a guinea pig model of ovalbumin-induced cough-variant asthma. Pulm Pharmacol Ther. 2015;33:59-65.
  64. Casey SC, Amedei A, Aquilano K, et al. Cancer prevention and therapy through the modulation of the tumor microenvironment. Semin Cancer Biol. 2015;35 Suppl:S199-223.
  65. Sun Y, Gu J. [Study on effect of naringenin in inhibiting migration and invasion of breast cancer cells and its molecular mechanism]. Zhongguo Zhong Yao Za Zhi. 2015;40(6):1144-50.
  66. Song HM, Park GH, Eo HJ, et al. Anti-Proliferative Effect of Naringenin through p38-Dependent Downregulation of Cyclin D1 in Human Colorectal Cancer Cells. Biomol Ther (Seoul). 2015;23(4):339-44.
  67. Yen HR, Liu CJ, Yeh CC. Naringenin suppresses TPA-induced tumor invasion by suppressing multiple signal transduction pathways in human hepatocellular carcinoma cells. Chem Biol Interact. 2015;235:1-9.
  68. Maggioni D, Nicolini G, Rigolio R, et al. Myricetin and naringenin inhibit human squamous cell carcinoma proliferation and migration in vitro. Nutr Cancer. 2014;66(7):1257-67.
  69. Liao AC, Kuo CC, Huang YC, et al. Naringenin inhibits migration of bladder cancer cells through downregulation of AKT and MMP‑ Mol Med Rep. 2014;10(3):1531-6.
  70. Lou C, Zhang F, Yang M, et al. Naringenin decreases invasiveness and metastasis by inhibiting TGF-β-induced epithelial to mesenchymal transition in pancreatic cancer cells. PLoS ONE. 2012;7(12).
  71. Bao L, Liu F, Guo HB, et al. Naringenin inhibits proliferation, migration, and invasion as well as induces apoptosis of gastric cancer SGC7901 cell line by downregulation of AKT pathway. Tumour Biol. 2016.
  72. Song HM, Park GH, Eo HJ, Jeong JB. Naringenin-Mediated ATF3 Expression Contributes to Apoptosis in Human Colon Cancer. Biomol Ther (Seoul). 2016;24(2):140-6.
  73. Abaza MS, Orabi KY, Al-quattan E, Al-attiyah RJ. Growth inhibitory and chemo-sensitization effects of naringenin, a natural flavanone purified from Thymus vulgaris, on human breast and colorectal cancer. Cancer Cell Int. 2015;15:46.
  74. Ayob Z, Mohd bohari SP, Abd samad A, Jamil S. Cytotoxic Activities against Breast Cancer Cells of Local Justicia gendarussa Crude Extracts. Evid Based Complement Alternat Med. 2014.
  75. Li RF, Feng YQ, Chen JH, Ge LT, Xiao SY, Zuo XL. Naringenin suppresses K562 human leukemia cell proliferation and ameliorates Adriamycin-induced oxidative damage in polymorphonuclear leukocytes. Exp Ther Med. 2015;9(3):697-706.
  76. Ahamad MS, Siddiqui S, Jafri A, Ahmad S, Afzal M, Arshad M. Induction of apoptosis and antiproliferative activity of naringenin in human epidermoid carcinoma cell through ROS generation and cell cycle arrest. PLoS ONE. 2014;9(10):e110003.
  77. Arul D, Subramanian P. Naringenin (citrus flavonone) induces growth inhibition, cell cycle arrest and apoptosis in human hepatocellular carcinoma cells. Pathol Oncol Res. 2013;19(4):763-70.
  78. Ekambaram G, Rajendran P, Magesh V, Sakthisekaran D. Naringenin reduces tumor size and weight lost in N-methyl-N’-nitro-N-nitrosoguanidine-induced gastric carcinogenesis in rats. Nutr Res. 2008;28(2):106-12.
  79. Qin L, Jin L, Lu L, et al. Naringenin reduces lung metastasis in a breast cancer resection model. Protein Cell. 2011;2(6):507-16.
  80. Sabarinathan D, Mahalakshmi P, Vanisree AJ. Naringenin, a flavanone inhibits the proliferation of cerebrally implanted C6 glioma cells in rats. Chem Biol Interact. 2011;189(1-2):26-36.
  81. Bodduluru LN, Kasala ER, Madhana RM, et al. Naringenin ameliorates inflammation and cell proliferation in benzo(a)pyrene induced pulmonary carcinogenesis by modulating CYP1A1, NFκB and PCNA expression. Int Immunopharmacol. 2016;30:102-10.
  82. Sabarinathan D, Mahalakshmi P, Vanisree AJ. Naringenin promote apoptosis in cerebrally implanted C6 glioma cells. Mol Cell Biochem. 2010;345(1-2):215-22.
  83. Shi D, Xu Y, Du X, et al. Co-treatment of THP-1 cells with naringenin and curcumin induces cell cycle arrest and apoptosis via numerous pathways. Mol Med Rep. 2015;12(6):8223-8.
  84. Torricelli P, Ricci P, Provenzano B, Lentini A, Tabolacci C. Synergic effect of α-tocopherol and naringenin in transglutaminase-induced differentiation of human prostate cancer cells. Amino Acids. 2011;41(5):1207-14.
  85. Bulzomi P, Bolli A, Galluzzo P, Acconcia F, Ascenzi P, Marino M. The naringenin-induced proapoptotic effect in breast cancer cell lines holds out against a high bisphenol a background. IUBMB Life. 2012;64(8):690-6.
  86. Kumar SP, Birundha K, Kaveri K, Devi KT. Antioxidant studies of chitosan nanoparticles containing naringenin and their cytotoxicity effects in lung cancer cells. Int J Biol Macromol. 2015;78:87-95.
  87. Fouad AA, Albuali WH, Jresat I. Protective Effect of Naringenin against Lipopolysaccharide-Induced Acute Lung Injury in Rats. Pharmacology. 2016;97(5-6):224-32.
  88. Mostafa Hel-S, Abd el-baset SA, Kattaia AA, Zidan RA, Al sadek MM. Efficacy of naringenin against permethrin-induced testicular toxicity in rats. Int J Exp Pathol. 2016;97(1):37-49.
  89. Chtourou Y, Slima AB, Gdoura R, Fetoui H. Naringenin Mitigates Iron-Induced Anxiety-Like Behavioral Impairment, Mitochondrial Dysfunctions, Ectonucleotidases and Acetylcholinesterase Alteration Activities in Rat Hippocampus. Neurochem Res. 2015;40(8):1563-75.
  90. Sachdeva S, Pant SC, Kushwaha P, Bhargava R, Flora SJ. Sodium tungstate induced neurological alterations in rat brain regions and their response to antioxidants. Food Chem Toxicol. 2015;82:64-71.
  91. Lin JL, Wang YD, Ma Y, et al. Protective effects of naringenin eye drops on N-methyl-N-nitrosourea-induced photoreceptor cell death in rats. Int J Ophthalmol. 2014;7(3):391-6.
  92. Nahmias Y, Goldwasser J, Casali M, et al. Apolipoprotein B-dependent hepatitis C virus secretion is inhibited by the grapefruit flavonoid naringenin. Hepatology. 2008;47(5):1437-45.
  93. Paredes A, Alzuru M, Mendez J, Rodríguez-ortega M. Anti-Sindbis activity of flavanones hesperetin and naringenin. Biol Pharm Bull. 2003;26(1):108-9.
  94. Pinho-ribeiro FA, Zarpelon AC, Fattori V, et al. Naringenin reduces inflammatory pain in mice. 2016;105:508-519.
  95. Manchope MF, Calixto-campos C, Coelho-silva L, et al. Naringenin Inhibits Superoxide Anion-Induced Inflammatory Pain: Role of Oxidative Stress, Cytokines, Nrf-2 and the NO-cGMP-PKG-KATPChannel Signaling Pathway. PLoS ONE. 2016;11(4).
  96. Oršolić N, Goluža E, Dikić D, et al. Role of flavonoids on oxidative stress and mineral contents in the retinoic acid-induced bone loss model of rat. Eur J Nutr. 2014;53(5):1217-27.
  97. La VD, Tanabe S, Grenier D. Naringenin inhibits human osteoclastogenesis and osteoclastic bone resorption. J Periodont Res. 2009;44(2):193-8.
  98. Ming LG, Lv X, Ma XN, et al. The prenyl group contributes to activities of phytoestrogen 8-prenynaringenin in enhancing bone formation and inhibiting bone resorption in vitro. Endocrinology. 2013;154(3):1202-14.
  99. Ming LG, Ge BF, Wang MG, Chen KM. Comparison between 8-prenylnarigenin and narigenin concerning their activities on promotion of rat bone marrow stromal cells’ osteogenic differentiation in vitro. Cell Prolif. 2012;45(6):508-15.
  100. Amat-ur-rasool H, Ahmed M. Designing Second Generation Anti-Alzheimer Compounds as Inhibitors of Human Acetylcholinesterase: Computational Screening of Synthetic Molecules and Dietary Phytochemicals. PLoS ONE. 2015;10(9).
  101. Ghofrani S, Joghataei MT, Mohseni S, et al. Naringenin improves learning and memory in an Alzheimer’s disease rat model: Insights into the underlying mechanisms. Eur J Pharmacol. 2015;764:195-201.
  102. Chtourou Y, Fetoui H, Gdoura R. Protective effects of naringenin on iron-overload-induced cerebral cortex neurotoxicity correlated with oxidative stress. Biol Trace Elem Res. 2014;158(3):376-83.
  103. Zbarsky V, Datla KP, Parkar S, Rai DK, Aruoma OI, Dexter DT. Neuroprotective properties of the natural phenolic antioxidants curcumin and naringenin but not quercetin and fisetin in a 6-OHDA model of Parkinson’s disease. Free Radic Res. 2005;39(10):1119-25.
  104. Lim W, Song G. Naringenin-induced migration of embrynoic trophectoderm cells is mediated via PI3K/AKT and ERK1/2 MAPK signaling cascades. Mol Cell Endocrinol. 2016;428:28-37.
  105. Yi LT, Li CF, Zhan X, et al. Involvement of monoaminergic system in the antidepressant-like effect of the flavonoid naringenin in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34(7):1223-8.
  106. Yi LT, Liu BB, Li J, et al. BDNF signaling is necessary for the antidepressant-like effect of naringenin. Prog Neuropsychopharmacol Biol Psychiatry. 2014;48:135-41.
  107. Yi LT, Li J, Li HC, et al. Antidepressant-like behavioral, neurochemical and neuroendocrine effects of naringenin in the mouse repeated tail suspension test. Prog Neuropsychopharmacol Biol Psychiatry. 2012;39(1):175-81.
  108. Ozkaya A, Sahin Z, Dag U, Ozkaraca M. Effects of Naringenin on Oxidative Stress and Histopathological Changes in the Liver of Lead Acetate Administered Rats. J Biochem Mol Toxicol. 2016;30(5):243-8.
  109. Roy S, Ahmed F, Banerjee S, Saha U. Naringenin ameliorates streptozotocin-induced diabetic rat renal impairment by downregulation of TGF-β1 and IL-1 via modulation of oxidative stress correlates with decreased apoptotic events. Pharm Biol. 2016;:1-12.
  110. Ren B, Qin W, Wu F, et al. Apigenin and naringenin regulate glucose and lipid metabolism, and ameliorate vascular dysfunction in type 2 diabetic rats. Eur J Pharmacol. 2016;773:13-23.
  111. Bhattacharya S, Oksbjerg N, Young JF, Jeppesen PB. Caffeic acid, naringenin and quercetin enhance glucose-stimulated insulin secretion and glucose sensitivity in INS-1E cells. Diabetes Obes Metab. 2014;16(7):602-12.
  112. Habauzit V, Verny MA, Milenkovic D, et al. Flavanones protect from arterial stiffness in postmenopausal women consuming grapefruit juice for 6 mo: a randomized, controlled, crossover trial. Am J Clin Nutr. 2015;102(1):66-74.
  113. Orhan IE, Nabavi SF, Daglia M, Tenore GC, Mansouri K, Nabavi SM. Naringenin and atherosclerosis: a review of literature. Curr Pharm Biotechnol. 2015;16(3):245-51.
  114. Zhang N, Yang Z, Yuan Y, et al. Naringenin attenuates pressure overload-induced cardiac hypertrophy. Exp Ther Med. 2015;10(6):2206-2212.
  115. Li YR, Chen DY, Chu CL, et al. Naringenin inhibits dendritic cell maturation and has therapeutic effects in a murine model of collagen-induced arthritis. J Nutr Biochem. 2015;26(12):1467-78.
  116. Du G, Jin L, Han X, Song Z, Zhang H, Liang W. Naringenin: a potential immunomodulator for inhibiting lung fibrosis and metastasis. Cancer Res. 2009;69(7):3205-12.
  117. Qin L, Jin L, Lu L, et al. Naringenin reduces lung metastasis in a breast cancer resection model. Protein Cell. 2011;2(6):507-16.
  118. Nasr-bouzaiene N, Sassi A, Bedoui A, Krifa M, Chekir-ghedira L, Ghedira K. Immunomodulatory and cellular antioxidant activities of pure compounds from Teucrium ramosissimum Desf. Tumour Biol. 2015.
  119. Kim JH, Lee JK. Naringenin enhances NK cell lysis activity by increasing the expression of NKG2D ligands on Burkitt’s lymphoma cells. Arch Pharm Res. 2015;38(11):2042-8.
  120. Farzaei MH, Rahimi R, Abdollahi M. The role of dietary polyphenols in the management of inflammatory bowel disease. Curr Pharm Biotechnol. 2015;16(3):196-210.
  121. Al-rejaie SS, Abuohashish HM, Al-enazi MM, Al-assaf AH, Parmar MY, Ahmed MM. Protective effect of naringenin on acetic acid-induced ulcerative colitis in rats. World J Gastroenterol. 2013;19(34):5633-44.
  122. Azuma T, Shigeshiro M, Kodama M, Tanabe S, Suzuki T. Supplemental naringenin prevents intestinal barrier defects and inflammation in colitic mice. J Nutr. 2013;143(6):827-34.
  123. Chattopadhyay D, Sen S, Chatterjee R, Roy D, James J, Thirumurugan K. Context- and dose-dependent modulatory effects of naringenin on survival and development of Drosophila melanogaster. Biogerontology. 2016;17(2):383-93.
  124. Assini JM, Mulvihill EE, Burke AC, et al. Naringenin prevents obesity, hepatic steatosis, and glucose intolerance in male mice independent of fibroblast growth factor 21. Endocrinology. 2015;156(6):2087-102.
  125. Ke JY, Cole RM, Hamad EM, et al. Citrus flavonoid, naringenin, increases locomotor activity and reduces diacylglycerol accumulation in skeletal muscle of obese ovariectomized mice. Mol Nutr Food Res. 2016;60(2):313-24.!
  126. Kumar S, Tiku AB. Biochemical and Molecular Mechanisms of Radioprotective Effects of Naringenin, a Phytochemical from Citrus Fruits. J Agric Food Chem. 2016;64(8):1676-85.
  127. Jung SK, Ha SJ, Jung CH, et al. Naringenin targets ERK2 and suppresses UVB-induced photoaging. J Cell Mol Med. 2016;20(5):909-19.
  128. Martinez RM, Pinho-ribeiro FA, Steffen VS, et al. Topical Formulation Containing Naringenin: Efficacy against Ultraviolet B Irradiation-Induced Skin Inflammation and Oxidative Stress in Mice. PLoS ONE. 2016;11(1):e0146296.
  129. Martinez RM, Pinho-ribeiro FA, Steffen VS, et al. Naringenin Inhibits UVB Irradiation-Induced Inflammation and Oxidative Stress in the Skin of Hairless Mice. J Nat Prod. 2015;78(7):1647-55.
  130. Kawakami CM, Gaspar LR. Mangiferin and naringenin affect the photostability and phototoxicity of sunscreens containing avobenzone. J Photochem Photobiol B, Biol. 2015;151:239-47.
  131. Nasr bouzaiene N, Chaabane F, Sassi A, Chekir-ghedira L, Ghedira K. Effect of apigenin-7-glucoside, genkwanin and naringenin on tyrosinase activity and melanin synthesis in B16F10 melanoma cells. Life Sci. 2016;144:80-5.
  132. Liu Y, Wang P, Chen F, et al. Role of plant polyphenols in acrylamide formation and elimination. Food Chem. 2015;186:46-53.
  133. Keiler AM, Dörfelt P, Chatterjee N, et al. Assessment of the effects of naringenin-type flavanones in uterus and vagina. J Steroid Biochem Mol Biol. 2015;145:49-57.
  134. Lee CJ, Wilson L, Jordan MA, Nguyen V, Tang J, Smiyun G. Hesperidin suppressed proliferations of both human breast cancer and androgen-dependent prostate cancer cells. Phytother Res. 2010;24 Suppl 1:S15-9.
  135. Choi EJ. Hesperetin induced G1-phase cell cycle arrest in human breast cancer MCF-7 cells: involvement of CDK4 and p21. Nutr Cancer. 2007;59(1):115-9.
  136. Bracke M, Vyncke B, Opdenakker G, Foidart JM, De pestel G, Mareel M. Effect of catechins and citrus flavonoids on invasion in vitro. Clin Exp Metastasis. 1991;9(1):13-25.
  137. Banjerdpongchai R, Wudtiwai B, Khaw-on P, Rachakhom W, Duangnil N, Kongtawelert P. Hesperidin from Citrus seed induces human hepatocellular carcinoma HepG2 cell apoptosis via both mitochondrial and death receptor pathways. Tumour Biol. 2016;37(1):227-37.
  138. Nazari M, Ghorbani A, Hekmat-doost A, Jeddi-tehrani M, Zand H. Inactivation of nuclear factor-κB by citrus flavanone hesperidin contributes to apoptosis and chemo-sensitizing effect in Ramos cells. Eur J Pharmacol. 2011;650(2-3):526-33.
  139. Park HJ, Kim MJ, Ha E, Chung JH. Apoptotic effect of hesperidin through caspase3 activation in human colon cancer cells, SNU-C4. Phytomedicine. 2008;15(1-2):147-51.
  140. Ghorbani A, Nazari M, Jeddi-tehrani M, Zand H. The citrus flavonoid hesperidin induces p53 and inhibits NF-κB activation in order to trigger apoptosis in NALM-6 cells: involvement of PPARγ-dependent mechanism. Eur J Nutr. 2012;51(1):39-46.
  141. Adan A, Baran Y. The pleiotropic effects of fisetin and hesperetin on human acute promyelocytic leukemia cells are mediated through apoptosis, cell cycle arrest, and alterations in signaling networks. Tumour Biol. 2015;36(11):8973-84.
  142. Yumnam S, Hong GE, Raha S, et al. Mitochondrial Dysfunction and Ca(2+) Overload Contributes to Hesperidin Induced Paraptosis in Hepatoblastoma Cells, HepG2. J Cell Physiol. 2016;231(6):1261-8.
  143. Birsu cincin Z, Unlu M, Kiran B, Sinem bireller E, Baran Y, Cakmakoglu B. Anti-proliferative, apoptotic and signal transduction effects of hesperidin in non-small cell lung cancer cells. Cell Oncol (Dordr). 2015;38(3):195-204.
  144. Palit S, Kar S, Sharma G, Das PK. Hesperetin Induces Apoptosis in Breast Carcinoma by Triggering Accumulation of ROS and Activation of ASK1/JNK Pathway. J Cell Physiol. 2015;230(8):1729-39.
  145. Tanaka T, Makita H, Kawabata K, et al. Chemoprevention of azoxymethane-induced rat colon carcinogenesis by the naturally occurring flavonoids, diosmin and hesperidin. Carcinogenesis. 1997;18(5):957-65.
  146. Kamaraj S, Anandakumar P, Jagan S, Ramakrishnan G, Devaki T. Modulatory effect of hesperidin on benzo(a)pyrene induced experimental lung carcinogenesis with reference to COX-2, MMP-2 and MMP-9. Eur J Pharmacol. 2010;649(1-3):320-7.
  147. Yang M, Tanaka T, Hirose Y, Deguchi T, Mori H, Kawada Y. Chemopreventive effects of diosmin and hesperidin on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary-bladder carcinogenesis in male ICR mice. Int J Cancer. 1997;73(5):719-24.;2-0/abstract
  148. Tanaka T, Makita H, Ohnishi M, et al. Chemoprevention of 4-nitroquinoline 1-oxide-induced oral carcinogenesis by dietary curcumin and hesperidin: comparison with the protective effect of beta-carotene. Cancer Res. 1994;54(17):4653-9.
  149. Tanaka T, Makita H, Ohnishi M, et al. Chemoprevention of 4-nitroquinoline 1-oxide-induced oral carcinogenesis in rats by flavonoids diosmin and hesperidin, each alone and in combination. Cancer Res. 1997;57(2):246-52.
  150. Tanaka T, Makita H, Kawabata K, et al. Modulation of N-methyl-N-amylnitrosamine-induced rat oesophageal tumourigenesis by dietary feeding of diosmin and hesperidin, both alone and in combination. Carcinogenesis. 1997;18(4):761-9.
  151. Zhang J, Wu D, Vikash, et al. Hesperetin Induces the Apoptosis of Gastric Cancer Cells via Activating Mitochondrial Pathway by Increasing Reactive Oxygen Species. Dig Dis Sci. 2015;60(10):2985-95.
  152. Saiprasad G, Chitra P, Manikandan R, Sudhandiran G. Hesperidin induces apoptosis and triggers autophagic markers through inhibition of Aurora-A mediated phosphoinositide-3-kinase/Akt/mammalian target of rapamycin and glycogen synthase kinase-3 beta signalling cascades in experimental colon carcinogenesis. Eur J Cancer. 2014;50(14):2489-507.
  153. Gwiazdowska D, Juś K, Jasnowska-małecka J, Kluczyńska K. The impact of polyphenols on Bifidobacterium growth. Acta Biochim Pol. 2015;62(4):895-901.
  154. Abuelsaad AS, Allam G, Al-solumani AA. Hesperidin inhibits inflammatory response induced by Aeromonas hydrophila infection and alters CD4+/CD8+ T cell ratio. Mediators Inflamm. 2014;2014:393217.
  155. Siddiqi A, Nafees S, Rashid S, Sultana S, Saidullah B. Hesperidin ameliorates trichloroethylene-induced nephrotoxicity by abrogation of oxidative stress and apoptosis in wistar rats. Mol Cell Biochem. 2015;406(1-2):9-20.
  156. Anandan R, Subramanian P. Renal protective effect of hesperidin on gentamicin-induced acute nephrotoxicity in male Wistar albino rats. Redox Rep. 2012;17(5):219-26.
  157. Sahu BD, Kuncha M, Sindhura GJ, Sistla R. Hesperidin attenuates cisplatin-induced acute renal injury by decreasing oxidative stress, inflammation and DNA Phytomedicine. 2013;20(5):453-60.
  158. Kamel KM, Abd el-raouf OM, Metwally SA, Abd el-latif HA, El-sayed ME. Hesperidin and rutin, antioxidant citrus flavonoids, attenuate cisplatin-induced nephrotoxicity in rats. J Biochem Mol Toxicol. 2014;28(7):312-9.
  159. Polat N, Ciftci O, Cetin A, Yılmaz T. Toxic effects of systemic cisplatin on rat eyes and the protective effect of hesperidin against this toxicity. Cutan Ocul Toxicol. 2016;35(1):1-7.
  160. Kaya K, Ciftci O, Cetin A, Doğan H, Başak N. Hesperidin protects testicular and spermatological damages induced by cisplatin in rats. 2015;47(7):793-800.
  161. Omar HA, Mohamed WR, Arafa el-SA, et al. Hesperidin alleviates cisplatin-induced hepatotoxicity in rats without inhibiting its antitumor activity. Pharmacol Rep. 2016;68(2):349-56.
  162. Saha RK, Takahashi T, Suzuki T. Glucosyl hesperidin prevents influenza a virus replication in vitro by inhibition of viral sialidase. Biol Pharm Bull. 2009;32(7):1188-92.
  163. Carvalho OV, Botelho CV, Ferreira CG, et al. In vitro inhibition of canine distemper virus by flavonoids and phenolic acids: implications of structural differences for antiviral design. Res Vet Sci. 2013;95(2):717-24.
  164. Bae EA, Han MJ, Lee M, Kim DH. In vitro inhibitory effect of some flavonoids on rotavirus infectivity. Biol Pharm Bull. 2000;23(9):1122-4.
  165. Panasiak W, Wleklik M, Oraczewska A, Luczak M. Influence of flavonoids on combined experimental infections with EMC virus and Staphylococcus aureus in mice. Acta Microbiol Pol. 1989;38(2):185-8.
  166. Ahmed YM, Messiha BA, Abo-saif AA. Protective Effects of Simvastatin and Hesperidin against Complete Freund’s Adjuvant-Induced Rheumatoid Arthritis in Rats. Pharmacology. 2015;96(5-6):217-25.
  167. Li R, Cai L, Xie XF, Yang F, Li J. Hesperidin suppresses adjuvant arthritis in rats by inhibiting synoviocyte activity. Phytother Res. 2010;24 Suppl 1:S71-6.
  168. Martin BR, Mccabe GP, Mccabe L, et al. Effect of Hesperidin With and Without a Calcium (Calcilock) Supplement on Bone Health in Postmenopausal Women. J Clin Endocrinol Metab. 2016;101(3):923-7.
  169. Chiba H, Kim H, Matsumoto A, et al. Hesperidin prevents androgen deficiency-induced bone loss in male mice. Phytother Res. 2014;28(2):289-95.
  170. Habauzit V, Sacco SM, Gil-izquierdo A, et al. Differential effects of two citrus flavanones on bone quality in senescent male rats in relation to their bioavailability and metabolism. Bone. 2011;49(5):1108-16.
  171. Tamilselvam K, Braidy N, Manivasagam T, et al. Neuroprotective effects of hesperidin, a plant flavanone, on rotenone-induced oxidative stress and apoptosis in a cellular model for Parkinson’s disease. Oxid Med Cell Longev. 2013;2013:102741.
  172. Khan MH, Parvez S. Hesperidin ameliorates heavy metal induced toxicity mediated by oxidative stress in brain of Wistar rats. J Trace Elem Med Biol. 2015;31:53-60.
  173. Wang D, Liu L, Zhu X, Wu W, Wang Y. Hesperidin alleviates cognitive impairment, mitochondrial dysfunction and oxidative stress in a mouse model of Alzheimer’s disease. Cell Mol Neurobiol. 2014;34(8):1209-21.
  174. Antunes MS, Goes AT, Boeira SP, Prigol M, Jesse CR. Protective effect of hesperidin in a model of Parkinson’s disease induced by 6-hydroxydopamine in aged mice. Nutrition. 2014;30(11-12):1415-22.
  175. El-marasy SA, Abdallah HM, El-shenawy SM, El-khatib AS, El-shabrawy OA, Kenawy SA. Anti-depressant effect of hesperidin in diabetic rats. Can J Physiol Pharmacol. 2014;92(11):945-52.
  176. Donato F, De gomes MG, Goes AT, et al. Hesperidin exerts antidepressant-like effects in acute and chronic treatments in mice: possible role of l-arginine-NO-cGMP pathway and BDNF levels. Brain Res Bull. 2014;104:19-26.
  177. Cai L, Li R, Wu QQ, Wu TN. [Effect of hesperidin on behavior and HPA axis of rat model of chronic stress-induced depression]. Zhongguo Zhong Yao Za Zhi. 2013;38(2):229-33.
  178. Sharma M, Akhtar N, Sambhav K, Shete G, Bansal AK, Sharma SS. Emerging potential of citrus flavanones as an antioxidant in diabetes and its complications. Curr Top Med Chem. 2015;15(2):187-95.
  179. De oliveira DM, Dourado GK, Cesar TB. Hesperidin associated with continuous and interval swimming improved biochemical and oxidative biomarkers in rats. J Int Soc Sports Nutr. 2013;10:27.
  180. Dimpfel W. Different anticonvulsive effects of hesperidin and its aglycone hesperetin on electrical activity in the rat hippocampus in-vitro. J Pharm Pharmacol. 2006;58(3):375-9.
  181. Zanotti simoes dourado GK, De abreu ribeiro LC, Zeppone carlos I, Borges césar T. Orange juice and hesperidin promote differential innate immune response in macrophages ex vivo. Int J Vitam Nutr Res. 2013;83(3):162-7.
  182. Kamboh AA, Hang SQ, Khan MA, Zhu WY. In vivo immunomodulatory effects of plant flavonoids in lipopolysaccharide-challenged broilers. Animal. 2016;:1-7.
  183. Amiot MJ, Riva C, Vinet A. Effects of dietary polyphenols on metabolic syndrome features in humans: a systematic review. Obes Rev. 2016.
  184. Assini JM, Mulvihill EE, Huff MW. Citrus flavonoids and lipid metabolism. Curr Opin Lipidol. 2013;24(1):34-40.
  185. Pradeep K, Ko KC, Choi MH, Kang JA, Chung YJ, Park SH. Protective effect of hesperidin, a citrus flavanoglycone, against γ-radiation-induced tissue damage in Sprague-Dawley rats. J Med Food. 2012;15(5):419-27.
  186. Martinez RM, Pinho-ribeiro FA, Steffen VS, et al. Topical formulation containing hesperidin methyl chalcone inhibits skin oxidative stress and inflammation induced by ultraviolet B irradiation. Photochem Photobiol Sci. 2016;15(4):554-63.
  187. Madduma hewage SR, Piao MJ, Kang KA, et al. Hesperidin Attenuates Ultraviolet B-Induced Apoptosis by Mitigating Oxidative Stress in Human Keratinocytes. Biomol Ther (Seoul). 2016;24(3):312-9.
  188. Said UZ, Saada HN, Abd-alla MS, Elsayed ME, Amin AM. Hesperidin attenuates brain biochemical changes of irradiated rats. Int J Radiat Biol. 2012;88(8):613-8.
  189. Lee YR, Jung JH, Kim HS. Hesperidin partially restores impaired immune and nutritional function in irradiated mice. J Med Food. 2011;14(5):475-82.
  190. Giannini I, Amato A, Basso L, et al. Flavonoids mixture (diosmin, troxerutin, hesperidin) in the treatment of acute hemorrhoidal disease: a prospective, randomized, triple-blind, controlled trial. Tech Coloproctol. 2015;19(6):339-45.
  191. Man G, Mauro TM, Zhai Y, et al. Topical hesperidin enhances epidermal function in an aged murine model. J Invest Dermatol. 2015;135(4):1184-7.
  192. Usach I, Taléns-visconti R, Magraner-pardo L, Peris JE. Hesperetin induces melanin production in adult human epidermal melanocytes. Food Chem Toxicol. 2015;80:80-4.
  193. Kurata Y, Fukushima S, Hagiwara A, Ito H, Ogawa K, Ito N. Carcinogenicity study of methyl hesperidin in B6C3F1 mice. Food Chem Toxicol. 1990;28(9):613-8.
  194. Carpenter KJ. The discovery of vitamin C. Ann Nutr Metab. 2012;61(3):259-64.
  195. Padayatty SJ, Levine M. Vitamin C: the known, the unknown, and Goldilocks. Oral Dis. 2016;
  196. Shaw JH, Phillips PH, Elvehjem CA. Acute and chronic ascorbic acid deficiencies in the rhesus monkey. Nutr. 1945; vol 29. No. 6:365-372.
  197. Mastrangelo D, Massai L, Lo coco F, et al. Cytotoxic effects of high concentrations of sodium ascorbate on human myeloid cell lines. Ann Hematol. 2015;94(11):1807-16.
  198. Sertkaya A, Wong HH, Jessup A, Beleche T. Key cost drivers of pharmaceutical clinical trials in the United States. Sage Journals. 2016; vol 13, issue 2.
  199. PDQ Cancer Information Summaries – High-dose Vitamin C. 2015. [Available] [May 11, 2016].
  200. Venturelli S, Sinnberg TW, Niessner H, Busch C. Molecular mechanisms of pharmacological doses of ascorbate on cancer cells. Wien Med Wochenschr. 2015;165(11-12):251-7.
  201. Cameron E. Vitamin C and cancer: an overview. Int J Vitam Nutr Res Suppl. 1982;23:115-27.
  202. Malavolti M, Malagoli C, Fiorentini C, et al. Association between dietary vitamin C and risk of cutaneous melanoma in a population of Northern Italy. Int J Vitam Nutr Res. 2013;83(5):291-8.
  203. Vance TM, Wang Y, Su LJ, et al. Dietary Total Antioxidant Capacity is Inversely Associated with Prostate Cancer Aggressiveness in a Population-Based Study. Nutr Cancer. 2016;68(2):214-24.
  204. Kong P, Cai Q, Geng Q, et al. Vitamin intake reduce the risk of gastric cancer: meta-analysis and systematic review of randomized and observational studies. PLoS ONE. 2014;9(12):e116060.
  205. Benade L, Howard T, Burk D. Synergistic killing of Ehrlich ascites carcinoma cells by ascorbate and 3-amino-1,2,4,-triazole. Oncology. 1969;23(1):33-43.
  206. Pires AS, Marques CR, Encarnação JC, et al. Ascorbic acid and colon cancer: an oxidative stimulus to cell death depending on cell profile. Eur J Cell Biol. 2016;
  207. Uetaki M, Tabata S, Nakasuka F, Soga T, Tomita M. Metabolomic alterations in human cancer cells by vitamin C-induced oxidative stress. Sci Rep. 2015;5:13896.
  208. Serrano OK, Parrow NL, Violet PC, et al. Antitumor effect of pharmacologic ascorbate in the B16 murine melanoma model. Free Radic Biol Med. 2015;87:193-203.
  209. Mastrangelo D, Massai L, Lo coco F, et al. Cytotoxic effects of high concentrations of sodium ascorbate on human myeloid cell lines. Ann Hematol. 2015;94(11):1807-16.
  210. Chen N, Yin S, Song X, Fan L, Hu H. Vitamin B₂ Sensitizes Cancer Cells to Vitamin-C-Induced Cell Death via Modulation of Akt and Bad Phosphorylation. J Agric Food Chem. 2015;63(30):6739-48.
  211. Campbell EJ, Vissers MC, Bozonet S, Dyer A, Robinson BA, Dachs GU. Restoring physiological levels of ascorbate slows tumor growth and moderates HIF-1 pathway activity in Gulo(-/-) mice. Cancer Med. 2015;4(2):303-14.
  212. Chen Q, Espey MG, Sun AY, et al. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc Natl Acad Sci USA. 2008;105(32):11105-9.
  213. Takemura Y, Satoh M, Satoh K, Hamada H, Sekido Y, Kubota S. High dose of ascorbic acid induces cell death in mesothelioma cells. Biochem Biophys Res Commun. 2010;394(2):249-53.
  214. Yun J, Mullarky E, Lu C, et al. Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science. 2015;350(6266):1391-6.
  215. Yeom CH, Lee G, Park JH, et al. High dose concentration administration of ascorbic acid inhibits tumor growth in BALB/C mice implanted with sarcoma 180 cancer cells via the restriction of angiogenesis. J Transl Med. 2009;7:70.
  216. Casciari JJ, Riordan HD, Miranda-massari JR, Gonzalez MJ. Effects of high dose ascorbate administration on L-10 tumor growth in guinea pigs. P R Health Sci J. 2005;24(2):145-50.
  217. Roomi MW, Cha J, Kalinovsky T, Roomi N, Niedzwiecki A, Rath M. Effect of a nutrient mixture on the localization of extracellular matrix proteins in HeLa human cervical cancer xenografts in female nude mice. Exp Ther Med. 2015;10(3):901-906.
  218. Ambattu LA, Rekha MR. Collagen synthesis promoting pullulan-PEI-ascorbic acid conjugate as an efficient anti-cancer gene delivery vector. Carbohydr Polym. 2015;126:52-61.
  219. Güney G, Kutlu HM, Genç L. Preparation and characterization of ascorbic acid loaded solid lipid nanoparticles and investigation of their apoptotic effects. Colloids Surf B Biointerfaces. 2014;121:270-80.
  220. Gustafson CB, Yang C, Dickson KM, et al. Epigenetic reprogramming of melanoma cells by vitamin C treatment. Clin Epigenetics. 2015;7(1):51.
  221. Robinson AB, Hunsberger A, Westall FC. Suppression of squamous cell carcinoma in hairless mice by dietary nutrient variation. Mech Ageing Dev. 1994;76(2-3):201-14.
  222. Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer. Proc Natl Acad Sci USA. 1976;73(10):3685-9.
  223. Raymond YC, Glenda CS, Meng LK. Effects of High Doses of Vitamin C on Cancer Patients in Singapore: Nine Cases. Integr Cancer Ther. 2015;
  224. Vollbracht C, Schneider B, Leendert V, Weiss G, Auerbach L, Beuth J. Intravenous vitamin C administration improves quality of life in breast cancer patients during chemo-/radiotherapy and aftercare: results of a retrospective, multicentre, epidemiological cohort study in Germany. In Vivo. 2011;25(6):983-90.
  225. Yeom CH, Jung GC, Song KJ. Changes of terminal cancer patients’ health-related quality of life after high dose vitamin C administration. J Korean Med Sci. 2007;22(1):7-11.
  226. Mikirova N, Casciari J, Rogers A, Taylor P. Effect of high-dose intravenous vitamin C on inflammation in cancer patients. J Transl Med. 2012;10:189.
  227. Mateen S, Moin S, Khan AQ, Zafar A, Fatima N. Increased Reactive Oxygen Species Formation and Oxidative Stress in Rheumatoid Arthritis. PLoS ONE. 2016;11(4):e0152925.
  228. Mohamed R, Shivaprasad HV, Jameel NM, Shekar MA, Vishwanath BS. Neutralization of local toxicity induced by vipera russelli phospholipase A2 by lipophilic derivative of ascorbic acid. Curr Top Med Chem. 2011;11(20):2531-9.
  229. Laing MD. A cure for mushroom poisoning. S Afr Med J. 1984;65(15):590.
  230. Pavlovic V, Cekic S, Kamenov B, Ciric M, Krtinic D. The Effect of Ascorbic Acid on Mancozeb-Induced Toxicity in Rat Thymocytes. Folia Biol (Praha). 2015;61(3):116-23.
  231. Ozmen O. Endosulfan splenic pathology and amelioration by vitamin C in New Zealand rabbit. J Immunotoxicol. 2015;:1-6.
  232. Guo W, Huen K, Park JS, et al. Vitamin C intervention may lower the levels of persistent organic pollutants in blood of healthy women – A pilot study. Food Chem Toxicol. 2016;92:197-204.
  233. Roderique JD, Josef CS, Newcomb AH, Reynolds PS, Somera LG, Spiess BD. Preclinical evaluation of injectable reduced hydroxocobalamin as an antidote to acute carbon monoxide poisoning. J Trauma Acute Care Surg. 2015;79(4 Suppl 2):S116-20.
  234. Abe S, Tanaka Y, Fujise N, et al. An antioxidative nutrient-rich enteral diet attenuates lethal activity and oxidative stress induced by lipopolysaccharide in mice. JPEN J Parenter Enteral Nutr. 2007;31(3):181-7.
  235. Berger MM, Oudemans-van straaten HM. Vitamin C supplementation in the critically ill patient. Curr Opin Clin Nutr Metab Care. 2015;18(2):193-201.
  236. Arslan M, Sezen SC, Turgut HC, et al. Vitamin C ameliorates high dose Dexmedetomidine induced liver injury. Bratisl Lek Listy. 2016;117(1):36-40.
  237. Farombi EO, Onyema OO. Monosodium glutamate-induced oxidative damage and genotoxicity in the rat: modulatory role of vitamin C, vitamin E and quercetin. Hum Exp Toxicol. 2006;25(5):251-9.
  238. Mozhdeganloo Z, Jafari AM, Koohi MK, Heidarpour M. Methylmercury-induced oxidative stress in rainbow trout (Oncorhynchus mykiss) liver: ameliorating effect of vitamin C. Biol Trace Elem Res. 2015;165(1):103-9.
  239. Gulec M, Gurel A, Armutcu F. Vitamin E protects against oxidative damage caused by formaldehyde in the liver and plasma of rats. Mol Cell Biochem. 2006;290(1-2):61-7.
  240. Rezvanjoo B, Rashidi S, Jouyban A, Beheshtiha SH, Samini M. Effects of vitamin C and melatonin on cysteamine-induced duodenal ulcer in a cholestatic rat model: A controlled experimental study. Curr Ther Res Clin Exp. 2010;71(5):322-30.
  241. Kim SR, Ha YM, Kim YM, et al. Ascorbic acid reduces HMGB1 secretion in lipopolysaccharide-activated RAW 264.7 cells and improves survival rate in septic mice by activation of Nrf2/HO-1 signals. Biochem Pharmacol. 2015;95(4):279-89.
  242. Tokuda Y, Miura N, Kobayashi M, et al. Ascorbic acid deficiency increases endotoxin influx to portal blood and liver inflammatory gene expressions in ODS rats. 2015;31(2):373-9.
  243. Fisher BJ, Kraskauskas D, Martin EJ, et al. Attenuation of sepsis-induced organ injury in mice by vitamin C. JPEN J Parenter Enteral Nutr. 2014;38(7):825-39.
  244. Abhilash PA, Harikrishnan R, Indira M. Ascorbic acid suppresses endotoxemia and NF-κB signaling cascade in alcoholic liver fibrosis in guinea pigs: a mechanistic approach. Toxicol Appl Pharmacol. 2014;274(2):215-24.
  245. Lowes DA, Webster NR, Galley HF. Dehydroascorbic acid as pre-conditioner: protection from lipopolysaccharide induced mitochondrial damage. Free Radic Res. 2010;44(3):283-92.
  246. Fisher BJ, Seropian IM, Kraskauskas D, et al. Ascorbic acid attenuates lipopolysaccharide-induced acute lung injury. Crit Care Med. 2011;39(6):1454-60.
  247. Mckinnon RL, Lidington D, Tyml K. Ascorbate inhibits reduced arteriolar conducted vasoconstriction in septic mouse cremaster muscle. Microcirculation. 2007;14(7):697-707.
  248. Kanter M, Coskun O, Armutcu F, Uz YH, Kizilay G. Protective effects of vitamin C, alone or in combination with vitamin A, on endotoxin-induced oxidative renal tissue damage in rats. Tohoku J Exp Med. 2005;206(2):155-62.
  249. Chen MF, Yang CM, Su CM, Hu ML. Vitamin C protects against cisplatin-induced nephrotoxicity and damage without reducing its effectiveness in C57BL/6 mice xenografted with Lewis lung carcinoma. Nutr Cancer. 2014;66(7):1085-91.
  250. Al-asmari AK, Khan AQ, Al-masri N. Mitigation of 5-fluorouracil-induced liver damage in rats by vitamin C via targeting redox-sensitive transcription factors. Hum Exp Toxicol. 2016;
  251. Peng LJ, Lu DX, Qi RB, Zhang T, Wang Z, Sun Y. [Therapeutic effect of intravenous high-dose vitamin C on implanted hepatoma in rats]. Nan Fang Yi Ke Da Xue Xue Bao. 2009;29(2):264-6.
  252. Cheng LL, Liu YY, Li B, Li SY, Ran PX. [An in vitro study on the pharmacological ascorbate treatment of influenza virus]. Zhonghua Jie He He Hu Xi Za Zhi. 2012;35(7):520-3.
  253. Wintergerst ES, Maggini S, Hornig DH. Immune-enhancing role of vitamin C and zinc and effect on clinical conditions. Ann Nutr Metab. 2006;50(2):85-94.
  254. Harakeh S, Jariwalla RJ. Comparative study of the anti-HIV activities of ascorbate and thiol-containing reducing agents in chronically HIV-infected cells. Am J Clin Nutr. 1991;54(6 Suppl):1231S-1235S.
  255. Dalton WL. Massive Doses of Vitamin C in the Treatment of Viral Diseases. Journal of the Indiana State Medical Association. 1962.
  256. Riordan Clinic. High-dose Intravenous Vitamin C as a Successful Treatment of Viral Infections. [Available] [May 11, 2016].
  257. Mikirova N, Hunninghake R. Effect of high dose vitamin C on Epstein-Barr viral infection. Med Sci Monit. 2014;20:725-32.
  258. Jahan K, Ahmad K, Ali MA. Effect of ascorbic acid in the treatment of tetanus. Bangladesh Med Res Counc Bull. 1984;10(1):24-8.
  259. Hemilä H, Koivula TT. Vitamin C for preventing and treating tetanus. Cochrane Database Syst Rev. 2008;(2):CD006665.
  260. Gonzalez MJ, Miranda-massari JR, Berdiel MJ, et al. High Dose Intraveneous Vitamin C and Chikungunya Fever: A Case Report. J Orthomol Med. 2014;29(4):154-156.
  261. Chin KY, Ima-nirwana S. Vitamin C and Bone Health: Evidence from Cell, Animal and Human Studies. Curr Drug Targets. 2015;
  262. Kim YA, Kim KM, Lim S, et al. Favorable effect of dietary vitamin C on bone mineral density in postmenopausal women (KNHANES IV, 2009): discrepancies regarding skeletal sites, age, and vitamin D status. Osteoporos Int. 2015;26(9):2329-37.
  263. Hart A, Cota A, Makhdom A, Harvey EJ. The Role of Vitamin C in Orthopedic Trauma and Bone Health. Am J Orthop. 2015;44(7):306-11.
  264. Sun LL, Li BL, Xie HL, et al. Associations between the dietary intake of antioxidant nutrients and the risk of hip fracture in elderly Chinese: a case-control study. Br J Nutr. 2014;112(10):1706-14.
  265. Zhu LL, Cao J, Sun M, et al. Vitamin C prevents hypogonadal bone loss. PLoS ONE. 2012;7(10):e47058.
  266. Torbergsen AC, Watne LO, Wyller TB, et al. Micronutrients and the risk of hip fracture: Case-control study. Clin Nutr. 2015.
  267. Huang YN, Yang LY, Wang JY, Lai CC, Chiu CT, Wang JY. L-Ascorbate Protects Against Methamphetamine-Induced Neurotoxicity of Cortical Cells via Inhibiting Oxidative Stress, Autophagy, and Apoptosis. Mol Neurobiol. 2016.
  268. Ozkan F, Gündüz SG, Berköz M, Hunt AO, Yalın S. The protective role of ascorbic acid (vitamin C) against chlorpyrifos-induced oxidative stress in Oreochromis niloticus. Fish Physiol Biochem. 2012;38(3):635-43.
  269. Altuntas I, Delibas N, Sutcu R. The effects of organophosphate insecticide methidathion on lipid peroxidation and anti-oxidant enzymes in rat erythrocytes: role of vitamins E and C. Hum Exp Toxicol. 2002;21(12):681-5.
  270. Shah SA, Yoon GH, Kim HO, Kim MO. Vitamin C neuroprotection against dose-dependent glutamate-induced neurodegeneration in the postnatal brain. Neurochem Res. 2015;40(5):875-84.
  271. Warner TA, Kang JQ, Kennard JA, Harrison FE. Low brain ascorbic acid increases susceptibility to seizures in mouse models of decreased brain ascorbic acid transport and Alzheimer’s disease. Epilepsy Res. 2015;110:20-5.
  272. Ide K, Yamada H, Umegaki K, et al. Lymphocyte vitamin C levels as potential biomarker for progression of Parkinson’s disease. Nutrition. 2015;31(2):406-8.
  273. Schjoldager JG, Paidi MD, Lindblad MM, et al. Maternal vitamin C deficiency during pregnancy results in transient fetal and placental growth retardation in guinea pigs. Eur J Nutr. 2015;54(4):667-76.
  274. Rafiee B, Morowvat MH, Rahimi-ghalati N. Comparing the Effectiveness of Dietary Vitamin C and Exercise Interventions on Fertility Parameters in Normal Obese Men. Urol J. 2016;13(2):2635-9.
  275. Vijayprasad S, Bb G, Bb N. Effect of vitamin C on male fertility in rats subjected to forced swimming stress. J Clin Diagn Res. 2014;8(7):HC05-8.
  276. De oliveira IJ, De souza VV, Motta V, Da-silva SL. Effects of Oral Vitamin C Supplementation on Anxiety in Students: A Double-Blind, Randomized, Placebo-Controlled Trial. Pak J Biol Sci. 2015;18(1):11-8.
  277. Ebuehi OA, Ogedegbe RA, Ebuehi OM. Oral administration of vitamin C and vitamin E ameliorates lead-induced hepatotoxicity and oxidative stress in the rat brain. Nig Q J Hosp Med. 2012;22(2):85-90.
  278. Tabatabaei-malazy O, Nikfar S, Larijani B, Abdollahi M. Influence of ascorbic acid supplementation on type 2 diabetes mellitus in observational and randomized controlled trials; a systematic review with meta-analysis. J Pharm Pharm Sci. 2014;17(4):554-82.
  279. Maged AM, Torky H, Fouad MA, et al. Role of antioxidants in gestational diabetes mellitus and relation to fetal outcome: a randomized controlled trial. J Matern Fetal Neonatal Med. 2016;:1-6.
  280. Mason SA, Della gatta PA, Snow RJ, Russell AP, Wadley GD. Ascorbic acid supplementation improves skeletal muscle oxidative stress and insulin sensitivity in people with type 2 diabetes: Findings of a randomized controlled study. Free Radic Biol Med. 2016;93:227-38.
  281. Kim HJ, Song W, Jin EH, et al. Combined Low-Intensity Exercise and Ascorbic Acid Attenuates Kainic Acid-Induced Seizure and Oxidative Stress in Mice. Neurochem Res. 2016;41(5):1035-41.
  282. Tutkun E, Arslan G, Soslu R, Ayyildiz M, Agar E. Long-term ascorbic acid administration causes anticonvulsant activity during moderate and long-duration swimming exercise in experimental epilepsy. Acta Neurobiol Exp (Wars). 2015;75(2):192-9.
  283. Richards JC, Crecelius AR, Larson DG, Dinenno FA. Acute ascorbic acid ingestion increases skeletal muscle blood flow and oxygen consumption via local vasodilation during graded handgrip exercise in older adults. Am J Physiol Heart Circ Physiol. 2015;309(2):H360-8.
  284. Chayasirisobhon S. Efficacy of Pinus radiata bark extract and vitamin C combination product as a prophylactic therapy for recalcitrant migraine and long-term results. Acta Neurol Taiwan. 2013;22(1):13-21.
  285. Kim JE, Cho HS, Yang HS, et al. Depletion of ascorbic acid impairs NK cell activity against ovarian cancer in a mouse model. Immunobiology. 2012;217(9):873-81.
  286. Li K, Wang J, Shi M, et al. Prescription consisting of Vitamin C and Baicalin inhibits tumor growth by enhancing the antioxidant capacity in vivo. J BUON. 2015;20(5):1368-72.
  287. Maggini S, Wenzlaff S, Hornig D. Essential role of vitamin C and zinc in child immunity and health. J Int Med Res. 2010;38(2):386-414.
  288. Ströhle A, Hahn A. [Vitamin C and immune function]. Med Monatsschr Pharm. 2009;32(2):49-54.
  289. Huijskens MJ, Walczak M, Sarkar S, et al. Ascorbic acid promotes proliferation of natural killer cell populations in culture systems applicable for natural killer cell therapy. Cytotherapy. 2015;17(5):613-20.
  290. Toliopoulos IK, Simos YV, Daskalou TA, Verginadis II, Evangelou AM, Karkabounas SC. Inhibition of platelet aggregation and immunomodulation of NK lymphocytes by administration of ascorbic acid. Indian J Exp Biol. 2011;49(12):904-8.
  291. Atasever B, Ertan NZ, Erdem-kuruca S, Karakas Z. In vitro effects of vitamin C and selenium on NK activity of patients with beta-thalassemia major. Pediatr Hematol Oncol. 2006;23(3):187-97.
  292. Kim JE, Cho HS, Yang HS, et al. Depletion of ascorbic acid impairs NK cell activity against ovarian cancer in a mouse model. Immunobiology. 2012;217(9):873-81.
  293. Choi MK, Song HJ, Paek YJ, Lee HJ. Gender differences in the relationship between vitamin C and abdominal obesity. Int J Vitam Nutr Res. 2013;83(6):377-84.
  294. Adaramoye O, Ogungbenro B, Anyaegbu O, Fafunso M. Protective effects of extracts of Vernonia amygdalina, Hibiscus sabdariffa and vitamin C against radiation-induced liver damage in rats. J Radiat Res. 2008;49(2):123-31.
  295. Vasilyeval IN, Bespalov VG. [Release of Extracellular DNA after Administration of Radioprotective Combination of α-Tocopherol and Ascorbic Acid]. Radiats Biol Radioecol. 2015;55(5):495-500.
  296. Rostami A, Moosavi SA, Dianat moghadam H, Bolookat ER. Micronuclei Assessment of The Radioprotective Effects of Melatonin and Vitamin C in Human Lymphocytes. Cell J. 2016;18(1):46-51.
  297. Mortazavi SM, Rahimi S, Mosleh-shirazi MA, et al. A Comparative Study on the Life-Saving Radioprotective Effects of Vitamins A, E, C and Over-the-Counter Multivitamins. J Biomed Phys Eng. 2015;5(2):59-66.
  298. Domina EA, Pylypchuk OP, Mikhailenko VM. Destabilization of human cell genome under the combined effect of radiation and ascorbic acid. Exp Oncol. 2014;36(4):236-40.
  299. Fujii Y, Kato TA, Ueno A, Kubota N, Fujimori A, Okayasu R. Ascorbic acid gives different protective effects in human cells exposed to X-rays and heavy ions. Mutat Res. 2010;699(1-2):58-61.
  300. Mhaidat NM, Alzoubi KH, Khabour OF, Tashtoush NH, Banihani SA, Abdul-razzak KK. Exploring the effect of vitamin C on sleep deprivation induced memory impairment. Brain Res Bull. 2015;113:41-7.
  301. Mohammed BM, Fisher BJ, Kraskauskas D, et al. Vitamin C promotes wound healing through novel pleiotropic mechanisms. Int Wound J. 2015;
  302. Murray EL. Burning mouth syndrome response to high-dose vitamin C. Headache. 2014;54(1):169.
  303. Dawood MA, Koshio S, Ishikawa M, Yokoyama S. Immune responses and stress resistance in red sea bream, Pagrus major, after oral administration of heat-killed Lactobacillus plantarum and vitamin C. Fish Shellfish Immunol. 2016;54:266-275.
  304. Sadeghpour A, Alizadehasl A, Kyavar M, et al. Impact of vitamin C supplementation on post-cardiac surgery ICU and hospital length of stay. Anesth Pain Med. 2015;5(1):e25337.
  305. Yang M, Barak OF, Dujic Z, et al. Ascorbic acid supplementation diminishes microparticle elevations and neutrophil activation following SCUBA diving. Am J Physiol Regul Integr Comp Physiol. 2015;309(4):R338-44.
  306. Besse JL, Gadeyne S, Galand-desmé S, Lerat JL, Moyen B. Effect of vitamin C on prevention of complex regional pain syndrome type I in foot and ankle surgery. Foot Ankle Surg. 2009;15(4):179-82.
  307. Lane DJ, Richardson DR. The active role of vitamin C in mammalian iron metabolism: much more than just enhanced iron absorption!. Free Radic Biol Med. 2014;75:69-83.
  308. May JM, Qu ZC, Mendiratta S. Role of ascorbic acid in transferrin-independent reduction and uptake of iron by U-937 cells. Biochem Pharmacol. 1999;57(11):1275-82.
  309. Lane DJ, Chikhani S, Richardson V, Richardson DR. Transferrin iron uptake is stimulated by ascorbate via an intracellular reductive mechanism. Biochim Biophys Acta. 2013;1833(6):1527-41.
  310. Mojić M, Bogdanović pristov J, Maksimović-ivanić D, et al. Extracellular iron diminishes anticancer effects of vitamin C: an in vitro study. Sci Rep. 2014;4:5955.
  311. Angelucci E, Pilo F. Management of iron overload before, during, and after hematopoietic stem cell transplantation for thalassemia major. Ann N Y Acad Sci. 2016;
  312. Grenier D, Huot MP, Mayrand D. Iron-chelating activity of tetracyclines and its impact on the susceptibility of Actinobacillus actinomycetemcomitans to these antibiotics. Antimicrob Agents Chemother. 2000;44(3):763-6.
  313. National Institutes of Health. (2008). Vitamin C Injections Slow Tumor Growth in Mice. [Available]  May 11, 2016].
  314. Hickey, S., & Saul, A. W. (2008). Vitamin C: The real story: The remarkable and controversial healing factor. Laguna Beach, CA: Basic Health Publications.
  315. Jackson CL, Dreaden TM, Theobald LK, et al. Pectin induces apoptosis in human prostate cancer cells: correlation of apoptotic function with pectin structure. Glycobiology. 2007;17(8):805-19.
  316. Zhang L, Ye X, Xue SJ, et al. Effect of high-intensity ultrasound on the physicochemical properties and nanostructure of citrus pectin. J Sci Food Agric. 2013;93(8):2028-36.
  317. Leclere L, Fransolet M, Cambier P, et al. Identification of a cytotoxic molecule in heat-modified citrus pectin. Carbohydr Polym. 2016;137:39-51.
  318. Glinsky VV, Raz A. Modified citrus pectin anti-metastatic properties: one bullet, multiple targets. Carbohydr Res. 2009;344(14):1788-91.
  319. Huang ZL, Liu HY. [Expression of galectin-3 in liver metastasis of colon cancer and the inhibitory effect of modified citrus pectin]. Nan Fang Yi Ke Da Xue Xue Bao. 2008;28(8):1358-61.
  320. Hsieh TC, Wu JM. Changes in cell growth, cyclin/kinase, endogenous phosphoproteins and nm23 gene expression in human prostatic JCA-1 cells treated with modified citrus pectin. Biochem Mol Biol Int. 1995;37(5):833-41.
  321. Leclere L, Fransolet M, Cote F, et al. Heat-modified citrus pectin induces apoptosis-like cell death and autophagy in HepG2 and A549 cancer cells. PLoS ONE. 2015;10(3):e0115831.
  322. Yan J, Katz A. PectaSol-C modified citrus pectin induces apoptosis and inhibition of proliferation in human and mouse androgen-dependent and- independent prostate cancer cells. Integr Cancer Ther. 2010;9(2):197-203.
  323. Hao M, Yuan X, Cheng H, et al. Comparative studies on the anti-tumor activities of high temperature- and pH-modified citrus pectins. Food Funct. 2013;4(6):960-71.!
  324. Jiang J, Eliaz I, Sliva D. Synergistic and additive effects of modified citrus pectin with two polybotanical compounds, in the suppression of invasive behavior of human breast and prostate cancer cells. Integr Cancer Ther. 2013;12(2):145-52.
  325. Wang Y, Nangia-makker P, Balan V, Hogan V, Raz A. Calpain activation through galectin-3 inhibition sensitizes prostate cancer cells to cisplatin treatment. Cell Death Dis. 2010;1:e101.
  326. Hossein G, Keshavarz M, Ahmadi S, Naderi N. Synergistic effects of PectaSol-C modified citrus pectin an inhibitor of Galectin-3 and paclitaxel on apoptosis of human SKOV-3 ovarian cancer cells. Asian Pac J Cancer Prev. 2013;14(12):7561-8.
  327. Inohara H, Raz A. Effects of natural complex carbohydrate (citrus pectin) on murine melanoma cell properties related to galectin-3 functions. Glycoconj J. 1994;11(6):527-32.
  328. Nangia-makker P, Hogan V, Honjo Y, et al. Inhibition of human cancer cell growth and metastasis in nude mice by oral intake of modified citrus pectin. J Natl Cancer Inst. 2002;94(24):1854-62.
  329. Pienta KJ, Naik H, Akhtar A, et al. Inhibition of spontaneous metastasis in a rat prostate cancer model by oral administration of modified citrus pectin. J Natl Cancer Inst. 1995;87(5):348-53.
  330. Platt D, Raz A. Modulation of the lung colonization of B16-F1 melanoma cells by citrus pectin. J Natl Cancer Inst. 1992;84(6):438-42.
  331. Liu HY, Huang ZL, Yang GH, Lu WQ, Yu NR. Inhibitory effect of modified citrus pectin on liver metastases in a mouse colon cancer model. World J Gastroenterol. 2008;14(48):7386-91.
  332. Hayashi A, Gillen AC, Lott JR. Effects of daily oral administration of quercetin chalcone and modified citrus pectin on implanted colon-25 tumor growth in Balb-c mice. Altern Med Rev. 2000;5(6):546-52.
  333. Ma Z, Han Q, Wang X, Ai Z, Zheng Y. Galectin-3 Inhibition Is Associated with Neuropathic Pain Attenuation after Peripheral Nerve Injury. PLoS ONE. 2016;11(2):e0148792.
  334. Abu-elsaad NM, Elkashef WF. Modified citrus pectin stops progression of liver fibrosis by inhibiting galectin-3 and inducing apoptosis of stellate cells. Can J Physiol Pharmacol. 2016;94(5):554-62.
  335. Kolatsi-joannou M, Price KL, Winyard PJ, Long DA. Modified citrus pectin reduces galectin-3 expression and disease severity in experimental acute kidney injury. PLoS ONE. 2011;6(4):e18683.
  336. Chen CH, Sheu MT, Chen TF, et al. Suppression of endotoxin-induced proinflammatory responses by citrus pectin through blocking LPS signaling pathways. Biochem Pharmacol. 2006;72(8):1001-9.
  337. Arad U, Madar-balakirski N, Angel-korman A, et al. Galectin-3 is a sensor-regulator of toll-like receptor pathways in synovial fibroblasts. Cytokine. 2015;73(1):30-5.
  338. Eliaz I, Hotchkiss AT, Fishman ML, Rode D. The effect of modified citrus pectin on urinary excretion of toxic elements. Phytother Res. 2006;20(10):859-64.
  339. Zhao ZY, Liang L, Fan X, et al. The role of modified citrus pectin as an effective chelator of lead in children hospitalized with toxic lead levels. Altern Ther Health Med. 2008;14(4):34-8.
  340. Eliaz I, Weil E, Wilk B. Integrative medicine and the role of modified citrus pectin/alginates in heavy metal chelation and detoxification–five case reports. Forsch Komplementmed. 2007;14(6):358-64.
  341. Vergaro G, Prud’homme M, Fazal L, et al. Inhibition of Galectin-3 Pathway Prevents Isoproterenol-Induced Left Ventricular Dysfunction and Fibrosis in Mice. Hypertension. 2016;67(3):606-12.
  342. Martínez-martínez E, López-Ándres N, Jurado-lópez R, et al. Galectin-3 Participates in Cardiovascular Remodeling Associated With Obesity. Hypertension. 2015;66(5):961-9.
  343. Martínez-martínez E, Calvier L, Fernández-celis A, et al. Galectin-3 blockade inhibits cardiac inflammation and fibrosis in experimental hyperaldosteronism and hypertension. Hypertension. 2015;66(4):767-75.
  344. Calvier L, Martinez-martinez E, Miana M, et al. The impact of galectin-3 inhibition on aldosterone-induced cardiac and renal injuries. JACC Heart Fail. 2015;3(1):59-67.
  345. Mackinnon AC, Liu X, Hadoke PW, Miller MR, Newby DE, Sethi T. Inhibition of galectin-3 reduces atherosclerosis in apolipoprotein E-deficient mice. Glycobiology. 2013;23(6):654-63.
  346. Ramachandran C, Wilk BJ, Hotchkiss A, Chau H, Eliaz I, Melnick SJ. Activation of human T-helper/inducer cell, T-cytotoxic cell, B-cell, and natural killer (NK)-cells and induction of natural killer cell activity against K562 chronic myeloid leukemia cells with modified citrus pectin. BMC Complement Altern Med. 2011;11:59.
  347. Martínez-martínez E, Calvier L, Rossignol P, et al. Galectin-3 inhibition prevents adipose tissue remodelling in obesity. Int J Obes (Lond). 2016;
  348. Dourado GK, Stanilka JM, Percival SS, Cesar TB. Chemopreventive Actions of Blond and Red-Fleshed Sweet Orange Juice on the Loucy Leukemia Cell Line. Asian Pac J Cancer Prev. 2015;16(15):6491-9.
  349. So FV, Guthrie N, Chambers AF, Moussa M, Carroll KK. Inhibition of human breast cancer cell proliferation and delay of mammary tumorigenesis by flavonoids and citrus juices. Nutr Cancer. 1996;26(2):167-81.
  350. Tanaka T, Kohno H, Murakami M, et al. Suppression of azoxymethane-induced colon carcinogenesis in male F344 rats by mandarin juices rich in beta-cryptoxanthin and hesperidin. Int J Cancer. 2000;88(1):146-50.;2-I/full
  351. Miyagi Y, Om AS, Chee KM, Bennink MR. Inhibition of azoxymethane-induced colon cancer by orange juice. Nutr Cancer. 2000;36(2):224-9.
  352. Tanaka T, Tanaka T, Tanaka M, Kuno T. Cancer chemoprevention by citrus pulp and juices containing high amounts of β-cryptoxanthin and hesperidin. J Biomed Biotechnol. 2012;2012:516981.
  353. Oikeh EI, Omoregie ES, Oviasogie FE, Oriakhi K. Phytochemical, antimicrobial, and antioxidant activities of different citrus juice concentrates. Food Sci Nutr. 2016;4(1):103-9.
  354. Buscemi S, Rosafio G, Arcoleo G, et al. Effects of red orange juice intake on endothelial function and inflammatory markers in adult subjects with increased cardiovascular risk. Am J Clin Nutr. 2012;95(5):1089-95.
  355. Ko SH, Choi SW, Ye SK, Cho BL, Kim HS, Chung MH. Comparison of the antioxidant activities of nine different fruits in human plasma. J Med Food. 2005;8(1):41-6.
  356. Constans J, Bennetau-pelissero C, Martin JF, et al. Marked antioxidant effect of orange juice intake and its phytomicronutrients in a preliminary randomized cross-over trial on mild hypercholesterolemic men. Clin Nutr. 2015;34(6):1093-100.
  357. Lee SG, Yang M, Wang Y, et al. Impact of orange juice consumption on bone health of the U.S. population in the national health and nutrition examination survey 2003-2006. J Med Food. 2014;17(10):1142-50.
  358. Deyhim F, Garica K, Lopez E, et al. Citrus juice modulates bone strength in male senescent rat model of osteoporosis. Nutrition. 2006;22(5):559-63.
  359. Pittaluga M, Sgadari A, Tavazzi B, et al. Exercise-induced oxidative stress in elderly subjects: the effect of red orange supplementation on the biochemical and cellular response to a single bout of intense physical activity. Free Radic Res. 2013;47(3):202-11.
  360. Aptekmann NP, Cesar TB. Orange juice improved lipid profile and blood lactate of overweight middle-aged women subjected to aerobic training. Maturitas. 2010;67(4):343-7.
  361. Escudero-lópez B, Berná G, Ortega Á, et al. Consumption of orange fermented beverage reduces cardiovascular risk factors in healthy mice. Food Chem Toxicol. 2015;78:78-85.
  362. Zanotti simoes dourado GK, De abreu ribeiro LC, Zeppone carlos I, Borges césar T. Orange juice and hesperidin promote differential innate immune response in macrophages ex vivo. Int J Vitam Nutr Res. 2013;83(3):162-7.
  363. Wang Y, Lloyd B, Yang M, et al. Impact of orange juice consumption on macronutrient and energy intakes and body composition in the US population. Public Health Nutr. 2012;15(12):2220-7.
  364. O’neil CE, Nicklas TA, Rampersaud GC, Fulgoni VL. 100% orange juice consumption is associated with better diet quality, improved nutrient adequacy, decreased risk for obesity, and improved biomarkers of health in adults: National Health and Nutrition Examination Survey, 2003-2006. Nutr J. 2012;11:107.
  365. Salamone F, Li volti G, Titta L, et al. Moro orange juice prevents fatty liver in mice. World J Gastroenterol. 2012;18(29):3862-8.
  366. Azik M. Phytochemicals in citrus. Florida Department of Citrus. 2010. Available: [February 5, 2017].
  367. Better Health Publishing. New Research: Modified Citrus Pectin – A potent anti-cancer therapy. PR Newswire. 2013.
  368. Stone I. On the genetic etiology of scurvy. Acta Genet Med Gemellol (Roma). 1966;15(4):345-50.
  369. Jiao Y, Wilkinson J, Di X, et al. Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator. Blood. 2009;113(2):462-9.