If 'Blue Light' is Bad For Us, Which Type of Light is Good?

Science Says: 'Blue Light' is Bad for Us, Green Light May Be Good

The good and bad effects of light exposure have “come to light” in recent studies that have
investigated the positive effects of sunlight on health and the negative effects of exposure to artificial light, particularly at night.

While full-spectrum lighting mimics the effects of sunlight with its full complement of colors, most modern artificial lighting varies in its wavelengths.

Indeed, the significant blue component of light from sources such as computer monitors and other electronic device screens (particularly light-emitting diodes, or LEDS) has been blamed for an array of symptoms including eye strain, headaches, and insomnia.

But while blue light appears to be harmful in some respects, green light is a horse of a different color.

It’s been said that living in an area with a high amount of green space can reduce the impact of stressful life events.1 Other research has found an association between the quantity and quality of green areas and streetscape greenery on indicators of health.2 Another study revealed what appears to be a protective effect of access to urban green space against anxiety and mood disorders.3 According to an article in the February 1, 2018 issue of Bioscience, several biologically plausible theories have been proposed to explain this effect. These include attention-restoration theory, stress-reduction theory, and biophilia theory.4 Could something as simple as color also play a role?

Could Green Light Relive Pain?

In recent research, Mohab M. Ibrahim and colleagues at the University of Arizona found that exposure to green LED light increases pain tolerance in rats, and that when the rodents were fitted with green contact lenses, a pain-relieving effect was also observed.5

The journey to Dr. Ibrahim’s discovery of the benefit of green light began with his brother. His brother suffered from headaches and reported feeling better just by going outside to sit among the trees. "Sometimes I get headaches myself, so I go to a park and sit there, and I do feel better,” Dr. Ibrahim stated. “I thought, why is this happening? It could be because it's quiet. You're meditating, and life slows down, but I can also be quiet in my office, and it doesn't take the headaches away. Then I thought maybe it's the trees. So, I thought about what trees do. They could be releasing some sort of chemical in the air, or maybe it's just their color, green, which is associated with most trees."6

"While the pain-relieving qualities of green LED are clear, exactly how it works remains a puzzle," commented Rajesh Khanna, University of Arizona, Associate Professor of Pharmacology who is a senior author of the research report coauthored by Dr. Ibrahim. "Early studies show that green light is increasing the levels of circulating endogenous opioids, which may explain the pain-relieving effects. Whether this will be observed in humans is not yet known and needs further work."

The Best Lighting for Migraine Sufferers

The pain-relieving effect of green light could help migraine sufferers. Individuals experiencing migraines are particularly sensitive to light, prompting many of them to seek recovery in darkened rooms, which involves significant time spent absent from work or other duties. Research conducted by Rami Burstein, PhD, of Harvard Medical School, and colleagues, revealed that while blue light increases the pain of migraine, exposure to green light could reduce pain in approximately 20% of the patients. The group of scientists discovered that, of all colors, green light generated the smallest electric signals in the retina of the eye and in the brain’s cortex. Further investigation revealed that neurons in the thalamus of the brain, which transmits information concerning light from the eye to the cortex, are most responsive to blue light and least responsive to green.7

These findings helped the investigators conclude that the most photophobic blue light activates more neurons and causes a stronger response than the least photophobic green light. White light, which is more photophobic than green light, activates neurons more powerfully than green light, but less intensely than bluelight. “Therapeutically, filtering out all but green light may prove beneficial for the reduction of photophobia and potentially the headache intensity”, write the study investigators.

Effects of Light on Sleep

For those wishing to avoid some of the harmful effects of excessive blue light exposure, a variety of blue-blocking sunglasses are available as well as protective lenses that can be worn during the day. Computer screen protectors and applications that reduce exposure to blue light in the evening can help protect the eyes and improve sleep. It is recommended to take a break from bright light exposure at least one hour before going to bed in order to improve the release of melatonin, a hormone that facilitates sleep.

Related Article: How Much Melatonin Should I Take?  

A study that examined the effects of blue or green light on sleep found that blue light kept mice awake longer while green light was conducive to sleep. Researchers Violet Pilorz and colleagues determined that a light sensor in the eye known as melanopsin is critical to the response.8 And while both blue and green light increased corticosterone levels compared to animals exposed to no light, levels were higher among mice exposed to blue light than among those exposed to green light.

“These results reinforce the idea that blue light exerts a powerful alerting effect compared to green light,” write Patrice Bourgin and Jeffrey Hubbard in an article in the same journal. The authors point out that the possibility to use different wavelength compositions to stimulate alertness or help sleep may lead to additional indications of light therapy as a complementary approach to help patients with insomnia or excessive daytime sleepiness.9

In discussing the article by Pilorz and colleagues, the authors explain that the findings open the need for a better understanding of melanopsin-based phototransduction. Based on their research results, color wavelength is another aspect of environmental illumination that should be considered in addition to photon density, duration of exposure, and time of day when designing lighting to improve human health and well-being.


  1. van den Berg AE, et al. Soc Sci Med. 2010 Apr;70(8):1203-10.
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  6. https://uanews.arizona.edu/story/treatment-pain-gets-green-light
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  8. Pilorz V, et al. PLoS Biol. 2016 Jun 8;14(6):e1002482.
  9. Bourgin P, et al. PLoS Biol. 2016 Aug 15;14(8):e2000111.

Noble Nobiletin: Top 5 Health Benefits from this Citrus Flavonoid

Noble Nobiletin: Top 5 Health Benefits from this Citrus Flavonoid

Nobiletin, like tangeretin, is a type of flavonoid known as a polymethoxylated flavone, which is
found in citrus fruit, including its peel. In addition to its antioxidant property, nobiletin has antitumor, anti-inflammatory and other effects.

1) Anti-Inflammatory

Research has determined that nobiletin’s anti-inflammatory effect is similar to that of corticosteroid drugs and that its upregulation of the matrix metalloproteinase inhibitor TIMP-1 is a unique action. (Matrix metalloproteinases are enzymes responsible for the degradation of collagen, one of the main structural components of connective tissue.) In rats with induced rheumatoid arthritis, treatment with nobiletin lowered proinflammatory cytokines that included interleukin-1 beta, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), while downregulating the expression of the p38/nuclear factor kappa beta signaling pathway (involved in inflammation) in the synovial membrane.1 Nobiletin has also shown an ability to prevent life-threatening endotoxic shock, a severe response generated in the body in response to inflammatory molecules.2 Aside from its ability to inhibit IL-6 and TNF-alpha, research has shown that nobiletin inhibits the production of HMGB1, a mediator of endotoxin lethality with significant ability to indirectly stimulate inflammation.

In rabbit synovial fibroblasts and joint chondrocytes, nobiletin was the most effective of six flavonoids tested at suppressing the expression of matrix metalloproteinases. Nobiletin also reduced the production of the inflammatory mediator prostaglandin E2 (PGE2). The authors concluded, based on these results, that nobiletin is a novel anti-inflammatory candidate with the potential to inhibit PGE2 production and matrix degradation of the articular cartilage in osteoarthritis and rheumatoid arthritis.3

2) Anti-Cancer

As is the case with tangeretin, nobiletin has been associated with anticancer effects. In cancer cells, nobiletin and other citrus flavonoids have shown a protective effect against invasion. An experiment that tested the effects of four anti-invasive agents in seven human brain tumor-derived cell lines revealed that nobiletin was among the flavonoids with the greatest ability to inhibit invasion, migration, and adhesion in four of the cell lines and was also the most effective at downregulating the secretion of matrix metalloproteinases.4 In human squamous cell carcinoma cells, nobiletin inhibited cell growth after five days of administration at several concentrations that were tested.5 In mouse skin exposed to the tumor-promoting compound TPA, nobiletin inhibited two stages of skin inflammation, the expression of cyclooxygenase-2 (COX-2, an enzyme associated with inflammation) and the release of prostaglandin E2. Nobiletin helped inhibit skin tumor formation induced by the carcinogens DMBA and TPA by decreasing the number of tumors per mouse by 61.2% to 75.7%. These findings suggest that nobiletin could be a new chemopreventive agent in the tumorigenesis associated with inflammation.6

In rats given azoxymethane, a compound that induces aberrant crypt foci of the colon (a precursor of colon cancer), nobiletin given for five weeks prior to azoxymethane administration lowered the formation of aberrant crypt foci as well as prostaglandin E2 in the colon mucosa.7 In other research, which evaluated nobiletin’s effect in human colorectal cancer cells, nobiletin was shown to induce apoptosis (programmed cell death).8

In immunodeficient mice, administration of nobiletin was associated with a reduction in the mass and number of peritoneal dissemination nodules from a stomach cancer cell line in comparison with treatment with a control substance, suggesting its use as a drug to combat metastasis of gastric cancer.9

Research has found an increase in the uptake of the chemotherapeutic drugs vincristine in human myelogenous leukemia cells, and vinblastine in human colorectal cells in association with the administration of nobiletin. This has led to the conclusion that nobiletin and other methoxyflavones have potential as agents for reversing multidrug resistance in chemotherapy. When consumed regularly along with the drug atorvastatin, nobiletin has shown a protective effect against colon cancer in rats treated with a carcinogen by modulating cellular signaling regulators associated with inflammation, cell proliferation, cell cycle progression, apoptosis, angiogenesis and metastasis.

3) Prevents Clotting

Another area of benefit for nobiletin is in the inhibition of platelet adhesiveness and clot formation, that was confirmed in research involving mice. Investigation of nobiletin’s ability to modulate platelet function revealed mechanisms that include suppression of platelet aggregation, calcium mobilization, clot formation and more.10

4) Supports the Brain

Recent research suggests a protective effect for nobiletin against neurotoxic neuronal calcium overload. J. H. Lee and colleagues at Jeju National University reported that mitochondrial calcium overload is crucial in determining neuronal cell survival and death, processes that have been implicated in neurodegenerative diseases.11

In human stem cell-derived neurons that generate an excess of amyloid beta, and are used to study Alzheimer’s disease, nobiletin significantly reduced the amyloid beta content in the neurons as well as the extracellular amyloid beta. According to the researchers involved in the study, nobiletin appears to be a promising new prophylactic agent or functional food for Alzheimer’s disease.12 A review of nobiletin’s neuroprotective actions in Alzheimer’s and Parkinson’s disease noted that the flavonoid has been demonstrated to modify cholinergic deficits, reduce amyloid beta accumulation, help heal injury due to low blood flow, prevent tau protein hyperphosphorylation, and more.13 In a rat model of Parkinson’s disease, treatment with nobiletin protected dopaminergic neurons in the substantia nigra of the brain in addition to other benefits.14

5) Preservation and Regulation

Other potential uses for nobiletin include those of a food preservative; in cataract prevention; as a sunscreen; as a preventive agent and treatment for nonalcoholic fatty liver; as a therapy to prevent bone loss in postmenopausal women; and as a nutritional therapy for circadian clock disorders. Concerning the latter, the authors of an article in Cell Metabolism concluded that, based on their work, nobiletin activates RORs (retinoid acid receptor-related orphan receptors) and protects against metabolic syndrome in a clock-dependent manner. They predicted that their proof-of-principle study will accelerate the future use of nobiletin for other diseases, such as mood and sleep disorders, and for aging, in which the circadian amplitude is changed.”15


Nobiletin is a polymethoxyflavonoid that occurs exclusively in citrus fruits and has shown many benefits, including its ability to induce the differentiation of mouse myeloid leukemia cells, to exhibit antiproliferative activity toward a human squamous cell carcinoma cell line, to show anti-mutagenic activity, and to suppress the release pf matrix metalloproteinase-9 and prostaglandin E2 release. The authors of a study reported that nobiletin suppressed the combined endotoxin and cytokine-induced expression of nitric oxide synthase and cyclooxygenase-2 proteins, and thanks to these and several other benefits, they concluded that nobiletin emerges as a promising anti-inflammatory and/or chemopreventive agent.17

In addition to these prominent anticancer and anti-inflammatory benefits, nobiletin shows promise in other areas. Since not everyone consumes citrus fruit, a stand-alone nobiletin supplement is something we look forward to!


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  13. Braidy N et al. CNS Neurol Disord Drug Targets. 2017;16(4):387-397.
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  15. He B et al. Cell Metab. 2016 Apr 12;23(4):610-21.
  16. Murakami A et al. Biosci Biotechnol Biochem. 2001 Jan;65(1):194-7.

Tangerines and Tangeretin: The Appeal Is in the Peel

Tangerines and Tangeretin: The Appeal Is in the Peel

Tangerines are a citrus fruit that are smaller and sweeter than oranges. Named for Tangier, Morocco, where they were once sourced, the fruit is an excellent source of vitamin C and fiber. The frequently discarded peel of citrus fruit is known for its beneficial bioflavonoid content. Tangerine peel contains a significant amount of the polymethoxy flavonoid tangeretin, which has antioxidant and other beneficial effects in the body.

Researchers have studied tangeretin in cells, animals and humans. We will explore some of their findings.

Heath Benefits of Tangeretin

Tangeretin has been investigated regarding potential benefits in a number of health areas. In a mouse model of bone loss, tangeretin suppressed the formation of osteoclasts (which absorb bone tissue) induced by an inflammatory compound.1 Research in rodents has also shown effects against asthma.2 And in rats with chronic kidney disease, tangeretin’s antioxidant and anti-inflammatory effects improved renal function, as well as memory and cognitive impairments.3

In hamsters with diet-induced high cholesterol levels, polymethoxylated flavones that included tangeretin were associated with a reduction in serum total and very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) cholesterol.4 In human liver cells, tangeretin reduced apolipoprotein B, cholesterol and triglyceride synthesis.5 Other research has shown that tangeretin significantly inhibited proliferation and migration of rat aortic smooth muscle cells without inducing cell death.6 This finding indicates a potential use for tangeretin in the prevention and treatment of vascular diseases, including atherosclerosis. Tangeretin has also shown an ability to inhibit platelet adhesion and clot formation.7

Other data show that tangeretin can increase uptake of glucose in mouse fat cells via three pathways, which might explain the antidiabetic effect of this type of flavonoid.8 More research involving fat cells has found that tangeretin increased the secretion of adiponectin (an insulin-sensitizing factor), while decreasing insulin-resistance factor MCP1.9 In diabetic rats, tangeretin lowered glucose and hemoglobin A1c while helping normalize the activity of enzymes involved in carbohydrate metabolism, with effects comparable to that of antidiabetic drug glibenclamide.10 In vitro and in mice, tangeretin was found to exert antidiabetic effects through activation of AMPK, an enzyme found in every cell of the body that decreases with aging.11 AMPK promotes healthy cellular metabolism and encourages the body to burn stored abdominal fat. Tangeretin was also shown to inhibit the formation of new fat cells.12

Like many flavonoids, tangeretin has shown anticancer effects. In 1991, it was discovered that, of all citrus flavonoids tested, tangeretin had the greatest inhibitory effect against tumor invasion.13 In human squamous cell carcinoma, tangeretin inhibited cell growth five and seven days after treatment at all concentrations tested, while two other flavonoids showed no effect.14 In human leukemia cells, tangeretin induced apoptosis (programmed cell death), with no toxicity in normal white blood cells.15

Tangeretin also showed antiproliferative activity against human lung carcinoma, mouse melanoma, human T-cell leukemia, and human gastric cancer cells that was at least 10 times of that exerted against normal cell lines.16 In addition, tangeretin can inhibit growth of human colorectal carcinoma cells by blocking cell cycle progression.17 An ability to inhibit mutagenesis and metastasis are other anticancer mechanisms attributed to tangeretin.18 In an animal model of lung metastatic melanoma, tangeretin lowered the percentage of three indexes of metastasis in comparison with a control substance.19

“There are two general approaches to the use of flavonoids or other polyphenols as cancer chemopreventive agents,” Thomas Walle writes in an article titled, Methoxylated flavones, a superior cancer chemopreventive flavonoid subclass? “One is to choose diets rich in such compounds, including verification of their possible effectiveness followed by attempts to deduce potential mechanisms . . . The other more common and simplest approach is to identify dietary components with potential cancer chemopreventive properties through testing of individual compounds first in vitro and then in vivo. The ultimate goal here is to arrive at food supplements, which may serve to reinforce the dietary contribution.”20

Unique and Synergistic Properties

Unlike many compounds, tangeretin can cross the blood-brain barrier to exert its effects in the brain. In a rat model of Parkinson’s disease in which the disease was induced by injection of a neurotoxin, tangeretin helped protect against loss of brain cells involved in the production of dopamine and decrease in brain striatal dopamine content, suggesting its potential use as a neuroprotective agent.21 Another study involving a rat model of the disease resulted in improved motor function and cognition and a reduction in memory impairment in animals treated with tangeretin. Tangeretin-treated animals experienced protection against dopaminergic degeneration and hippocampal neuron loss, and had lower expression of inflammatory mediators and cytokines.22 In a study that evaluated the effects of tangerine peel extract or a combination of the flavonoids tangeretin, hesperidin and nobiletin, both inhibited inflammation induced by lipopolysaccharide administration in cultured microglia cells (which are the primary immune cells of the central nervous system), leading the authors of the report to conclude that tangerine peel possesses a potent anti-neuroinflammatory capacity.23 Research has also uncovered potent antioxidant effects for tangeretin in microglia.24

A Fruitful Future for Tangeretin

Tangeretin has been shown to: decrease cholinergic deficits; reduce the abnormal accumulation of amyloid-beta; reverse N-methyl- D-aspartate receptor hypofunction; improve ischemic injury; inhibit hyperphosphorylation of tau protein; and more, according to N. Braidy and colleagues in the journal CNS & Neurological Disorders Drug Targets. The authors suggest that “tangeretin and other citrus flavonoids could represent beneficial drug candidates for the treatment and prevention of Alzheimer's and Parkinson's disease.”25 Future research will add evidence to these and other potential targeted uses for tangeretin.

The chemical structure of tangeretin indicates potential for superior oral bioavailability.26 Research in mice has shown that tangeretin does not adversely affect the function of major organs.27 Women treated with the drug tamoxifen for cancer should avoid supplementing with tangeretin.28


  1. Tominari T et al. J Pharmacol Sci. 2012;119(4):390-4.
  2. Liu et al. Braz J Med Biol Res. 2017 Jul 20;50(8):e5991
  3. Wu et al. Inflammopharmacology. 2018 Feb;26(1):119-132.
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  10. Sundaram R et al. Phytomedicine. 2014 May 15;21(6):793-9.
  11. Kim et al Mol Cell Endocrinol. 2012 Jul 6;358(1):127-34
  12. He YF et al. Genet Mol Res. 2015 Oct 29;14(4):13642-8.
  13. Bracke M et al. Clin Exp Metastasis. 1991 Jan-Feb;9(1):13-25.
  14. Kandaswami C et al. Cancer Lett. 1991 Feb;56(2):147-52.
  15. Hirano T et al. Br J Cancer. 1995 Dec;72(6):1380-8.
  16. Kawaii S et al. Biosci Biotechnol Biochem. 1999 May;63(5):896-9.
  17. Pan MH et al. Carcinogenesis. 2002 Oct;23(10):1677-84.
  18. Calomme M et al. Planta Med. 1996 Jun;62(3):222-6.
  19. Conesa DM et al. J Agric Food Chem. 2005 Aug 24;53(17):6791-7.
  20. Walle T et al. Semin Cancer Biol. 2007 Oct;17(5):354-62.
  21. Datla KP et al. Neuroreport. 2001 Dec 4;12(17):3871-5.
  22. Yang JS et al. Inflammopharmacology. 2017 Aug;25(4):471-484.
  23. Ho SC et al. Food Chem Toxicol. 2014 Sep;71:176-82.
  24. Lee et al. J Neuroimmune Pharmacol. 2016 Jun;11(2):294-305
  25. Braidy N et al. CNS Neurol Disord Drug Targets. 2017;16(4):387-397.
  26. Walle T et al. Semin Cancer Biol. 2007 Oct;17(5):354-62.
  27. In Vivo. 2005 Jan-Feb;19(1):103-7.
  28. Depypere HT et al. Eur J Cancer. 2000 Sep;36 Suppl 4:S73.

Mononucleosis in Adults: What You Need to Know

Holli (Lapes) Ryan RD, LD/N

Mononucleosis in Adults: What You Need to Know

Mononucleosis, commonly referred to as “mono” for short, is often referred to as “the kissing disease” because it can be transmitted via saliva. Although mono is a common viral infection among children and teenagers, adults can get it, too. So, if you’re an adult and find yourself with symptoms of mono (extreme fatigue, sore throat, fever, swollen lymph nodes, headache and body aches, swollen spleen and/or liver), here is some helpful information for you to know.

Know the Cause

Epstein Barr Virus (EBV) is typically the cause of a mononucleosis infection, but it could also be caused by Cytomegalovirus (CMV). 1 As with all health conditions, proper diagnosis is key. If your doctor suspects mono, you may be given a mononucleosis spot (or Monospot) test, which rapidly looks for EBV antibodies. A blood test is the best way to confirm the diagnosis and to find out what type of virus caused the infection.

Lab Tests for Diagnosis

Your doctor may order the following tests to diagnose your condition:

  • Monospot test
  • Epstein Barr viral capsid antigen (VCA) immunoglobulins G or M (IgG or IgM) antibodies
  • CMV IgG or IgM antibodies
  • Liver enzymes alanine transaminase (ALT) and aspartate transaminase (AST)
  • Ultrasound of spleen
IgM and IgG antibodies are proteins produced by your immune system to fight an infection. IgMs are the first ones to appear and do not persist in the blood for more than a few weeks. A high level of IgMs indicates a current or recent (acute) infection. IgGs appear later and will persist for the rest of your life to protect you against future infections.

Because enlarged organs may occur with mono, your doctor may order an ultrasound of the spleen to check its size.1 Elevated liver enzymes (ALT and AST) showing up on your blood test can also be a sign of mono infection.

Treatment for Adults with Mono

Proper diagnosis is key so you can receive proper treatment. Importantly, mono is not caused by bacteria, but by a virus. As you may know, antibiotic overuse and misuse is widespread, and antibiotics may be wrongly prescribed to someone with a mono infection. Plus, because you are an adult, your doctor may not suspect mono simply because of your age. Also, antibiotics such as amoxicillin and azithromycin are contraindicated for someone who has mono because they could cause a severe rash.2

So, what IS the treatment for mono? Treatment involves rest, fluids, and over-the-counter pain and fever-reducing medicines to ease symptoms. Some doctors may prescribe steroids for excessive swelling. You could also consider adding some nutrients to combat the virus. Help your immune system fight the virus with reishi mushroom3, vitamin C4, and quercetin5.

Nutrient Depletion and Side Effects from Medications

If you were given steroids such as prednisone to help with the inflammation in your body caused by the infection, your body may have become depleted of important minerals such as chromium and calcium.6

The adaptogenic herb ashwagandha can be helpful to promote mental energy and concentration.7 If appropriate for the individual (based on factors such as their medical history and age) a short-term, low dose of the hormone dehydroepiandrosterone (DHEA) can be beneficial as well.8

If you were given antibiotics for this viral infection, you’ll want to restore the good bacteria in your body by taking probiotics. Vitamin K, which has a lot of health benefits, is another good supplement to add in if you were recently on antibiotics because the good bacteria in your gut that were just killed off, produce some vitamin K.9

If you were given antibiotics and developed a rash because of it, you can soothe it with topical applications of witch hazel, aloe, and oatmeal baths. Don’t shower with hot water as it will irritate the rash. Although vitamin C is one’s best friend during this time, avoid citrus fruits and strawberries as these may also irritate the rash. Instead, choose other sources of vitamin C, such as broccoli, or take a vitamin C supplement. You can also consider intravenous therapy with high-dose vitamin C.10

Nutrition and Wellness

The fatigue you’re experiencing could get even worse without adequate hydration. Choose a coconut water with no added sugars as a source of both hydration and minerals (which also serve as electrolytes for heart function and more). Caffeine is never really a good idea when you are sick, but you should especially avoid it while you have mono because of your elevated heart rate due to the illness. Instead of caffeinated tea or coffee, choose decaffeinated tea or plain hot water with lemon and honey. No alcohol either since it may delay the recovery of the immune system and would further elevate liver enzymes.

To soothe your inflamed tonsils, hot liquids are key. Sip on hot bone broth for the protein content, soothing temperature, and minerals. Since your appetite may not be existent, bone broth can help you meet your protein needs. Don’t forget about good old chicken soup for the soul as well. You could also gargle with salt water.

Exclude dairy products and refined grains during this time, especially if you are taking antibiotics, because the simple carb sugars and refined grains can feed the bad bacteria, and dairy tends to contribute to congestion and mucus production. I also suggest having plenty of fresh produce on deck to make nutritious meals.



Refined Grains and Sugar Soup and/or Bone Broth

Water and/or Coconut Water


Fruits and Vegetables

Hot Liquids

About the author: Holli (Lapes) Ryan RD, LD/N is a Social Media Content Specialist at Life Extension. She is a Registered and Licensed Dietitian Nutritionist residing in the South Florida area. Holli believes that quality dietary supplements are an essential tool that have a variety of applications from maintaining good health to managing chronic disease.

  1. https://emedicine.medscape.com/article/784513-clinical
  2. https://www.omicsonline.org/open-access/antibiotic-induced-cutaneous-rash-in-infectious-mononucleosis-overview-ofthe-literature-2155-6121-1000222.php?aid=61748
  3. http://www.lifeextension.com/Magazine/2014/8/Fight-Immune-Decline-With-Reishi/Page-01
  4. http://www.lifeextension.com/Newsletter/2014/6/High-Dose-Vitamin-C-Reduces-Epstein-Barr-Viral-Infection/Page-01
  5. http://www.lifeextension.com/Magazine/2012/9/Quercetin-Broad-Spectrum-Protection/Page-02
  6. https://www.uofmhealth.org/health-library/hn-10000612
  7. http://www.lifeextension.com/Magazine/2016/8/Fight-Stress-and-Support-Adrenals-with-Adaptogens/Page-01
  8. http://www.lifeextension.com/Magazine/2004/3/cover_dhea/Page-04
  9. https://www.researchgate.net/publication/21663877_The_production_of_menaquinones_Vitamin_K2_by_intestinal_bacteria_and_their_role_in_maintaining_coagulation_homeostasis
  10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015650/

Does Calorie Restriction Extend Human Life?

Calorie restriction (CR), a technique that entails significantly reducing the number of calories
consumed while simultaneously ensuring the intake of an optimal amount of nutrients, has been demonstrated to extend the life span of almost every species of animal in which it has been tested. But will it extend human life?

Historical Case Study

The earliest record of successful human calorie restriction was that documented by Luigi Cornaro, a Venetian nobleman born in 1467. After finding himself in ill health after the age of 35 because of his excessive eating and drinking, he took the advice of his physicians and began restricting his diet to the equivalent of 12 ounces of food and 14 ounces of wine per day. His writings on the subject, which have been translated and published under several titles including Discourses on the Temperate Life, described his successful regimen at four successive ages.

“Being arrived at my ninety-fifth year, God be praised, and still finding myself sound and hearty, content and cheerful, I never cease to thank the Divine Majesty for so great a blessing, considering the usual condition of old men,” Cornaro wrote in his fourth and final discourse. “These scarcely ever attain the age of seventy, without losing health and spirits, and growing melancholy and peevish. Moreover, when I remember how weak and sickly I was between the ages of thirty and forty, and how from the first, I never had what is called a strong constitution; I say, when I remember these things, I have surely abundant cause for gratitude, and though I know I cannot live many years longer, the thought of death gives me no uneasiness; I, moreover, firmly believe that I shall attain to the age of one hundred years.”1

CR Research in the 1990’s

Fast forward to 1991. A closed, self-supporting ecological system in the Arizona desert known as Biosphere 2 was the site of a study (supported in part by the National Institutes of Health and the Life Extension Foundation) involving four men and four women whose challenges in food cultivation necessitated a calorie restricted diet.2 One of those men was the famed calorie restriction researcher and advocate, gerontologist Roy L. Walford, MD.

Calorie intake averaged 1,784 for the first six months and increased to just 2,000 calories for the remainder of the two-year experiment. This resulted in a decline in body mass index of 19% among the male participants and 13% among the women.

During the course of the study, blood and urine were collected and analyzed every eight weeks. In comparison with values measured before entry into the Biosphere, some remarkable changes were observed. For example, blood glucose levels decreased by an average of 21%, insulin by 42%, and cholesterol by 30%. In addition, systolic blood pressure decreased by 25% and diastolic blood pressure by 22%. “We conclude that healthy nonobese humans on a low-calorie, nutrient-dense diet show physiologic, hematologic, hormonal, and biochemical changes resembling those of rodents and monkeys on such diets,” reported Dr. Walford and colleagues in their summary of the findings. “With regard to the health of humans on such a diet, we observed that despite the selective restriction in calories and marked weight loss, all crew members remained in excellent health and sustained a high level of physical and mental activity throughout the entire 2 years.”

While the findings of the Biosphere 2 study indicated beneficial effects for calorie restriction in humans, the two-year investigation was far from the type of decades-long longitudinal study needed to confirm the regimen’s effects on life span. Here we have a conundrum since, to accomplish this, one would need to design a study that would ideally involve life-long calorie restriction. The challenges of this type of study would be significant. Researchers conducting the investigation would need to be replaced as they retired or died. And how likely would it be that one could find human subjects willing to undergo a lifetime of restricted calories?

Larger and Long-Term Clinical Trials

Turns out, such a group already exists. CR Society International, founded by Roy Walford, Lisa Walford, and Brian Delaney in 1994, consists of several thousand men and women who practice calorie restriction in hope of retarding aging. As of this writing (2018), the group is still going strong. Research reported in the Proceedings of the National Academy of Sciences in 2004, conducted by gerontologist Luigi Fontana and colleagues, documented findings from 18 CR Society members who had practiced calorie restriction for six years.3 In addition to a leaner body mass and less body fat, the group had lower blood pressure, total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, fasting glucose, fasting insulin, C-reactive protein (CRP, a marker of inflammation) and other factors than a comparison group. Carotid artery intima media thickness, a measure of atherosclerosis, was approximately 40% less among those who practiced calorie restriction.

In the Comprehensive Assessment of Long term Effects of Reducing Intake of Energy (CALERIE) two-year clinical trial, the effects of a 25% reduction in calorie intake undertaken by 143 volunteers was compared to those experienced by 75 control subjects who were allowed to consume as much food as they wanted. In several analyses of the data, researchers (including Dr. Fontana) uncovered a number of benefits in association with calorie restriction, including a reduction in whole-body oxidative stress,4 and less whole-body and regional adiposity.5

“Accumulating data from observational and randomized clinical trials indicate that CR in humans results in some of the same metabolic and molecular adaptations that have been shown to improve health and retard the accumulation of molecular damage in animal models of longevity,” write Dr. Fontana and colleagues in a 2017 article titled “Calorie restriction in humans: An update.”6 “In particular, moderate CR in humans ameliorates multiple metabolic and hormonal factors that are implicated in the pathogenesis of type 2 diabetes, cardiovascular diseases, and cancer, the leading causes of morbidity, disability and mortality.”

Calorie Restriction Mimetics

For those who lack the willpower to restrict the amount of food consumed on a daily basis, calorie restriction mimetics—dietary compounds whose effects on gene expression mimic those of calorie restriction—may be a viable alternative. Compounds identified so far include resveratrol, pterostilbene, fisetin and grape seed extract.

The Bottom Line

Despite the challenges involved in assessing the benefits of calorie restriction in humans, researchers have persisted in their attempts to evaluate the regimen’s effects during the past couple of decades. Future research may find that CR practitioners are indeed biologically, if not chronologically, far younger than than those who consume much more food and calories and can look forward to many more years of good health and happiness.


  1. Cornaro L. Discourses on the Temperate Life. Benjamin White, London: 1779.
  2. Walford RL et al. J Gerontol Series A. 2002 June 1;57(6):B211-B224.
  3. Fontana L et al. Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6659-63.
  4. Il'yasova D et al. Aging Cell. 2018 Apr;17(2).
  5. Das SK et al. Am J Clin Nutr. 2017 Apr;105(4):913-927.
  6. Most J et al. Ageing Res Rev. 2017 Oct;39:36-45.

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