COVID-19 and Some Evidence-Based Natural Medicine for Viral Respiratory Infections

COVID-19 and Some Evidence-Based Natural Medicine for Viral Respiratory Infections

This article takes a quick moment to review COVID-19, and some potential evidenced-based treatments to prevent or treat viral respiratory infections. However, just to be clear, there are no registered evidence-based treatments yet specifically for COVID-19.

The First Outbreak of COVID-19 and CT Findings

The first outbreak of COVID-19 (which stands for Coronavirus Disease 2019) occurred in December 2019 in Wuhan, Hubei Providence, China. Most infected patients were diagnosed with pneumonia and characteristic CT scans, therefore, CT findings are recommended as major evidence to detect early infection and for disease assessment. (1)Corona Virus COVID-19 evidence natural medicine treatment

Clinical Presentation of COVID-19

Clinical manifestations are nonspecific: runny nose, sore throat, cough, fever, and in severe cases, difficulty breathing. (2)

Transmission of COVID-19

Person-to-person transmission is thought mainly to occur much like that of influenza, that is, via respiratory droplets.

Typical CT Findings

Typical CT findings include ground-glass opacities (GGOs) which are peripherally distributed, with patchy consolidations. And posterior or lower lobe lung involvement is more common. If these GGOs are present in greater numbers or higher density, then it is indicative of disease progression. (3) The preferred type of CT is thin-slice, which is a slice thickness of 0.625 to 1.25 mm with a higher resolution, as opposed to the standard 5 mm CT imaging of the mediastinum and gross lungs. (4)

COVID-19 Viral Genome

Covid-19 virus infection natural medicineInterestingly, the viral genome of the COVID-19 shares 88% sequence identity with two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses.

Vitamin C and Viral Respiratory Infections

Because COVID-19 is a viral infection with proclivity to infect the respiratory tract, it stands to reason that vitamin C may help to prevent it.

A 1999 prospective, controlled study, from The Journal of Manipulative and Physiological Therapeutics, found that high dose vitamin C decreased the reported cold and flu symptoms of virus-induced respiratory infections by 85%. The treatment group received 1000 mg of vitamin C hourly, for the first six hours, and then three times daily thereafter. (5)

A 2017 review article in the journal, Nutrients, concluded that vitamin C plays a role in preventing and shorting diverse infections. In fact, five controlled trials found that vitamin C had significant benefit in treating pneumonia. (6)

Chinese Medicine and COVID-19

A 2020 guideline, in line with WHO standards, from the journal, Military Medical Research, details some Chinese medicine herbal protocols that might be used specifically for COVID-19 induced pneumonia: (7)

  • Moxa
  • Clove, fineleaf schizonepeta herb, Perilla frutescens, atractylodes lancea, cinnamon, biond magnolia flower, asarum sieboldii, and Elettaria cardamomum
  • Prescription of Chinese herbs for feet bath: vulgaris, carthamus, dried ginger
  • Chinese herbs for prophylaxis: Astragalus mongholicus, roasted rhizoma atractylodis macrocephalae, saposhnikovia divaricata, Cyrtomium fortunei, honeysuckle, dried tangerine or orange peel, eupatorium, and licorice

A 2020 Journal of Integrative Medicine in vitro study found 26 Chinese herbs, including licorice and gingko, used to treat viral respiratory infection with anti-COVID-19 properties. (8)

Vitamin D and Immunomodulation During Respiratory Virus Infection

Multiple studies have found that vitamin D has immunomodulatory properties that can improve the response to respiratory viruses. (9) A 2014 randomized controlled trial investigated vitamin D related respiratory disease in preschoolers, making the case that low wintertime vitamin D levels correlate with viral respiratory infections and asthma exacerbations in children. (10) Hence, bolstering up on vitamin D could lower the chances of a respiratory infection, such as COVID-19.

Selenium and Viral Infection

It’s a well known fact that selenium deficiency weakens our defense versus infectious disease agents by reducing selenoprotein expression. (11) As a key part of antioxidant defense, selenium helps to control oxidative stress, which can occur during viral respiratory infections. (12)

Zinc and Lower Respiratory Tract Infections

Zinc is a vital nutrient key to the growth and function of all cells in the human body.  According to the WHO, the fifth leading cause of mortality and morbidity in developing nations is zinc deficiency, estimated to affect one-third of the world population and accounting for 16% of lower respiratory tract infections. (13)

Summary

In summary, evidence points to vitamins C and D, zinc and selenium supplementation, and the use of Chinese herbal medicine, as possible evidence-based options for COVID-19 prevention and treatment. But it is recommended that these options are implemented only under the guidance of a board certified naturopathic doctor, or other integrative medicine physician. Also, just to reiterate, this article is not recommending treatments specifically for COVID-19, as there are as of yet no officially registered treatments back by evidence based studies.

Resources

  1. Zu ZY, Jiang MD, Xu PP, et al. Coronavirus Disease 2019 (COVID-19): A Perspective from ChinaRadiology. 2020:200490. doi:10.1148/radiol.2020200490.
  2. Raoult D, Zumla A, Locatelli F, Ippolito G, Kroemer G. Coronavirus infections: Epidemiological, clinical and immunological features and hypothesesCell Stress. 2020;4(4):66-75. doi:10.15698/cst2020.04.216.
  3. She J, Jiang J, Ye L, Hu L, Bai C, Song Y. 2019 novel coronavirus of pneumonia in Wuhan, China: emerging attack and management strategiesClinical and Translational Medicine. 2020;9(1). doi:10.1186/s40169-020-00271-z.
  4. Zu ZY, Jiang MD, Xu PP, et al. Coronavirus Disease 2019 (COVID-19): A Perspective from ChinaRadiology. 2020:200490. doi:10.1148/radiol.2020200490.
  5. Gorton H, Jarvis K. The effectiveness of vitamin C in preventing and relieving the symptoms of virus-induced respiratory infectionsJournal of Manipulative and Physiological Therapeutics. 1999;22(8):530-533. doi:10.1016/s0161-4754(99)70005-9.
  6. Hemilä H. Vitamin C and Infections. Nutrients. 2017;9(4):339. doi:10.3390/nu9040339.
  7. Jin Y-H, Cai L, Cheng Z-S, et al. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Military Medical Research. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003341/. Published February 6, 2020. 
  8. Zhang D-hai, Wu K-lun, Zhang X, Deng S-qiong, Peng B. In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus. Journal of Integrative Medicine. Published February 20, 2020. 
  9. Greiller CL, Martineau AR. Modulation of the immune response to respiratory viruses by vitamin D. Nutrients. Published May 29, 2015. 
  10. Maguire JL, Birken CS, Loeb MB, et al. DO IT Trial: vitamin D Outcomes and Interventions in Toddlers – a TARGet Kids! randomized controlled trial. BMC pediatrics. Published February 8, 2014.
  11. Guillin OM, Vindry C, Ohlmann T, Chavatte L. Selenium, Selenoproteins and Viral Infection. Nutrients. Published September 4, 2019. 
  12. Steinbrenner H, Al-Quraishy S, Dkhil MA, Wunderlich F, Sies H. Dietary selenium in adjuvant therapy of viral and bacterial infections. Advances in nutrition (Bethesda, Md.). Published January 15, 2015. .
  13. Gammoh NZ, Rink L. Zinc in Infection and Inflammation. Nutrients. Published June 17, 2017.
     
Can Mouthwash Cause Diabetes?

Can Mouthwash Cause Diabetes?

A 2017 study revealed that the use of mouthwash at least twice daily may be associated with a 50% greater likelihood of developing prediabetes/diabetes (1,2). Say what!? Is it possible that something as simple as swishing Listerine twice a day could double one’s chances of becoming diabetic?

Research into the so-called “salivary nitrate-nitrite-nitric oxide pathway” (3) has led to a growing body of evidence that there may be something to the proposed mechanism of action.

The Salivary Nitrate-Nitrite-Nitric Oxide Pathway

Interestingly, approximately 25% of the nitrate (the other 75% is excreted via the kidneys) that we absorb from our food (mostly from vegetables!) is uptaken by the salivary glands, where it becomes part of the saliva. (4)

This nitrate is then reduced by oral bacteria to nitrite, before it is swallowed and eventually converted to nitric oxide (NO). What is fascinating is that this nitrate helps these oral bacteria to produce energy via respiration in an anaerobic environment. (5)

The Role of Oral Bacteria in Nitric Oxide Production

Little research has been done on the oral microbiome. (6,7) The oral cavity is highly personalized, populated by bacteria strains of Streptococcus, Haemophilus (buccal mucosa), Actinomyces (supragingival plaque), Prevotella (subgingival plaque), and many more. (8)

Using a mouthwash that is “anti-bacterial” or “antiseptic” means that you’ll be indiscriminately laying waste to the good bacteria in your oral microbiome as you attempt to target the so-called bad guys, of which there are few. (9) Ironically, chronic gingivitis, dental caries, and even bad breath result from not having enough of the good guys.

Adding insult to injury, mouthwash is drying to the mouth, which disrupts saliva production. A little known fact is that saliva helps to remineralize the teeth, for example, using nutrient deposits such as phosphorous and magnesium. (10)

Putting The Mouth Back into the Body

The father of modern nutrition, Weston A. Price DDS, observed in his masterpiece, “Nutrition and Physical Degeneration,” that disease could be predicted by the state of oral health in the individual.

He, of course, traveled to many continents and observed dozens of natives in their original habitat, some of whom had not been affected, at least dietarily, by modern industrialized agriculture, which he found wreaked havoc on their oral health (and by extension, their overall health) when subsequently exposed

While disease begins in the gut, according to the father of modern medicine, Hippocrates, the gut does attach to the oral cavity. Perhaps the mouth can be considered to be an extension of the gut?

Nitric Oxide: Another Reason to Eat Your Veggies, Yo!

As a side note, some of the veggies richest in dietary nitrate are garlic and onions, eggplant and squash, arugula, beets, celery and rhubarb.

The Role of Nitric Oxide in Vascular Function

It is well established that nitric oxide (NO) plays an important role in vascular function in the body. (11) Nitric oxide is key to the function of our blood vessels, regulating vascular tone and blood flow, and inducing smooth muscle relaxation and vasodilation.

Without properly functioning blood vessels, hypertension and atherosclerosis are more a likely develop. Reduced levels of nitric oxide are also associated with insulin resistance. In fact, across the board diabetics have reduced levels of nitric oxide in their blood. (12)

What’s in Mouthwash?

If you love mouthwash, why not go with making your own, or at least buying all-natural mouthwash? Of course, it can be tricky figuring out exactly what “all-natural” means.

Mainstream mouthwash, for the most part, is full of artificial flavorings and colorings, with inferior essential oils, industrial chemicals (such as chlorine dioxide, an antibacterial bleaching agent), chlorhexidine (antibacterial and a common allergen) and even detergents such as sodium lauryl sulfate (common in toothpaste and to which many have a sensitivity).

Home-made DIY Mouthwash Recipe

  • Use small glass container, such as mason jar
  • 1.5 TBS baking soda
  • 1 cup distilled water
  • 2 drops tea tree essential oil
  • 2 drops ginger oil
  • 2 drops clove oil
  • 2 drops peppermint, wintergreen, or spearmint essential oil

Shake each time before using, as baking soda settles at bottom of container. Let one tablespoon swish in your mouth for 1-2 minutes. Avoid swallowing, especially when gargling.

Resources

  1. Joshipura KJ, Muñoz-Torres FJ, Morou-Bermudez E, Patel RP. Over-the-counter mouthwash use and risk of pre-diabetes/diabetesNitric Oxide. 2017;71:14-20. doi:10.1016/j.niox.2017.09.004.
  2. Preshaw PM. Mouthwash use and risk of diabetesBritish Dental Journal. 2018;225(10):923-926. doi:10.1038/sj.bdj.2018.1020.
  3. Hezel M, Weitzberg E. The oral microbiome and nitric oxide homoeostasisOral Diseases. 2013;21(1):7-16. doi:10.1111/odi.12157.
  4. Lidder S, Webb AJ. Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathwayBritish Journal of Clinical Pharmacology. 2013;75(3):677-696. doi:10.1111/j.1365-2125.2012.04420.x.
  5. Govoni M, Jansson EÅ, Weitzberg E, Lundberg JO. The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwashNitric Oxide. 2008;19(4):333-337. doi:10.1016/j.niox.2008.08.003.
  6. Gao L, Xu T, Huang G, Jiang S, Gu Y, Chen F. Oral microbiomes: more and more importance in oral cavity and whole bodyProtein & Cell. 2018;9(5):488-500. doi:10.1007/s13238-018-0548-1.
  7. Bars PL, Matamoros S, Montassier E, et al. The oral cavity microbiota: between health, oral disease, and cancers of the aerodigestive tractCanadian Journal of Microbiology. 2017;63(6):475-492. doi:10.1139/cjm-2016-0603.
  8. Aas JA, Paster BJ, Stokes LN, Olsen I, Dewhirst FE. Defining the Normal Bacterial Flora of the Oral CavityJournal of Clinical Microbiology. 2005;43(11):5721-5732. doi:10.1128/jcm.43.11.5721-5732.2005.
  9. Chino T, Santer DM, Giordano D, et al. Effects of oral commensal and pathogenic bacteria on human dendritic cellsOral Microbiology and Immunology. 2009;24(2):96-103. doi:10.1111/j.1399-302x.2008.00478.x.
  10. Neel EA, Aljabo A, Strange A, et al. Demineralization–remineralization dynamics in teeth and bone. International Journal of Nanomedicine. 2016;Volume 11:4743-4763. doi:10.2147/ijn.s107624.
  11. Loscalzo J, Jin. Vascular nitric oxide: formation and functionJournal of Blood Medicine. 2010:147. doi:10.2147/jbm.s7000.
  12. Tessari P, Cecchet D, Cosma A, et al. Nitric Oxide Synthesis Is Reduced in Subjects With Type 2 Diabetes and NephropathyDiabetes. 2010;59(9):2152-2159. doi:10.2337/db09-1772.
Three Foods for Natural Heavy Metal Chelation

Three Foods for Natural Heavy Metal Chelation

We are exposed to potential toxins, such as heavy metals, on a daily basis, no matter what we do. So why not also cook with foods that naturally help remove heavy metals from the body, a process known as chelation? This article briefly discusses heavy metal toxicity in seafood as well as three foods for natural heavy metal chelation, then combines it altogether in a recipe!

Heavy metal toxicity and fish
Seafood, and most prominently, fish, is not only an important source of protein, but also rich in essential minerals, vitamins, and unsaturated/essential fatty acids (EFAs). Yet it is just this nutrient-dense lipid content which can also pose the greatest harm.

Fish which contain the highest amounts of fat are potentially the most healthy (e.g., salmon, mackerel, herring, trout, sardines, and albacore tuna contain the highest amounts of EFAs). (1) But many of these same fish also can contain the highest heavy metal concentrations, specifically because heavy metals have an affinity for being sequestered in fat. Currently, some of the highest in methylmercury are king mackerel, marlin, orange roughy, shark, swordfish, tilefish, ahi tuna, and bigeye tuna. (2) In fact, it is recommended that women who are pregnant or trying to conceive avoid these types of fish. (3) Although the American Heart Association recommends eating fish at least twice a week to achieve recommended daily omega-3 fatty acid status, this can backfire if we aren’t careful about where we source our seafood, as well as which types we consume. (4)

The most famous heavy metal is mercury, which in its most harmful form is methylated. Methylation is a vital metabolic process which means that some carbon and hydrogen is attached to the mercury atom, making it more bioavailable to living organisms, such as fish swimming in the sea. Over time, then, this toxic methylmercury can concentrate in the fatty tissues of seafood via the ingestion of sediment, seawater, and oceanic food-chain organisms high in methylmercury. (5,6) One study found that fish muscles contained the least concentrations of heavy metals, while liver contained the highest amounts of copper, zinc, and iron, and gills contained the highest amounts of lead and manganese. (7)

Hence, it’s critical to eat sustainably harvested seafood, such as those provided by Vital Source Seafood, an inspiring company that only supplies sustainability certified fish and seafood (Marine Stewardship Council (MSC), State of Alaska, or Monterey Bay Aquarium SeafoodWatch program certified), such as wild-caught Alaskan salmon and northwest Pacific seafood, for a fair price and delivered flash-frozen to your doorstep.

Three foods that help your body remove heavy metals

1. Cilantro
The most famous herb for chelating heavy metals from the body is cilantro/coriander, or Coriandrum sativum, which has been specifically shown to help remove mercury, lead, and aluminum from the tissues. (8) Not only that, but it’s an immune-boosting herb.

2. Garlic and onions: Garlic, onion and shallot are sulfur rich foods which particularly help remove lead from the body. (9)

3. Brazil nuts: Brazil nuts contain high a

mounts of selenium, which has been shown to reduce metal toxicity. Selenium is critical for making the body’s most important antioxidant, glutathione, which protects from oxidative damage via an enzyme called gl

utathione peroxidase. (10) Selenium can actually actively bind methylmercury in the body, thereby rendering it less bioavailable and therefore less harmful. (11)

So why not cook sustainably harvested seafood with naturally chelating herbs, and feed two birds with one seed?! 🙂 I decided to sear a filet of wild-caught Alaskan Coho salmon with some of the ingredients mentioned above, and it came out wonderfully.

Recipe: Seared Coho Salmon with Cilantro and Brazil Nuts
¾ lb filet of wild-caught Alaskan Coho salmon
7 Brazil nuts, finely chopped
Cilantro, minced
1 shallot, minced
Coconut oil
Half a lemon
Freshly cracked pepper
Pinch of Maldon sea salt

Instructions
Heat cast-iron skillet on medium, adding 1 tbsp. of coconut oil in cast-iron skillet. Lightly sauté shallot for 3-4 minutes, then remove from pan. Heat pan until very hot, then add ½ tbsp. more of coconut oil. Sear salmon fillet on both sides for 2-3 minutes, until underside is lightly browned, ending with skin side down. Plate salmon, cover in sautéed shallot, sprinkle with Brazil nuts and cilantro. Add seasoning. Squeeze lemon over. Voila! 🙂

Resources:

  1. Fish and Omega-3 Fatty Acids. How Cigarettes Damage Your Body. http://www.heart.org/HEARTORG/HealthyLiving/HealthyEating/HealthyDietGoals/Fish-and-Omega-3-Fatty-Acids_UCM_303248_Article.jsp#.W1c9fthKg_U. Accessed July 24, 2018.
  2. Menon S. Mercury Guide. NRDC. https://www.nrdc.org/stories/mercury-guide. Published January 9, 2018. Accessed July 24, 2018.
  3. What You Need to Know about Mercury in Fish and Shellfish. WebMD. https://www.webmd.com/diet/mercury-in-fish#1. Accessed July 24, 2018.
  4. Kohlstadt I. Fish, mercury, and personalized medicine. Townsend Letter: The Examiner of Alternative Medicine. June 2007.
  5. How Does Mercury Get Into Fish? Scientific American. https://www.scientificamerican.com/article/how-does-mercury-get-into/. Accessed July 24, 2018.
  6. El-Moselhy KM, Othman A, El-Azem HA, El-Metwally M. Bioaccumulation of heavy metals in some tissues of fish in the Red Sea, EgyptEgyptian Journal of Basic and Applied Sciences. 2014;1(2):97-105. doi:10.1016/j.ejbas.2014.06.001.
  7. The Health Benefits of Cilantro. Dr. Group’s Healthy Living Articles. https://www.globalhealingcenter.com/natural-health/health-benefits-of-cilantro/. Published February 16, 2017. Accessed July 24, 2018.
  8. Negi, R., Satpathy, G., Tyagi, Y. K., & Gupta, R. K. (2012). Biosorption of heavy metals by utilising onion and garlic wastesInternational Journal of Environment and Pollution, 49(3/4), 179. doi:10.1504/ijep.2012.050898.
  9. Stockler-Pinto, M., Mafra, D., Farage, N., Boaventura, G., & Cozzolino, S. (2010). Effect of Brazil nut supplementation on the blood levels of selenium and glutathione peroxidase in hemodialysis patientsNutrition, 26(11-12), 1065-1069. doi:10.1016/j.nut.2009.08.006
  10. Ralston, N. V., & Raymond, L. J. (2010). Dietary selenium’s protective effects against methylmercury toxicityToxicology, 278(1), 112-123. doi:10.1016/j.tox.2010.06.004.

Zinc and The Metabolism of Alcohol

Zinc and The Metabolism of Alcohol

It’s well known that vitamin C, B complex vitamins, glutathione, and N-acetyl Cysteine (NAC) play a large role in alcohol metabolism, but zinc is rarely mentioned. However, zinc is actually a requisite cofactor in the metabolism of alcohol. (1) Zinc has not been studied extensively as a treatment for alcoholism, though alcoholics are usually zinc deficient and suffer from conditions which may benefit from zinc supplementation, such as low sperm counts and rosacea.

The body’s main enzyme for alcohol metabolism, alcohol dehydrogenase (ADH), actually contains zinc at its catalytic site. Zinc is now considered a novel therapeutic approach to alcohol liver disease (ALD). (2) ADH exists in decreased amounts in women, which contributes to less “first-pass metabolism,” and may in part explain why women are more susceptible to alcohol intoxication.

Zinc, an essential trace element, goes hand-in-hand with protein intake; in other words, poor protein intake correlates with poor zinc status. (3) Some symptoms of zinc deficiency include poor growth, infertility, skin disease, and impaired immune function.

The Epidemic of Chronic Alcoholism

Did you know that 50% of the world’s population drinks alcohol, and 5% to 10% have chronic alcoholism? In fact, over 3% of all deaths worldwide are due to alcohol. (4)

Ethanol

Ethanol is the natural product of sugar fermentation by yeasts. According to the USDA, one standard drink contains about half an ounce of ethanol. This is the equivalent of a light 12 oz beer, a 5 oz pour of wine, or 1.5 oz of an 80-proof distilled liquor. Ethanol is found in many household products, such as mouthwash, perfume, and cooking extracts.

The Metabolism of Alcohol

Alcohol is biotransformed to acetaldehyde by three main enzyme systems in the liver. (5)

  1. The first and main system lies in the cytosol of hepatocytes, where alcohol dehydrogenase (ADH) transforms ethanol to acetaldehyde. As mentioned, the ADHs are actually are actually a class of zinc enzymes!
  2. The second involves CYPs which oxidize ethanol in the microsomes of cells, known as the microsomal ethanol-oxidizing system (MEOS). Microsomes are basically fragments of hepatocellular endoplasmic reticulum.
  3. The third involves catalase in the peroxisomes, which acts upon hydrogen peroxide as substrate, metabolizing no more than 5% of all liver ethanol.

Ethanol crosses cell membranes, about 80% of its absorption occurring in the duodenum and 20% in the stomach itself. Peak blood ethanol levels are reached approximately 30 to 90 minutes after a meal. (6) Once ethanol reaches the blood, its taken up mainly by hepatocytes replete with ample quantities of ADH. ADH, however, is also available in the mucosa of the gut.

Zinc Status as a Biomarker of Chronic Alcoholism

Studies looking at evidence of the association of zinc metabolism and alcohol-associated disorders, such as those involving the liver, brain, lung, gut, and even fetal alcohol syndrome, suggest that zinc status should be used as a biomarker for alcohol abuse. (7,8) While it has been confirmed that alcohol induces autophagy in mice, a recent animal study found that adequate zinc intake is required for autophagy. (9)

Conclusion

Given that the body’s main enzyme system responsible for metabolizing alcohol in the liver is zinc-based, there appears to be enough evidence to warrant further studies in zinc supplementation for alcohol-induced diseases.

Resources

  1. Alcohol dehydrogenase. Egyptian Journal of Medical Human Genetics.
  2. Kharbanda K, Ronis M, Shearn C, et al. Role of Nutrition in Alcoholic Liver Disease: Summary of the Symposium at the ESBRA 2017 CongressBiomolecules. 2018;8(2):16. doi:10.3390/biom8020016.
  3. Gibson RS. A Historical Review of Progress in the Assessment of Dietary Zinc Intake as an Indicator of Population Zinc StatusAdvances in Nutrition. 2012;3(6):772-782. doi:10.3945/an.112.002287.
  4. Alcohol. World Health Organization. http://www.who.int/substance_abuse/facts/alcohol/en/. Published May 12, 2014. Accessed July 17, 2018.
  5. Alcohol Metabolism: An Update. National Institute on Alcohol Abuse and Alcoholism. https://pubs.niaaa.nih.gov/publications/aa72/aa72.htm. Accessed July 17, 2018.
  6. Mitchell MC, Teigen EL, Ramchandani VA. Absorption and Peak Blood Alcohol Concentration After Drinking Beer, Wine, or SpiritsAlcoholism: Clinical and Experimental Research. 2014;38(5):1200-1204. doi:10.1111/acer.12355.
  7. McClain CJ, Su LC. Zinc deficiency in the alcoholic: a review. Alcohol Clin Exp Res 1983;7:5-10.
  8. Skalny AV, Skalnaya MG, Grabeklis AR, Skalnaya AA, Tinkov AA. Zinc deficiency as a mediator of toxic effects of alcohol abuseEuropean Journal of Nutrition. 2017. doi:10.1007/s00394-017-1584-y.
  9. Liuzzi JP, Narayanan V, Doan H, Yoo C. Effect of zinc intake on hepatic autophagy during acute alcohol intoxicationBioMetals. 2018;31(2):217-232. doi:10.1007/s10534-018-0077-7.

How Cortisol Inhibits Active Thyroid Hormone and Suppresses Your Immune System

How Cortisol Inhibits Active Thyroid Hormone and Suppresses Your Immune System

Studies show that cortisol, your body’s stress hormone, increases thyroid-stimulating hormone (TSH), (1,2) as well as inhibits the conversion of T4 to T3, which is your body’s metabolically active thyroid hormone (3,4). This process mostly occurs peripherally in the liver, GI tract, skeletal muscle, but also occurs in the thyroid and even the brain itself. However, we need more studies verifying exactly how elevated cortisol levels mechanistically inhibits T4-to-T3 conversion.

Thyroid hormone acts to regulate metabolism by increasing basal metabolic rate, temperature, and heart rate/cardiac output. This, in part, explains why chronic stress can easily lead to hypothyroidism, because cortisol is literally turning off your metabolism. (5)

But why would cortisol inhibit T3 from being formed? Because T3 requires a lot of energy or ATP, to get stuff done in the body, and when the body is stressed, it needs to conserve energy so that it can act out of fight or flight.

Cortisol Is Increased by Stress and Hypoglycemia

There are two main stimuli (6) that lead to the release of cortisol from the zona fasciculata of your adrenal glands:

  1. Stress
  2. Hypoglycemia

What this basically means is that when your blood sugars are low, a stress response is mimicked in your body.

Relaxation (A Destressed State) and Hyperglycemia Inhibit Cortisol

So what inhibits cortisol? You guessed it:

  1. Not being stressed
  2. Hyperglycemia (having blood sugar that is too high)

Stress Can Be Physical or Psychological

Stress is a complex phenomenon which can be physical or psychological. Some examples of stressful events which are physical in nature include trauma, infection, or exercise. We already mentioned hypoglycemia. Psychological examples of stress include fear, bereavement, or anger.

Cortisol is Permissive

Did you know that cortisol is the only hormone in the body that has receptors on almost every cell. It must be pretty important then. And that’s why it goes everywhere, having no particular affinity for anything. There’s a word for this in science: Permissive. (7) When you’re superstressed, all of these cortisol receptors get upregulated, increasing cellular sensitivity. And there is no cellular second messenger, in case you were wondering. The message of cortisol is loud and direct.

The Role of Cortisol

But what does cortisol do in the body? Well, two things, mainly, physiologically:

  1. Proteolysis and Gluconeogenesis: Cortisol breaks down proteins, a process called proteolysis, so that the amino acids can be used to make glucose (gluconeogenesis). Remember, the body is in a state of hypoglycemia.
  2. Stress Lowers Your Immune System: Cortisol wields profound anti-inflammatory effect across the body. Cortisol destroys white blood cells, such as T-cells and eosinophils. Cortisol inhibits the migration of pathogen-engulfing, debris-cleaning macrophages. Cortisol stabilizes mast cells, who can be quite annoying when they unload histamine, as in Type 1 hypersensitivity reactions, such as seasonal allergies.

Cortisol also inhibits an enzyme called phospholipase, which is responsible for making prostaglandins by cleaving the phospholipid bilayer in the cell’s membranes and releasing arachidonic acid, which signals the body to make a host of important inflammatory molecules required by the immune system to do its job. (8) Remind you of the effects of steroids, by chance? Well, that’s because cortisol is an endogenous steroid.

Immunosuppression

Too much cortisol can lead to immunosuppression. (9) And when your immune system is down, that’s when you get sick. Ever get done with school finals for the term, only to be sick during your week off? Well, this is why.

When you experience a stressful event, such as an important exam, a romantic breakup, or a fender-bender, a cascade of hormones (10) are released in the engine of your body over approximately twenty-four hours.

The Cascade of Stress Hormones

  1. Epinephrine: First and immediately after the stressful event, epinephrine, aka adrenaline, is released. Epinephrine increases heart rate, raises blood sugar, and boost sugar metabolism.
  2. Glucagon: After about 20 minutes, glucagon is released from the alpha cells of the pancreas, causing blood sugar to be raised, as well as glycogen to be broken down (glycogenolysis), fats to be broken down (lipolysis), and ketones to be made (ketogenesis). Glucagon acts on the adrenal cortex, as well as the liver and adipose tissue.
  3. Cortisol: Within about 2 to 4 hours, cortisol is released.
  4. Growth Hormone: Then, after about 24 hours, growth hormone (GH) is released. This is one reason that high intensity interval trainings (HIIT), such as CrossFit, is effective for muscle growth, which doesn’t occur until one gets good sleep and after a couple days, because workouts are fast-paced and stressful. GH raises glucose levels and breaks down fat, releasing free fatty acids, produced by the anterior pituitary when we sleep. This is why a good night’s sleep is critical to get the benefits of HIIT.
  5. Insulin: Here’s one thing that’s a bit counterintuitive. Almost every metabolic process in the body is biphasic, balanced and counterbalanced by opposing regulatory feedback mechanisms. The hormones mentioned above will produce glucose in the body, which will increase the osmolarity of the blood. But after about 30 minutes, the body will release insulin, in order to push the excess glucose into the cells so that it can be used.
  6. Antidiuretic Hormone (ADH): After about 30 minutes, the body will also produce antidiuretic hormone (ADH), in order to normalize the blood osmolarity by retaining fluid volume rather than diuresing (a fancy word for urinating).
  7. Aldosterone: Cortisol works alongside the hormone aldosterone, as well, to increase sodium reabsorption in the kidneys, so that electrolyte and hydration status are appropriately maintained. As at least half of our blood is water, proper blood perfusion can occur in the body during fight or flight.

Conclusion

Cortisol, your body’s stress hormone, inhibits the conversion of T4 to T3, that is, your body’s metabolically active thyroid hormone.

If high cortisol levels are chronic, this can lead to hypothyroidism. Cortisol is the body’s endogenous corticosteroid, suppressing the immune system. Chronic stress can lead to frequently getting sick.

 

Resources:

  1. Walter KN, Corwin EJ, Ulbrecht J, et al. Elevated thyroid stimulating hormone is associated with elevated cortisol in healthy young men and womenThyroid Research. 2012;5(1):13. doi:10.1186/1756-6614-5-13.
  2. Hage MP, Azar ST. The Link between Thyroid Function and DepressionJournal of Thyroid Research. 2012;2012:1-8. doi:10.1155/2012/590648.
  3. Szivak TK, Lee EC, Saenz C, et al. Adrenal Stress and Physical Performance During Military Survival TrainingAerospace Medicine and Human Performance. 2018;89(2):99-107. doi:10.3357/amhp.4831.2018.
  4. Kahana L, Keidar S, Sheinfeld M, Palant A. Endogenous Cortisol And Thyroid Hormone Levels In Patients With Acute Myocardial InfarctionClinical Endocrinology. 1983;19(1):131-139. doi:10.1111/j.1365-2265.1983.tb00751.x.
  5. Ranabir S, Reetu K. Stress and hormonesIndian Journal of Endocrinology and Metabolism. 2011;15(1):18. doi:10.4103/2230-8210.77573.
  6. Gandhi K. Approach to hypoglycemia in infants and childrenTranslational Pediatrics. 2017;6(4):408-420. doi:10.21037/tp.2017.10.05.
  7. Mavroudis PD, Corbett SA, Calvano SE, Androulakis IP. Circadian characteristics of permissive and suppressive effects of cortisol and their role in homeostasis and the acute inflammatory responseMathematical Biosciences. 2015;260:54-64. doi:10.1016/j.mbs.2014.10.006.
  8. Goppelt-Struebe M, Wolter D, Resch K. Glucocorticoids inhibit prostaglandin synthesis not only at the level of phospholipase A2 but also at the level of cyclo-oxygenase/PGE isomerase. British Journal of Pharmacology. 1989;98(4):1287-1295. doi:10.1111/j.1476-5381.1989.tb12676.x.
  9. Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insightsMolecular and Cellular Endocrinology. 2011;335(1):2-13. doi:10.1016/j.mce.2010.04.005.
  10. Tsigos C, Kyrou I, Kassi E, et al. Stress, Endocrine Physiology and Pathophysiology. [Updated 2016 Mar 10]. In: De Groot LJ, Chrousos G, Dungan K, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK278995/

 

 

The Coffee Conundrum: A Proposed Life-Lengthening Mechanism

The Coffee Conundrum: A Proposed Life-Lengthening Mechanism

A growing body of research demonstrates an association between coffee drinking and a host of health benefits. Just this week, a new study showed premature death decreased by as much as 16% in those who consume 6 to 7 daily cups of coffee. (1) In 2017, the American Heart Association presented preliminary research showing a lowered risk of stroke and heart failure in coffee consumers (2), while decrease in risk of dementia, by as much as 65% in late age, has been well-established. (3,4)

Relying mainly on observational studies, there are many proposed mechanisms by which coffee may increase longevity and protect against cognitive decline, such as antioxidant capacity, increased insulin sensitivity, and the anti-inflammatory effects of blocking adenosine receptors in the brain. (5,6) This article will explore a potential mechanism which is little talked about, accounting for the gut-brain axis which links emotional and cognitive areas of the brain with intestinal functions.

Coffee Increases Gastric Acid (HCl) Secretion in the Gut

Coffee, both caffeinated and decaffeinated (7,8), increases the production of the hormone gastrin in the gut (9), the prime regulator of gastric acid (HCl) secretion. Specialized endocrine cells (G cells) release gastrin into circulation after a meal.

The G cells are tightly regulated by two hormones: gastrin releasing peptide (GRP), which exerts stimulatory effects in the gut and is countered by the inhibitory effects of somatostatin. The release of gastrin is controlled by a negative feedback loop whereby fasting and increased stomach acid will inhibit it and a high gastric pH will stimulate its secretion.

This may partially explain why long-term proton pump inhibitor (PPI) takers often have chronically elevated serum gastrin levels. PPIs inhibit the H+/K+-ATPase system found in gastric parietal cells, thereby suppressing gastrin levels, which will eventually cause the body to respond to stimulate the release of gastrin to maintain homeostasis.

The hormone gastrin increases stomach motility and gastric emptying. Nutrient absorption is only possible when stomach acid levels are at their proper levels. One study indicates that bitter taste signaling occurring in the gastric parietal cells plays a role in the release of gastrin. (10)

Coffee May Help Optimize Digestion and Nutrient Absorption, Especially as We Age

Low stomach acid (hypochlorhydria) is more common in the elderly (11). Is it possible that coffee’s life-lengthening health benefits are in part due to its effect on gastric parietal cells, helping to maintain optimal pH levels and a healthy microbiome, as well as optimize digestion and nutrient absorption. This may very well be the main reason that coffee consumption, no matter in what form, increases longevity. Unfortunately, more observational studies will not give us the answer.

 

  1. Loftfield E, Cornelis MC, Caporaso N, Yu K, Sinha R, Freedman N. Association of Coffee Drinking With Mortality by Genetic Variation in Caffeine MetabolismFindings From the UK BiobankJAMA Intern Med. Published online July 02, 2018. doi:10.1001/jamainternmed.2018.2425
  2. Drinking coffee may be associated with reduced risk of heart failure and stroke. Late-onset asthma linked to increased heart disease, stroke risk | American Heart Association. https://newsroom.heart.org/news/drinking-coffee-may-be-associated-with-reduced-risk-of-heart-failure-and-stroke. Accessed July 3, 2018.
  3. Santos C, Costa J, Santos J, Vaz-Carneiro A, Lunet N. Caffeine Intake and Dementia: Systematic Review and Meta-AnalysisJournal of Alzheimers Disease. 2010;20(s1). doi:10.3233/jad-2010-091387.
  4. Panza F, Solfrizzi V, Barulli MR, et al. Coffee, tea, and caffeine consumption and prevention of late-life cognitive decline and dementia: A systematic reviewThe journal of nutrition, health & aging. 2014;19(3):313-328. doi:10.1007/s12603-014-0563-8.
  5. Eskelinen MH, Kivipelto M. Caffeine as a Protective Factor in Dementia and Alzheimers DiseaseJournal of Alzheimers Disease. 2010;20(s1). doi:10.3233/jad-2010-1404.
  6. Chiu GS, Chatterjee D, Darmody PT, et al. Hypoxia/Reoxygenation Impairs Memory Formation via Adenosine-Dependent Activation of Caspase 1Journal of Neuroscience. 2012;32(40):13945-13955. doi:10.1523/jneurosci.0704-12.2012.
  7. Feldman EJ. Gastric Acid and Gastrin Response to Decaffeinated Coffee and a Peptone MealJAMA: The Journal of the American Medical Association. 1981;246(3):248. doi:10.1001/jama.1981.03320030040027.
  8. Deventer GV, Kamemoto E, Kuznicki JT, Heckert DC, Schulte MC. Lower esophageal sphincter pressure, acid secretion, and blood gastrin after coffee consumptionDigestive Diseases and Sciences. 1992;37(4):558-569. doi:10.1007/bf01307580.
  9. P. J. Boekema, M. Samsom, G. P. Van Be. Coffee and Gastrointestinal Function: Facts and Fiction: A ReviewScandinavian Journal of Gastroenterology. 1999;34(230):35-39. doi:10.1080/003655299750025525.
  10. Liszt KI, Ley JP, Lieder B, et al. Caffeine induces gastric acid secretion via bitter taste signaling in gastric parietal cellsProceedings of the National Academy of Sciences. 2017;114(30). doi:10.1073/pnas.1703728114.
  11. Russell RM. Gastric hypochlorhydria and achlorhydria in older adultsJAMA: The Journal of the American Medical Association. 1997;278(20):1659-1660. doi:10.1001/jama.278.20.1659.