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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.
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.
8 Secrets to Biohacking Your Gut

8 Secrets to Biohacking Your Gut

There’s an old adage that while chiropractic doctors specialize in the spine, naturopathic doctors specialize in the gut. Working with what Dr. Henri Lindlahr, M.D., calls “nature’s laws” and grounded in the natural sciences, here are what I call 8 Secrets to Biohacking Your Gut, and they all involve the letter ‘P.’

1. Purification. Another name for purification is detoxification. There’s an old word for toxicity in the blood, toxemia, which according to Henri Lindlahr, M.D., one of the founders of naturopathic medicine, is caused by the violations of nature’s laws, and is equivalent with disease. (1) In this article, we may gloss over some of these laws, but if you want to learn more about them, check out The Naturopathic Medicine Institute.

Toxemia, aka accumulated “waste matter, morbid materials, and poisons,” must be removed by the organs of elimination, known as emunctories, lest their unchecked accumulation of toxicity lead to various manifestations of chronic disease. According to traditional naturopathic medicine, the five main emunctories are:

  • Liver
  • Gastrointestinal tract
  • Genitourinary tract
  • Lungs
  • Skin

According to traditional naturopathy, toxemia can be primarily reduced via sweat (skin), solid waste (intestines), liquid waste (kidney and urinary bladder), and gaseous waste (lungs). Interestingly, one feature these five emunctories share in common is ample epithelial tissue, which in part serves a defense function immunologically. (2) In the skin, epithelium connects via ducts to sweat glands, a type of exocrine gland which can remove pthalates, BPA, and even toxic metals from the body.

Biohack 1: Take a 40 minute infrared sauna, followed by a cold shower, at least once a week. An interesting aside: Did you know there’s a longitudinal study showing that there’s a significant association between sauna bathing and the reduction of cardiovascular disease and all-cause mortality. (3)

2. Pura Vida. This is the opposite of la vida loca, which induces stressWe know the expression of pura vida as the law of the land in Costa Rica, but at it’s core it really means living a pure life by reducing one’s exposure, as much as possible, to toxic substances, environments, and even thoughts. And yes, this means getting rid of processed sugar and industrial vegetable oils, because of the inflammatory byproducts they produce in our bodies. Because of epigenetics, as expounded upon by the likes of molecular biologist Bruce Lipton, we now know that we literally are what we eat, breathe, and think, and of course, as we follow food chains, we are what we eat ate, too.

Pura vida speaks for itself, but for illustrative purposes I’d like to briefly talk about the effects of stress on the gut. We have microvilli which comprise the brush border and extend into the lumen of our small intestine, responsible for nutrient absorption from our food breakdown. (4) Sloughed every seven days, these microvilli contain arteriovenous (AV) connections which provide necessary blood supply when closed, but in times of stress, the hormones epinephrine and norepinephrine open the AV connections and the microvilli lose their blood supply as blood is shunted away from the gut (think fight or flight). As a result, the microvilli cannot survive and lose their absorptive surface, temporarily inducing malabsorption. This is particularly pronounced after, for example, a severe stress-inducing trauma, such as a car accident, as it may take two or three days for the dead microvilli to slough and fully regenerate. It can be said then that chronic stress will induce chronic malabsorption and/or malnutrition.

We all know about “rest and digest,” which occurs when the parasympathetic nervous system is activated and we are not pumping out cortisol and adrenaline into our bloodstreams. It is just this relaxing state that we need to cultivate in order for pura vida to truly take hold in our lives, so that our digestion and nutrient absorption is optimized.

Biohack 2: When you’re feeling particularly toxic or maybe you’ve binged on that pizza and beer that you’d been craving, or maybe you’re traveling for business and can’t help but eat less nutrient-dense food along the way, keep some activated charcoal or digestive enzymes on hand.

3. Probiotics. 70% of our immune cells reside in the gut (5), and the highest density all-natural, bacterial ecosystem in the world is inhabited by our 100-trilliion celled gut microbiome. Our gut bacteria ferment fiber or collagen protein in the colon, producing short-chain fatty acids (SCFA), which are the main source of energy for superficial colonic cells. The most common (and famous) SCFA is butryic acid, which densely resides in grass-fed butter, such as Kerrygold.

Studies have shown that glucose tolerance is affected by our gut bacteria independent of weight. (6,7) And unhealthy bacteria can cause leaky gut, which has been linked to type 1 DM, IBD, celiac disease, MS, and even asthma; more common conditions linked to an unhealthy microbiome include acne, rosacea, stomachaches, headaches, and fatigue. (8,9,10)

It’s well established that allergies and asthma are illnesses most likely caused by diminished gut function and a compromised microbiome. (11) Oh, and your gut microbiota make vitamin B12 (12), an essential nutrient for making red blood cells, proper neurological function, and DNA synthesis. And 75% of your vitamin K is produced in the microbiome, which helps our blood clot and can keep us from bleeding excessively.

When talking dosage of commercial probiotics, the number of live organisms are known as “colony forming units,” or CFU’s. In most people, 5 to 10 billion viable CFU’s of L. acidophilus or B. bifidum cells daily will suffice. (Pizzorno, Textbook of Natural Medicine – 13)

Biohack 3: Take a probiotic daily, and eat fermented, probiotic-rich foods.

4. Prebiotics. Prebiotics are nondigestible food ingredients that help promote beneficial intestinal microbiomic growth, in particular fiber compounds. Like other high-fiber foods, prebiotic substances pass through the upper GI, remaining undigested until they arrive in the colon. Prebiotics are rich in foods such as garlic and onions, Jerusalem artichokes, jicama, chicory root, and even dandelion greens. In the colon, prebiotic compounds are fermented microbiomically.

The most famous type of fiber prebiotic are oligosaccharides, but when researchers refer to fiber, they also mean fructo-oligosaccharides, polysaccharides, and even inulin. Some carbs rich in prebiotics include sweet potatoes, carrots (I prefer the non-orange ones, which have a lower glycemic load, such as polyphenol purple! We’ll talk more about the power of purple soon!), squash, and asparagus. Then, there are also the resistant starches, so named because they are resistant to digestion, which further promote fermentation and help produce SCFAs like butyrate. Some resistant starches include banana flour, plaintain flour, and raw potato starch.

Biohack 4: Eat prebiotic-rich foods, such as those listed above.

5. Purple Polyphenols. Many plants contain naturally-occurring polyphenolic compounds: fruits, veggies, coffee, tea, and even

wine. But only about 10% of polyphenols are absorbed in the small intestine, while the rest end up in the colon to be degraded to metabolic byproducts by our gut bacteria (14). Research shows a symbiotic relationship between polyphenols and our gut microbiome, making a plant-rich diet even more important. (15) Polyphenols can even act prebiotically, to increase
Lactobacillus and Bifidobacteria. While dark leafy greens are perhaps the most polyphenolic, other polyphenol-rich foods include purple foods such as Concord grapes, black mission figs, prunes, plums, blueberries, and blackberries, as well as coffee and chocolate, and some spices. Oh, and polyphenols increase the presence of good bacteria such as Bacteroidetes, as opposed to the more so-called “bad” bacteria, such as Firmicutes. (16)

Biohack 5: Eat purple polyphenols, such as those listed above!

6. Proline and lysine. Did you know that in the lumen (inner part or tube) of your gut, the amino acids proline and lysine are hydroxylated (a fancy chemical word for the addition of an -OH group to a molecule), with the help of the cofactor Vitamin C, to make collagen?! (17) Pretty amazing, right? It means these nutrients are essential for gut tissue regeneration, which is occurring 24/7. Other nutrients required include L-glutamine and butyric acid.

Oh, and a couple of excellent demulcent herbs that aid in gut healing are slippery elm (Ulmus rubra), deglycyrrhizinated licorice (Glycyrrhiza glabra or DGL), and marshmallow root (Althaea officinalis). 

Another interesting tidbit: Vitamin C is a strong antioxidant, particularly in lowering antioxidant stress in the gut. (18) Apparently Eskimos got plenty of proline and lysine, as seal and whale contain high amounts, but we should probably hold off on eating them.

Biohack 6: Eat plenty of seaweed (an incredibly rich source of proline and lysine).

7. pH (or Proper Stomach Acid). It is essential that our gut is maintained within a highly acidic, proper pH range of 1.5 (fasting) to 3.5 (full stomach of food). Did you know that over 90% of our endogenous serotonin is made in our gut, indicating that “gut feelings” are no joke. (19) Actually, the serotonin made in the brain is a slightly different isomer than the serotonin made in the enteric nervous system, though serotonin influencing drugs, such as SSRI’s, can impact gut function as well. The gut-brain axis oversees everything from satiety, food intake, and glucose regulation, to insulin secretion and sensitivity, and bone metabolism. (20)

Biohack 7: Because studies have shown that stomach acid decreases with age, some natural means to stimulate the production of stomach acid, thereby improving fat breakdown and protein digestion, include betaine HCl and digestive bitters.

8. Purpose and the Solar Plexus. Okay, so here’s the woo-woo biohack. Did you know that according to the Tibetans, the solar

plexus chakra is where fire of the will in the individual is said to be localized? Interestingly, this is also where the fires of digestion roar. So, it can be said that being aligned with our life purpose will also optimize our gastrointestinal gusto. I know it’s kind of a stretch, for which there is no randomized controlled trial, but your gut’s stretch receptors will thank you. 🙂

Biohack 8: Deep belly breathing, regularly, on 4 to 8 counts at a time, can not only stimulate the will to action, but the fires of digestion.

Recapping 8 Gut Biohacks

So, to recount the 8 P’s for biohacking the gut: Purify, live Pura Vida, eat a probiotic-, prebiotic-, polyphenol-, and proline- and lysine-rich diet, maintain proper pH or stomach acid, and find and live your life purpose, thereby firing your solar plexus on all cylinders. And make it #naturopathic.

By the way, consult your doctor first if you are considering trying any of these therapies. In no way does this blog consist of medical advice.

Resources:
1. Lindlahr, Henry 1862-1924., “Nature cure: philosophy and practice based on the unity of disease and cure” (1922). Naturopathic Medicine Historical Collection.
2. Janeway C. Immunobiology: the immune system in health and disease. London: Harcourt Brace & Company; 1999.
3. Laukkanen T, Khan H, Zaccardi F, Laukkanen JA. Association Between Sauna Bathing and Fatal Cardiovascular and All-Cause Mortality EventsJAMA Internal Medicine. 2015;175(4):542.
4. Tortora GJ, Derrickson B. Principles of anatomy and physiology. New York: Wiley; 2006.
5. Vighi, G., Marcucci, F., Sensi, L., Di Cara, G. and Frati, F. (2008), Allergy and the gastrointestinal system. Clinical & Experimental Immunology, 153: 3–6.
6. Musso G, Gambino R, Cassader M. Obesity, Diabetes, and Gut Microbiota: The hygiene hypothesis expanded? Diabetes Care. 2010;33(10):2277-2284.
7. gshatyan L, Kashtanova D, Popenko A, et al. Gut microbiota and diet in patients with various glucose toleranceEndocrine Abstracts. 2016.
8. Campbell AW. Autoimmunity and the GutAutoimmune Diseases. 2014;2014:152428.
9. Gonzalez A, Hyde E, Sangwan N, Gilbert JA, Viirre E, Knight R. 2016. Migraines are correlated with higher levels of nitrate-, nitrite-, and nitric oxide-reducing oral microbes in the American Gut Project Cohort. mSystems 1(5):e00105-16.
10. Mosca A, Leclerc M and Hugot JP (2016) Gut Microbiota Diversity and Human Diseases: Should We Reintroduce Key Predators in Our Ecosystem? Front. Microbiol. 7:455.
11. Riiser A. The human microbiome, asthma, and allergyAllergy, Asthma, and Clinical Immunology : Official Journal of the Canadian Society of Allergy and Clinical Immunology. 2015;11:35.
12. Degnan PH, Taga ME, Goodman AL. Vitamin B12 as a modulator of gut microbial ecologyCell metabolism. 2014;20(5):769-778.
13. Pizzorno JE, Murray MT. Textbook of natural medicine. St. Louis, MO: Elsevier/Churchill Livingstone; 2013.
14. Tomás-Barberán F. Interaction of polyphenols with gut microbiota: Role in human healthPlanta Medica. 2014;80(16).
15. Duda-Chodak A, Tarko T, Satora P, Sroka P. Interaction of dietary compounds, especially polyphenols, with the intestinal microbiota: a reviewEuropean Journal of Nutrition. 2015;54(3):325-341.
16. Rastmanesh R. High polyphenol, low probiotic diet for weight loss because of intestinal microbiota interactionChemico-Biological Interactions. 2011;189(1-2):1-8.
17. Murad S, Grove D, Lindberg KA, Reynolds G, Sivarajah A, Pinnell SR. Regulation of collagen synthesis by ascorbic acidProceedings of the National Academy of Sciences of the United States of America. 1981;78(5):2879-2882.
18. Alzoghaibi MA. Concepts of oxidative stress and antioxidant defense in Crohn’s diseaseWorld Journal of Gastroenterology : WJG. 2013;19(39):6540-6547.
19. Yano JM, Yu K, Donaldson GP, et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesisCell. 2015;161(2):264-276.
20. Heijboer, A. C., Pijl, H., Van den Hoek, A. M., Havekes, L. M., Romijn, J. A. and Corssmit, E. P. M. (2006), Gut–Brain Axis: Regulation of Glucose Metabolism. Journal of Neuroendocrinology, 18: 883–894.

What do you think? I’d love to hear your thoughts!