Aloe vera is probably the most important medical food you should have for your healing.
Aloe vera has been considered a medical plant for thousands of years, thanks for its potential of remedying many of our common human ailments.
Did you know that 2000 years ago the Greek scientists regarded Aloe vera as a universal panacea? The Egyptians named the plant “the plant of immortality”.
Aloe vera has a long history of popular and traditional use such as for digestive issues, skin issues and infections, as well as high blood pressure and diabetes.
In Chinese medicine, it is often recommended to treat fungal diseases such as Candida.
Did you know that there is a total of 75 potentially active constituents that have been reported in the Aloe Vera plant? That includes things such as essential amino acids, vitamins, minerals, sterols, saponins among many more.
Aloe Vera provides 20 of the 22-human required amino acids, and 7 of the 8 essential amino acids.
It is also a good source of vitamin A, C, E, B1, B2, B3, B6, folate and choline. It contains many immune boosting minerals such as zinc, magnesium, copper, as well as calcium, manganese, chromium, selenium, potassium and sodium.
For those of you who have ran a hair tissue mineral analysis with me and found imbalances in your minerals, this is the perfect food.
In addition, some of these minerals are antioxidants and also support phase 1 and 2 liver detox pathways.
Mode of Action
The healing property of Aloe vera is associated with a compound called glucomannans, which is enriched with polysaccharides (such as mannose).
Aloe’s polysaccharides are known to have significant immunoregulatory and immunostimulatory activities. Aloe’s polysaccharides, particularly mannose-containing polysaccharides, cellulose, and pectic polysaccharides, comprise the major part of Aloe vera gel. Acetylated glucomannan is primarily responsible for the gel’s mucilaginous properties. Glucomannan has been found in vitro and in animal studies to modulate immune function (through macrophage activation and cytokine production) and accelerate wound healing The main effects include stimulation of phagocytosis, oxidative effects, and stimulation of humoral immunity (Foster et al, 2011)
The polysaccharides mend fibroblast growth factor and encourages the activity and proliferation of these cells result in more collagen and elastic fibers production. It also improves transversal connections among these bands making the skin more elastic and less wrinkled.
Mucopolysaccharides help in binding moisture into the skin and have anti-aging effect. There are some reports of aloe having an antitumor and antimicrobial effect as well but directly and indirectly. Direct effects are due to Anthraquinone which inactivate various enveloped viruses such as herpes simplex, influenza and varicella zoster. Indirect effect involves stimulation of the immune system _Kazina et al, 2017). Some components such as salicylic acid within aloe can promote anti-inflammatory and antibacterial properties. Other antiseptic agents include slupeol, salicylic acid, cinnamonic acid, phenols and sulfur that have an inhibitory action on bacteria, viruses and fungi. And some of the compounds present in aloe mucilage inhibit the production of reactive oxygen species and free radicals from human neutrophils.
ALOE VERA FOR DIGESTION AND BLADDER
But most importantly for IC Healers is the healing potential of aloe for digestive issues. As we know, there is a link to gut health and bladder health, as I explain in my IC Self Healing Course. In fact, a good % of people with bladder issues have leaky gut, and about 40% have small intestinal bacterial overgrowth (SIBO). Research has found that aloe vera gel was safe and effective of the “wound hormone” which was later identified as Acemannan. In fact, consuming aloe orally appeared to be the best route of administration for gut health.
Aloe vera contains a natural buffer system that can restore a healthy level of stomach acid by raising the pH enough to relieve discomfort of indigestion, but not enough to trigger the release of more acid. As a result, it appears to have a modulatory effect on digestion.
Aloe also functions as a prebiotic to promote the growth of good flora to optimize digestive function. Prebiotics promote the growth of beneficial bacterial populations such as Lactobacillus and Bifidobacterium species in the colon, accompanied by the production of short-chain fatty acids (SCFAs) through fermentation processes. These events have been associated with a lower risk of nontransmissible chronic diseases, including some types of cancer such as colorectal cancer. A recent study by Quezada et al (2017)
It has been shown that human intestinal flora metabolizes polysaccharides after ingestion of Aloe vera. There is some evidence that aloe vera by healthy individuals aids in the health of the bacterial flora which in turn results in improved health of the digestive system as a whole. This was evidenced by better protein digestion when tested from urine samples.
In addition, Aloe vera increases collagen content and degree of collagen cross linkage within the wound, therefore supporting faster wound healing
Stomach acid balancing, soothing of the gastrointestinal tract, promoting growth of good bacteria and delivery of the wound hormone Acemannan are some of the properties that have made Aloe vera the plant of choice for ages. Daily oral consumption of Aloe vera can eliminate dependence upon both types of drugs commonly used to control excessive hydrochloric acid without any of the negative side effects. To reduce potential contamination of the digestive tract from pathogens it is important to consume properly processed organic Aloe vera inner leaf gel powder from a reputable source.
More on Acemannan
As I said above, the nutraceutical properties of Aloe vera have been attributed to a glucomannan known as acemannan. Acemannan is a β(1,4)-acetylated mannan-based polysaccharide derived from the plant aloe vera (Barbadensis milleri). The reported range of biological effects of acemannan includes:
- stimulation of the production of IL-1a, TNF-a, IL-6, nitric oxide and prostaglandin E2 by macrophages
- enhanced macrophage phagocytosis
- antiviral activity
- induction of tumor cell apoptosis or necrosis
Acemannan strengthens and supports the immune system by activating the macrophages, antibodies, and the killer cells. It lowers the tendency of the body to develop allergies. Hence,
Acemannan possesses characteristics that stimulate the immune system, are antiviral, antibacterial, and antifungal. This means that Aloe Vera can prohibit Candida growth. In a study by Radha (2014), they indicated that aloe vera demonstrated antimicrobial activity against Candida paraprilosis, Candida krusei, and Candida albicans. In addition, A. vera has anthraquinones as an active compound, which is structural analogue of tetracycline. The anthraquinones acts like tetracycline that inhibits bacterial protein synthesis by blocking the ribosomal A site (where the aminoacylated tRNA enters)(Radha & Laxmipriya, 2015). Polysaccharides of A. vera gel have been attributed direct bacterial activity through the stimulation of phagocytic leucocytes to destroy bacteria. A. vera contains pyrocatechol a hydroxylated phenol, known to have toxic effect on microorganisms such as H. Pylori as well, a well known cause of gastric infection.
It is especially the Acemannan which appears to enforce the production of butyrate. Butyrate belongs to the short-chain fatty acids, which are of immense importance for the intestinal immune system.
OTHER BENEFITS OF ALOE
- Oral hygiene– A lesser known benefit of the Aloe Vera is that it helps fight gum disease. If you want a natural, chemical free solution to bleeding and tender gums, Aloe is a natural anti-inflammatory. This is especially important for those who have chronic UTI’s and embedded infections, as there are some links the Aloe has had positive results in treating ulcerative colitis.
Be warned, the taste leaves a lot to be desired. Many people have described the gel that comes from certain strains of the plant as bitter and nauseating, but the benefits outweigh the sacrifice of having the taste linger in your mouth for some time. If the taste is too much to bear, you also have the choice of using a sweetened Aloe Vera-based toothpaste.
2. Fasting, detox and weight loss- Aloe Vera has most recently been used in trendy juice cleanses and juice fast, and studies have shown that certain properties of the plant can promote weight loss. The detoxifying effect can clean out the colon and can also increase your metabolic rate. Bear in mind that healthy weight loss is only possible in conjunction with a healthy diet and a regular exercise schedule. You may also lose weight if you use Aloe Vera, as it will stop your body from retaining too much water, which causes bloating.
BEWARE OF IMPOSTER!
Despite clear beneficial effects of Aloe vera polysaccharides, some problems remain. There are virtually hundreds of different preparations on the market, vastly differing in types and quality of isolation, purity, and subsequently, their biological activities. Therefore, your aloe may not have any of the therapeutic and healing properties we mentioned.
Here are a few of the issues:
- Some commercial aloe products found in your health food store is NOT 100% aloe Vera, it is extremely filtered. The product manufacturers filtering the nutrients and antinutrients and bottling the water. That is why it doesn’t need preservatives and has an extremely long shelf life. That is also why it tastes like water. The water came out of the aloe plant. True aloe would have a very short shelf life.
- Most of your commercial aloe products does not have their own aloe firm. They are getting it from a 4th party as a powder. Often, it has been pasteurized prior to becoming a powder, which can ruin the properties of the aloe
- Pay attention when they dump in activated carbon and diamatecous earth to “purify it”. They push through a pressure filter to take it out. At the end they are testing the clear liquid. They are removing the color and odor which are the nutrients.
- Aloe vera gel often has added carrageenan that makes you think you are taking true aloe when in fact you are not.
I will be doing an interview with Dr. Haley, owner of Stockon aloe to discuss some of these and more. Stay tuned for the YouTube link below.
Here is a table that summarizes some of the many powers of aloe vera. It should be included in your healing regimen, provided that it is good quality as discussed. I strongly recommend the Stockton aloe as a medicinal food. I usually will purchase an 8-pack and freeze it to consume before my seasonal detox programs.
To order aloe, VISIT THIS LINK. I recommend you start with a 2 count first to see how you do, I am sure you will LOVE IT.
Amin K, Ozgen S, Selamoglu Z. Aloe Vera: a miracle plant with its wide-ranging applications. Pharm Pharmacol Int J. 2018;6(1):1-2. DOI: 10.15406/ppij.2018.06.00144
Foster M, Hunter D, Samman S. Evaluation of the Nutritional and Metabolic Effects of Aloe vera. In: Benzie IFF, Wachtel-Galor S, editors. Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition. Boca Raton (FL): CRC Press/Taylor & Francis; 2011. Chapter 3
Radha, M. H., & Laxmipriya, N. P. (2015). Evaluation of biological properties and clinical effectiveness of Aloe vera: A systematic review. J Tradit Complement Med, 5(1), 21-26. doi:10.1016/j.jtcme.2014.10.006
Vetvicka, (nd) Evaluation of immunological activities of an organic freeze dried inner leaf Aloe vera L powder
Powerful Phytochemical Rich Foods that Fight Cancer
Cancer is recognized worldwide to be a major health problem in the modern world. Cancer is a systemic disease with various causes, some of which include a poor diet, toxin exposure, nutrient deficiencies and to some extent genetics. The management of cancer can be invasive and complex, and involves conventional approaches such as surgery, radiation and chemotherapy. Despite these modern advances, cancer continues to account for fourteen million new cases and roughly eight million deaths each year (Kotecha, Takami, & Espinoza, 2016). As a result, alternative methods may be needed to improve the effectiveness of the treatments and quality of life of patients.
The good news is that certain foods are cancer fighting and can both prevent and also help in the treatment of cancer therapy! That is because foods contain phytochemicals. I like to think of them as fight-chemicals, or chemicals that help you fight disease. Phytochemicals are naturally occurring plant chemicals that play important roles in health (Murphy, Barraj, Spungen, Herman, & Randolph, 2014). For example, beta-carotene (think carrots) and lycopene (think tomatoes) can reduce the risk of cardiovascular disease (CVD). Others such as lutein and zeaxanthin may reduce the effects of oxidative damage that is associated with age related macular degeneration. And ellagic acid found in raspberries may reduce oxidative damage to DNA (Murphy et al., 2014).
Over production of free radicals and inflammation are some of the contributing factors to the development of cancer. Naturally occurring phytochemicals have been found to have a wide range of cellular effects that may be chemo-protective in the early stages of cancer. Antioxidant phytochemicals can be found in many foods and medicinal plants, and they play an important role in the prevention and treatment of chronic diseases such as cancer (Zhang et al., 2015). They can also enhance the immune system, improve elimination of cancerous cells and impact your body’s repair mechanisms aimed at suppressing tumors and inhibiting cellular growth (Kotecha et al., 2016).
Foods that prevent cancer
1. Turmeric (Curcumin)-Turmeric contains curcumin which is a polyphenol that gives turmeric its golden color and distinct aroma. Curcumin’s effects against cancer have only emerged in the last few decades (Park, Amin, Chen, & Shin, 2013). Curcumin is classified as an anti-proliferative, antioxidant and carcinogen blocking agent (Park et al., 2013). In an attempt to increase its bioavailability, several curcumin formulations have been developed such as powder, tablets, capsules, liposomal encapsulation, emulsions, and nanoparticles (Shanmugam et al., 2015). Curcumin is an excellent synergist and works well in combination with other compounds such as quercetin, bioperine, piperine, lactoferrin, and soy isoflavones (Shanmugam et al., 2015). Adding turmeric and black pepper to your onions would be a great anti-cancer synergistic side dish.
2. Blueberries-consist of anthocyanins (ACNs), a water -soluble flavonoid and a member of the flavonoid family. Anthocyanins offer rich, robust, deep, dark, and beautiful colors like blues, purples, and reds in many fruits, flowers and leaves (Fang, 2014). Anthocyanins are known for their antioxidant protection. They are also known for their anti-viral, anti-inflammatory, and anti-cancer benefits. This is accomplished by increasing scavenger hunting capabilities in cells which subsequently stimulates the Phase II detoxification system. In vitro animal studies demonstrated a reduction in oxidative stress as measured in urine (urinary 8- OHdG levels), indicating that berries may also reduce free radical-induced DNA damage in animals (Wang &Stoner, 2008).
3. Tomatoes-Tomatoes are high in a phytochemical called lycopene, which is actually a carotenoid that gives tomatoes their beautiful red color. Lycopene is one of the strongest antioxidant in nature and has both free radical scavenging properties as well as the ability to provide balance within the cell’s internal defense system (Gajowik & Dobrzynska, 2014). Epidemiological studies have shown that high intake of lycopene-containing vegetables is inversely associated with the incidence of certain types of cancer, including cancer of the digestive tract, prostate and cervix. Interestingly, a combination of vitamin E, selenium and lycopene has been shown to dramatically inhibit prostate cancer development and the increase disease free survival (Scarpa & Ninfali, 2015). A meal with tomatoes, brazil nuts and avocados may be a great way to prevent prostate cancer. Lycopene has also been shown to inhibit cell proliferation and is able to induce programmed cell death of cancer cells (Kotecha et al., 2016). Tip: dietary fats can enhance lycopene absorption and metabolism. Go ahead and add some olive oil to your tomato sauce to enhance the cancer-fighting properties of lycopene.
4. Sweet potatoes- Sweet potatoes contain beta-carotene which gives them their nice orange color. The human body converts beta-carotene into vitamin A (retinol) making beta-carotene a precursor to vitamin A, which is an essential nutrient. Beta-carotene, like lycopene, exhibits anti-oxidant properties that can protect the body from free radicals, a primary cause of aging, degeneration and cancer. Beta-carotene has also been identified in the ability to inhibit the growth of cancer stem cells in neuroblastoma (Scarpa & Ninfali, 2015). The only caveat is taking beta-carotene if you are a smoker. Studies indicate that smokers can actually have an increased risk of cancer if supplemented with beta-carotene. (Virtamo et al., 2014). These findings indicate that if you smoke heavily you should consult with your health care provider before supplementing with beta-carotene.
Foods that can treat cancer
1. Aloe Vera– Aloe Vera is an amazing mixture of more than 200 constituents, including polysaccharides, enzymes, glycoproteins, amino acids, vitamins and minerals. Aloe Vera contains polysaccharides that has been associated with immune modulation (Foster, Hunter, & Samman, 2011). These polysaccharides have been shown to act as a bridge between foreign proteins and immune cells (macrophages) in the human body, facilitating the destruction of the foreigner by the macrophage. One polysaccharide in particular is called acemannan, which can interject itself into all cell membranes which can improve the metabolism of the cell. Also, acemannan is known to have antiviral and antitumor activities through activation of immune responses. Acemannan induces your macrophages to secrete three anti-cancer compounds: interferon, tumor necrosis factor-α, and interleukins. Other immune functions of acemannan include: reducing inflammation, improve macrophage function, enhance antibody release, increase T-cell production, and improve nutrient absorption through the GI-tract.
2. Green tea catechins-Green tea is a flavanol polyphenol that is really a fancy word for antioxidant compounds in the food. Of all the antioxidant compounds found in green tea, the major constituents are the polyphenols, including phenolic acids and catechins (Du et al., 2012). ECGC is the major catechin in green tea that is known for its robust antioxidant activity. In fact, effects of green tea on chemoprevention have been attributed to its antioxidant potential. They can act on inflammatory processes by altering the recruitment of inflammatory cells from the circulation (Tangney & Rasmussen, 2013). Polyphenols in green tea can improve oxidative stress markers. Green tea’s ECGC is thought to exert their anti-oxidant power by preventing specific DNA damage by free radicals and preventing tumor formation (Kotecha et al., 2016) Green tea polyphenols have been shown to directly inhibit tumor cell growth by inducing apoptosis (programmed cell death) through multiple pathways linked in cancer development.
Hippocrates once said, “let food be thy medicine, and medicine be thy food”. One of the best ways to prevent cancer is through the diet. Check out my recipes to find some cancer fighting recipes that you can enjoy!
Du, G. J., Zhang, Z., Wen, X. D., Yu, C., Calway, T., Yuan, C. S., & Wang, C. Z. (2012). Epigallocatechin Gallate (EGCG) is the most effective cancer chemopreventive polyphenol in green tea. Nutrients, 4(11), 1679-1691. doi:10.3390/nu4111679
Foster, M., Hunter, D., & Samman, S. (2011). Evaluation of the Nutritional and Metabolic Effects of Aloe vera. In nd, I. F. F. Benzie, & S. Wachtel-Galor (Eds.), Herbal Medicine: Biomolecular and Clinical Aspects. Boca Raton (FL): CRC Press/Taylor & Francis
Gajowik, A., & Dobrzynska, M. M. (2014). Lycopene – antioxidant with radioprotective and anticancer properties. A review. Rocz Panstw Zakl Hig, 65(4), 263-271.
Kotecha, R., Takami, A., & Espinoza, J. L. (2016). Dietary phytochemicals and cancer chemoprevention: a review of the clinical evidence. Oncotarget, 7(32), 52517-52529. doi:10.18632/oncotarget.9593
Murphy, M. M., Barraj, L. M., Spungen, J. H., Herman, D. R., & Randolph, R. K. (2014). Global assessment of select phytonutrient intakes by level of fruit and vegetable consumption. Br J Nutr, 112(6), 1004-1018. doi:10.1017/s0007114514001937
Park, W., Amin, A. R., Chen, Z. G., & Shin, D. M. (2013). New perspectives of curcumin in cancer prevention. Cancer Prev Res (Phila), 6(5), 387-400. doi:10.1158/1940-6207.capr-12-0410
Scarpa, E. S., & Ninfali, P. (2015). Phytochemicals as Innovative Therapeutic Tools against Cancer Stem Cells. Int J Mol Sci, 16(7), 15727-15742. doi:10.3390/ijms160715727
Shanmugam, M. K., Rane, G., Kanchi, M. M., Arfuso, F., Chinnathambi, A., Zayed, M. E., . . . Sethi, G. (2015). The multifaceted role of curcumin in cancer prevention and treatment. Molecules, 20(2), 2728-2769. doi:10.3390/molecules20022728
Tangney, C. C., & Rasmussen, H. E. (2013). Polyphenols, inflammation, and cardiovascular disease. Curr Atheroscler Rep, 15(5), 324. doi:10.1007/s11883-013-0324-x
Virtamo, J., Taylor, P. R., Kontto, J., Mannisto, S., Utriainen, M., Weinstein, S. J., . . . Albanes, D. (2014). Effects of alpha-tocopherol and beta-carotene supplementation on cancer incidence and mortality: 18-year postintervention follow-up of the Alpha-tocopherol, Beta-carotene Cancer Prevention Study. Int J Cancer, 135(1), 178-185. doi:10.1002/ijc.28641
Zhang, Y. J., Gan, R. Y., Li, S., Zhou, Y., Li, A. N., Xu, D. P., & Li, H. B. (2015). Antioxidant Phytochemicals for the Prevention and Treatment of Chronic Diseases. Molecules, 20(12), 21138-21156. doi:10.3390/molecules201219753
I recently stumbled upon Maitake mushrooms as I have been searching for methods to increase my own immune system. For thousands of years mushrooms have been highly respected in Asia for their health promoting properties. Maitake (Grifola frondosa) is called the “King of Mushrooms” and it known for its immune enhancing compounds with significant anticancer effects. Modern research on maitake began in the early late 1970s in Japan under the direction of Dr. Hiroaki Nanba. He was researching the immune enhancing properties of mushrooms when he came to the conclusion that maitake extracts demonstrated more pronounced antitumor activity in animal tests than other mushroom extracts. In 1984, Dr. Nanba identified a fraction of maitake that possessed a significant ability to stimulate macrophages. Throughout the late 1980s and into the 1990s, Dr. Nanba and other Japanese researchers continued to study maitake, trying to improve upon the antitumor and immune potentiating activity of maitake. The result of their work was the development and patent of MaitakeGold.
How does Maitake work?
Maitake polysaccharides contain a unique beta-1,6 1,3 glucan structure. Beta-glucans are naturally occurring polysaccharides with distinctive beta 1,3 linked and beta 1,6 linked glucose polymers that are expressed by fungi, plants including cereals, grains, mushrooms, and some bacteria (Lin et al., 2010). “Beta-glucans are not expressed on mammalian cells and are recognized as pathogen-associated molecular patterns (PAMPS) by several types of pattern recognition receptors” (Lin et al., 2010). For leukocytes, the primary receptor for beta-glucan is the C-type receptor dectin-1, which can trigger phagocytosis, production of cytokines and chemokines, and activation of effector cell functions according to the cell type and specific properties of the beta-glucan compound.
Maitake exerts profound effects on immune function through mechanisms via the beta-glucan components. An extract of these helpful glucans was patented and is known as the maitake D-fraction, which has been shown to have anti-tumor activity while enhancing cytotoxic activity of macrophages and elevated production of IL-1. Unlike many other mushroom extracts that have to be injected intravenously, Maitake D-fraction has a strong ability to inhibit tumor growth when given orally as well (Superfoods, n.d.). Beta-glucans, like those in maitake, can also protect against myelotoxic injury (bone marrow suppression) following radiation and chemotherapy (Lin et al., 2010).
Maitake can increase the ability of the macrophages to engulf and destroy cancer cells, microbes, and other foreign cells, the binding stimulates the production of important signaling proteins of the immune system such as interleukin-1 interleukin-2, and lymphokines. These immune activators stimulate defenses by activating immune cells.
The beta-glucan components can bind to receptors on outer membranes of macrophages and other white blood cells such as natural killer (NK) cells and cytoxic T-cells, which can attack tumors directly. “Just like a key in a lock, the binding of the maitake components literally flips white blood cells on and triggers a chain reaction leading to increased immune activity”(Murray, 2014). Maitake also stimulates the production of white blood cells within the bone marrow. Reduced bone marrow production means lowered white cell counts and an increased risk of infection and cancer. This beneficial effect of the beta-glucan can be helpful for cancer patients undergoing radiation therapy or chemotherapy.
Researchers at Memorial Sloan-Kettering Cancer Center conducted a study in patients suffering from Myelodysplastic Syndrome (MDS) – a bone marrow disorder in which the bone marrow does not produce enough healthy blood cells. MDS patients received oral maitake extract at 3 mg per kg body weight twice daily for 12 weeks. Results indicated that maitake increased the function of neutrophil and monocyte white blood cells. The researchers also demonstrated that white blood cell response to E. coli bacteria is reduced in MDS patients but could be restored after 12 weeks of Maitake treatment. They also demonstrated that the ability of monocyte and neutrophils to destroy and digest infecting organisms. The proposed mechanism includes the ability of maitake treatment to stimulate the maturation of these immune cells in the bone marrow, leading to the release of more functionally competent cells.
Dosing of Maitake
Typically, the daily dosage range of maitake extract based upon body weight has been 0.5mg to 1.0 mg for every kg of body weight per day. That translates to a dosage of approximately 68mg per day for 150lb person. (This study used a dosage of 3 mg/kg to show an immediate clinical effect.) For best results take 20 minutes before meals or on an empty stomach.
Here are a few products that utilize Maitake. Glycolife is owned by my friend and FDN colleague whom I trust his quality very much.
Buy Maitake here, use coupon ICHealer for discount
Lin, H., de Stanchina, E., Zhou, X. K., Hong, F., Seidman, A., Fornier, M., . . . Cunningham-Rundles, S. (2010). Maitake beta-glucan promotes recovery of leukocytes and myeloid cell function in peripheral blood from paclitaxel hematotoxicity. Cancer Immunol Immunother, 59(6), 885-897. doi:10.1007/s00262-009-0815-3
Murray, M. (2014). Maitake Extract Produces Beneficial Effects on the Immune System in Patients with Bone Marrow Failure. Retrieved (2018, July 9) from http://doctormurray.com/maitake-extract-produces-beneficial-effects-on-the-immune-system-in-patients-with-bone-marrow-failure/
Superfoods. (n.d.) Maitake Benefits and Cancer Research. Retrieved (2018, July 9) from http://www.superfoods-scientific-research.com/superfoods/maitake-benefits.html
I don’t recommend high consumptions of coconut oil and saturated fats such as often found in ketogenic diet and here is why. Both gram positive and gram negative bacteria are present in large quantities in the intestine. Gram negative bacteria, such as E. coli, might be one of the major sources for circulating endotoxin. “It has been estimated that a single cell of Escherichia coli contains approximately 106 Lipid A or endotoxin molecules and a typical human intestinal tract could harbor approximately one gram of endotoxin” (Mani, Hollis, & Gabler, 2013) The endotoxin is the gram negative bacterial outer cell wall also known as lipopolysaccharide (LPS). Even in small quantities, LPS has the potential to elicit and inflammatory response systemically. Endotoxins are thought to enter circulation through leaky intestinal epithelium in the context of leaky gut.
In recent years accumulating research has investigated the link between dietary fat and endogenous endotoxin in relation to metabolic inflammation. Current evidence suggests that dietary fat can increase circulating endotoxin concentrations. The resulting postprandial endotoxemia leads to low-grade systemic inflammation which has been implicated in the development of several metabolic diseases such as atherosclerosis, obesity, type 2 diabetes and Alzheimer’s disease (Mani et al., 2013). It has been theorized that different types of dietary oils can differentially alter intestinal endotoxin transport. According to a few studies I read, oils rich in DHA and EPA (fish oil, cod liver oil, algae oil) can attenuate LPS transport, while oils higher in saturated fats (coconut oil, palm oil, animal fats) can increase transport.
Interestingly, canola oil and sunflower oil, although containing a high unsaturated fatty acid content, augmented plasma endoxemia by 50-75%. A majority of these studies show that consuming high saturated fat diet for a longer period results in higher gram negative bacterial populations and high fiber diets results in gram positive bacterial populations. “Furthermore, even though the mechanism is not clear, high intake of fat has been shown to cause internalization of tight junction proteins and increase in the paracellular permeability to macro molecules including endotoxin” (Mani et al., 2013). Better to increase your consumption of polyunsaturated fats such as fish oil and monounsaturated fats such olive oil. This is another reason why I do not recommend long term ketogenic diets, particularly due to the high saturated fat intake.
Mani, V., Hollis, J. H., & Gabler, N. K. (2013). Dietary oil composition differentially modulates intestinal endotoxin transport and postprandial endotoxemia. Nutr Metab (Lond), 10(1), 6. doi:10.1186/1743-7075-10-6
Mani, V. (2012) Understanding intestinal lipopolysaccharide permeability and associated inflammation. Retreived (2018, July 18) from https://lib.dr.iastate.edu/etd/12788/
I often recommend quercetin to my clients that I educate on supplements that are beneficial for modulating inflammation. During my research on the benefits of quercetin, I found some interesting literature that seems promising in the therapy of bladder conditions. UTI’s are one of the most common bacterial infections of the bladder and account for almost 95% of all the visits to physicians for UTI’s (Wang et al., 2012). Patients with acute cystitis always have symptoms of dysuria and increased frequency and urgency of urination. As I have already experienced, this can seriously affect a person’s quality of life. The incidence of acute cystitis is high, and the course of acute cystitis is urgent. If acute cystitis cannot be treated promptly, it will be transformed into chronic cystitis. “It can also be transformed into cystitis glandularis, and finally into bladder cancer. It can also induce nephritis. Therefore, timely treatment of acute cystitis is necessary” (Wang et al., 2012).
Currently, acute cystitis is commonly treated by systemic application of antibiotics and anti-inflammation agents. However, only a small amount of systemically administered drugs can reach the bladder. In recent years, the anti-inflammatory effect of querctin (QU) has been well recognized, demonstrating promising clinical application. Recently, it was found that QU can be used to prevent interstitial cystitis (Wang et al., 2012). There are many quercetin containing supplements available in the market, and some of them specifically aimed to treat the bladder. One of them, Cystoprotek, contains QU and rutin with the aims of reducing bladder wall inflammation (Theoharides, Kempuraj, Vakali, & Sant, 2008). Unfortunately it was recently pulled off the market. An older product, Cysta-Q, was shown to provide symptomatic improvements in patients with IC (Katske et al., 2001). Personally, neither of these supplements did anything significant for my IC symptoms at the time I was taking them. This could be due to the inability of the active ingredients to reach the bladder.
Another product that seems promising is Perque Repair Guard. The antioxidant value is of 12 servings of fruits and vegetables. It has 1g of quercetin per tablet. And other healing ingredients such as pomegranate juice powder, OPC, magnesium, chlorophyll, turmeric, and vegetable fiber.
Interestingly, some clinicians are exploring intravesical administration. This means directly instilling the drug solution into the bladder through a urethral catheter, ensuring maximum delivery of active ingredients to the bladder (Wang et al., 2012). According to Wang et. al, the bladder is an idea organ for regional therapy because it urethra provides easy access of the therapeutic agent to the bladder (Wang et al., 2012). In addition, intravesical drug administration has other potential benefits such as avoiding the first-pass metabolism, increasing drug utilization and reducing system toxicity and side effects (Wang et al., 2012). The study conducted by Wang et. al involved encapsulating nanoparticles of water soluble QU into micelles to ensure proper absorption. The results of this study found that intravesical application of the micelles did not induce any toxicity to the bladder. Even better, intravesical administration of QU micelles efficiently reduced the inflammation of the bladder with E. coli-induced acute cystitis. Results indicated that the quercetin micelle treatment can efficiently reduce the edema and inflammatory cell infiltration of the bladder in an E. coli-induced acute cystitis model (Wang et al., 2012). The data from this study proved the hypothesis that QU had potential application in acute cystitis therapy. I am looking forward to seeing future studies in the application, as there are millions of men, women, and even children suffering from this very debilitating condition!
Katske, F., Shoskes, D. A., Sender, M., Poliakin, R., Gagliano, K., & Rajfer, J. (2001). Treatment of interstitial cystitis with a quercetin supplement. Tech Urol, 7(1), 44-46.
Theoharides, T. C., Kempuraj, D., Vakali, S., & Sant, G. R. (2008). Treatment of refractory interstitial cystitis/painful bladder syndrome with CystoProtek–an oral multi-agent natural supplement. Can J Urol, 15(6), 4410-4414.
Wang, B. L., Gao, X., Men, K., Qiu, J., Yang, B., Gou, M. L., . . . Wei, Y. Q. (2012). Treating acute cystitis with biodegradable micelle-encapsulated quercetin. Int J Nanomedicine, 7, 2239-2247. doi:10.2147/ijn.s29416
Water fasting for reversing Interstitial Cystitis (IC) symptoms? Say it isn’t so! As one study suggests: “In rodents, intermittent or periodic fasting protects against diabetes, cancers, heart disease and neurodegeneration, while in humans it helps reduce obesity, hypertension, asthma and rheumatoid arthritis.”
Can it help overcome the pain associated with IC and is it right for you? Fasting seems to be the latest health trend, with intermittent fasting, alternate-day fasting, and water fasts are becoming quickly popular in the wellness arena. Water fasts have been used for centuries and have been done in a number of different ways and for varying lengths of time, usually five to 40 days.
What is a water fast?
In a true water fast, you are limited to drinking only water and no food for the duration of the fast. Interestingly, modern science has found a variety of verifiable positive effects of fasting that has on human health. However, there are some downsides to fasting as well, so it is important to review both the positive and negative to determine if fasting is right for you.
Benefits of Water Fasting for IC
- Autophagy. My number one favorite benefit is the process of autophagy. The term ‘autophagy’, derived from the Greek meaning ‘eating of self’, was first coined by Christian de Duve over 40 years ago (Glick, Barth, & Macleod, 2010). Autophagy is your body’s normal, natural process for recycling unnecessary or dysfunctional components. The body reprograms itself, clearing out old cells or damaged cells and replacing them with new ones (Cheng et al., 2014). This means that fasting can encourage your body’s natural healing mechanisms to actively destroy and recycle damaged tissues, which may have a positive effect on several serious conditions. This can often lead to improved immunity and reduction in autoimmune symptoms. The idea is the body gets rid of damaged autoimmune cells and replaces them with healthy new ones. This could come handy since IC is characterized by recurrent inflammation and destruction of bladder tissue without obvious cause, that some speculate could be a broken immune system response.
- Improved digestive health. Research suggests that fasting can improve digestive health, allowing good bacteria to flourish, resulting in an overall improvement in metabolism, weight, and many other cardiometabolic conditions. Fasting is also a great break for your gut, which is often helpful if you have food intolerances and allergies. The elimination of food antigens can also reduce inflammation that is often associated with chronic pain and immune dysfunction. This is because water fasting can upregulate a T cell response, called T-regulatory cells, that are involved in oral tolerance of food. In fact, eating foods that your body is intolerant to can make your immune system work too hard and make your more susceptible to infections. Therefore, giving your gut a break can actually enhance immunity and reduce inflammation, a crucial symptom of IC. (Make sure you follow up the fast with a healthy diet and probiotics)
- Improved markers of metabolic syndrome. Water fasting can improve aspects of metabolic syndrome: abdominal fat, inflammation and blood pressure are reduced. Insulin sensitivity is increased, and the functional capacities of the nervous, neuromuscular and cardiovascular systems are improved (Longo & Panda, 2016). Fasting results in a lowering of the hormones insulin and leptin levels and an elevation of adiponectin and ghrelin levels. By increasing insulin and leptin sensitivity, you can suppress inflammation and stimulate autophagy. Fasting can reverse all the major abnormalities of metabolic syndrome such as reduced body fat, blood pressure and glucose metabolism (Longo & Mattson, 2014).
- Slowed aging. There are biomarkers that are associated with reduced aging when you water fast. These include changes in the levels of signals in your body, such as IGF-1, IGFBP1, glucose, and insulin. Fasting for 3 or more days causes a 30% or more decrease in circulating insulin and glucose, as well as rapid decline in the levels of insulin-like growth factor 1 (IGF-1), the major growth factor in mammals. Together with insulin, reducing growth factor is associated with decreased aging and cancer (Longo & Mattson, 2014). It could also slow down the aging of your immune system so that you are less susceptible to infections.
- Reduction in oxidative stress. Oxidative stress is a condition where too much oxygen can wreak havoc in your cells. It’s complicated, but the bottom line is that oxidative stress is an indication that you are out of balance on a cellular level. This condition can cause excessive fatigue, brain fog, muscle and joint pain, wrinkles, gray hair, poor eyesight, headaches and sensitivity to noise, and a decreased immune system. And a decreased immune system makes you more at risk of getting even more infections.
Risks of Water Fasting
- Dehydration. Although it sounds strange, a water fast could make you dehydrated. This is because roughly 20 to 30% of your daily water intake comes from the foods you eat. Symptoms of dehydration include dizziness, nausea, headaches, constipation, low blood pressure and low productivity. To avoid dehydration, you will need to drink a lot more water than you are used to drinking.
- Loss of electrolytes. During a water fast, you may lose electrolytes, which are needed for your heart to function. This can lead to abnormal heartbeats and can potentially be dangerous in susceptible individuals. Drink electrolyte water to prevent this from occurring if you decide to water fast.
- Low blood sugar. Some people have reactive hypoglycemia and may find it difficult to fast. This is because they are not efficient at using fat for energy, and may struggle to transition to ketosis. What is ketosis? Ketosis is actually a normal metabolic process in your body that occurs when your body does not have enough glucose (sugar) for energy, so it burns up stored fat for energy instead (McIntosh, 2017). Ketones are produced as a by-product of this process, which can be measured on home test strips or finger prick tests. Once you can achieve ketosis, the fast gets much easier. It is recommended that you initially do a shorter fast, or experiment with a period of intermittent fasting before trying to do a prolonged water only fast.
- Orthstatic hypotension. This occurs when you get dizzy when you stand up suddenly. It is common when water fasting, but it can also be dangerous. The dizziness and risk of fainting could lead to an accident.
- Sudden death. Although it is rare, there is a chance of sudden death during a water fast. Granted these people did have pre-existing heart conditions, but it is still worth mentioning, particularly in the context of a prolonged water fast over 72 hours.
- Extreme hunger. Face it, hunger is uncomfortable. Although most hunger subsides after 3 days, the first few days can be unbearable, especially if you are surrounded by food. It is best to stay away from any sources of temptation during your fast so that makes it less intolerable.
IC & My Fasting Experience
What provoked me to do a water fast? I had persistent symptoms of urinary inflammation and pain, typical IC. Pain during urination, pain during intercourse and overall heightened sensitivity (mostly in my urethra). I also had digestive issues, gas, severe bloating, maldigestion and was prone to frequent UTIs.
I have experimented with both a 4.5 and a 7.5-day water fast. I did two 4.5 day fasts and one 7.5 days fast. Hands down, I will never do a fast longer than 4 days again! The 4 days were the most therapeutic for my body. It reduced my inflammation substantially and got me out of IC pain. It was also relatively easy to return back to eating normal foods again.
The first time I fasted was the hardest transitioning to ketosis (this is when your body switches from burning calories to burning fat cells instead and you do not feel that hungry anymore). It took me 3 days to achieve ketosis and I even passed out on day 3 due to orthstatic hypotension. I was very weak the entire fast and was very glad to break it.
The 7.5 day fast for me was not as eventful. I was better prepared to go into the fast and was able to achieve ketosis much quicker and had fewer problems overall. However, this one stressed my adrenals and my gut and it took me a long time to get it back to normal. I had indigestion for 8 days, diarrhea, knee and joint pain and even got a UTI after the fast! Luckily, I was able to resolve it rather quickly, but it taught me a lesson: prolonged water fasting is not for everyone.
Overall, I think the second fast was harder on my body because I have done several fasts in the past few months prior and it may have been too soon for me. There is a period of refeeding that is very important in the context of fasting, it is very important for stem cell proliferation of the immune cells. Therefore, it is possible I did not give my body enough time to rebuild new cells after the fast, and perhaps my immune system suffered as a result (Longo, 2018)
A word of advice: If you decide to fast, hire a health coach or nutritionist to help prepare you for your fast. You need have been following a comprehensive elimination diet full of good quality foods for a period of time before you fast to mitigate any negative side effects that could occur during or after the fast. You will also want them to run preliminary blood work on you to make sure you are healthy enough to fast. This will also help them guide you as to the duration of a fast that would be suitable for you.
- Cheng, C. W., Adams, G. B., Perin, L., Wei, M., Zhou, X., Lam, B. S., . . . Longo, V. D. (2014). Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression. Cell Stem Cell, 14(6), 810-823. doi:10.1016/j.stem.2014.04.014
- Glick, D., Barth, S., & Macleod, K. F. (2010). Autophagy: cellular and molecular mechanisms. J Pathol, 221(1), 3-12. doi:10.1002/path.2697
- Longo, V. (2018). Dr. Valter Longo on Resetting Autoimmunity and Rejuvinating Systems with Prolonged Fasting and the FMD. Retrieved (2018, July 19) from https://www.youtube.com/watch?v=evGFWRXEzz8&t=3361s
- Longo, V. D., & Mattson, M. P. (2014). Fasting: molecular mechanisms and clinical applications. Cell Metab, 19(2), 181-192. doi:10.1016/j.cmet.2013.12.008
- Longo, V. D., & Panda, S. (2016). Fasting, Circadian Rhythms, and Time-Restricted Feeding in Healthy Lifespan. Cell Metab, 23(6), 1048-1059. doi:10.1016/j.cmet.2016.06.001
- Mandal, A. (n.d.) What is Autophagy? Retrieved (2018, July 5) from https://www.news-medical.net/health/What-is-Autophagy.aspx
Exposure to toxins may have detrimental effects on humans and animals, even at low concentrations. Specific probiotic and bacterial strains may have properties that enable them to bind to toxins we are exposed to in our environment, such as food and water. Different strains vary in their ability to bind and detoxify, often times relying on pH, contact time, and viability on the binding capacities. Below are 3 bacterial strains and a summary of their mechanisms of action on human biochemistry regarding detoxification.
Mycotoxin Degradation – Mycotoxins are secondary metabolites produced by fungi, and are capable of producing disease and death in humans (Chlebicz & Slizewska, 2019). Humans are exposed to mycotoxins while consuming plant foods such as nuts (hazelnut, almonds, pistachios), peanuts, grains and some fruits. They are also exposed to them in the environment such as often reported in mold that is found in homes that have been water damaged. Aflatoxins are secondary metabolites of Aspergillus flavus and Aspergillus parasiticus, and it has been estimated that 4.5 billion of the world’s population is exposed to aflatoxins (Wild & Gong, 2010). The aflatoxins occur mostly in tropical regions with high humidity and temperature. They accumulate post-harvest when food commodities are stored under conditions that promote fungal growth. The naturally occurring aflatoxins are AFB1, AFB2, AFG1 and AFG2, with AFB1 the most abundant, toxic and carcinogenic, and are linked to liver cancer. “However, in agriculture, other adverse effects, including toxicity, growth and immune impairment, have been widely reported and these end points are rightly of increasing focus in studies of exposed people” (Wild & Gong, 2010).
Aflatoxin B1 (AFB1) is considered to possess the highest toxicity among various types of secondary metabolites produced by a larger number of Aspergillus spp., and classified as a Group I carcinogen for humans by the International Agency for Research on Cancer (Chlebicz & Slizewska, 2019). It has been reported that AFB1 could induce growth retardation, liver cancer, and may suppress immunity. Relevant studies indicated that AFB1was mostly metabolized by cytochrome P450 (CYP 450) enzyme systems after being absorbed in the GI tract. “Subsequently, under the action of CYP 450, including CYP1A2 and CYP 3A4, AFB1 was transformed to exo-AFB1-8,9-epoxide (AFBO), which could bind to DNA, proteins, and other critical cellular macromolecules to exert its carcinogenic effect” (Chlebicz & Slizewska, 2019).
Below are two probiotics that show promise in detoxification of mycotoxins:
- Saccharomyces cerevisiae var boulardii- (note the authors indicate that since S. cerevisiae and S. boulardii are closely similar in molecular structure, they should not be viewed as separate species taxonomically, so they have been renamed as saccharomyces cerevisiae van boulardii). Inhibition of mycotoxin absorption in the GI tract is one of the mechanisms of action of this strain. The mechanism of detoxification by yeast is due to the adhesion of mycotoxins to cell-wall components. In addition, this strain can biodegrade mycotoxins (such as AFB1) to prevent adsorption of these components inside the intestines on those who consume the food that is contaminated with the aflatoxin. As a side note, Saccharomyces cerevisiae var boulardii can also degrade phytates that are also found on many of the same foods that mycotoxins are found, and this may improve adsorption of iron, zinc, magnesium and phosphorus binding (Moslehi-Jenabian, Pedersen, & Jespersen, 2010). This could be viewed as a secondary mechanism involved in detoxification.
- L. plantarum—Lactobacillus species are also able to bind mycotoxins. Via hydrophobic interactions, they are able to bind to mostly cell wall peptidoglycans, polysaccharides and teichoic acid (Chlebicz & Slizewska, 2019). L. plantarum has demonstrated to have good AFB1binding ability in vitro. It can also “increase fecal AFB1excretion, reduce lipid peroxidation, and reverse antioxidant defense systems to alleviate AFB1 toxicity” (Chlebicz & Slizewska, 2019). L. plantarum may also play a role in the suppression of CYP1A2 and CYP3A4 expression to enhance glutathione-conjugating activity and promote detoxification (Chlebicz & Slizewska, 2019). It has been reported that some lactic acid bacteria such as L. plantarum can remove AFB1 or have protective effects against AFB1. Some relevant studies demonstrated that lactobacilli could inhibit the production of aflatoxin as well as the growth of Aspergillus spp. (Huang et al., 2017). L. plantarum also demonstrates strong free radical scavenging activities and can improve antioxidant status, protecting against the effects of AFB1. “L. plantarum might also act as a biological barrier in the intestine under normal conditions, thereby reducing the bioavailability of AFB1 ingested orally and hence avoiding its toxic effects” (Chlebicz & Slizewska, 2019). I attached a chart that demonstrates some of the mechanisms of L. plantarum on detoxification of AFB1., which includes increasing AFB1 excretion, decreasing AFB1 epoxidation catalyzed by CYP1A2 and CYP3A4, coupled with enhancing the activities of different antioxidant enzymes and GST detoxification which are connected with the NrF2 signaling pathway (Chlebicz & Slizewska, 2019).
- Bacillus subtilis– This spore forming species of bacteria had some interesting mechanisms in detoxification.
Cypermethrin belongs to a group of synthetic pyrethroid insecticides which widely used in agriculture, forestry, horticulture, public health and households for the protection of textiles and to check pest infestation (Gangola, Sharma, Bhatt, Khati, & Chaudhary, 2018). . Cypermethrin is also constitute common ingredients of household insecticides (Gangola et al., 2018). Cypermethrin is an environment pollutant because of its widespread use and toxicity. Persistence may lead to serious damage to non-target organisms and various ecosystem (Gangola et al., 2018). Metabolism of cypermethrin is important because cypermethrin possess antimicrobial activities hence it prevents the beneficial microflora.
The mechanism of action is the laccase enzyme that can degrade the pesticide. Bacillus subtilis strain demonstrated to completely metabolize cypermethrin in just 15 days under laboratory conditions. The bacterial isolate harbors the metabolic pathway for the detoxification of the cypermethrin. It can also completely degrades cypermethrin without leaving any persistent or toxic metabolite (Gangola et al., 2018).
Heavy metals (Syed & Chinthala, 2015)
It is estimated that over one billion human beings are currently exposed to elevated concentrations of toxic metals and metalloids in the environment. It is also estimated that several million people may be suffering from subclinical metal poisoning. “In addition, adverse effect of heavy metals includes suppression of the immune system and carcinogenicity, neurotoxicity, mainly in children, and inhibition of the activity of some critical enzymes related to synthesis of vital biomolecules along with accumulation in the body of different organisms causing biomagnifications” (Syed & Chinthala, 2015). B. subtilis has greater ability to bind metals than Gram-negative ones due to their different cell wall structures (Cai et al., 2018). Interestingly, bacterial isolates of B. subtilis showed significant biosorption of lead. Heavy metal biosorption is the ability of bacterial cells or components to adsorb, chelate, or precipitate metal ions in the solution into insoluble particles or aggregates which can be removed either by sedimentation or filtration from the solution. Lead biosorption modifies groups like carboxyl, hydroxyl, and amino where other metal ions cannot compete offering it more affinity. The main agents in the uptake of heavy metals by B. subtilis are carboxyl groups, the sources of which are the teichoic acids associated with the peptidoglycan layers of the cell wall (Cai et al., 2018).
Cai, Y., Li, X., Liu, D., Xu, C., Ai, Y., Sun, X., . . . Yu, H. (2018). A Novel Pb-Resistant Bacillus subtilis Bacterium Isolate for Co-Biosorption of Hazardous Sb(III) and Pb(II): Thermodynamics and Application Strategy. Int J Environ Res Public Health, 15(4). doi:10.3390/ijerph15040702
Chlebicz, A., & Slizewska, K. (2019). In Vitro Detoxification of Aflatoxin B1, Deoxynivalenol, Fumonisins, T-2 Toxin and Zearalenone by Probiotic Bacteria from Genus Lactobacillus and Saccharomyces cerevisiae Yeast. Probiotics Antimicrob Proteins. doi:10.1007/s12602-018-9512-x
Gangola, S., Sharma, A., Bhatt, P., Khati, P., & Chaudhary, P. (2018). Presence of esterase and laccase in Bacillus subtilis facilitates biodegradation and detoxification of cypermethrin. Sci Rep, 8(1), 12755. doi:10.1038/s41598-018-31082-5
Huang, L., Duan, C., Zhao, Y., Gao, L., Niu, C., Xu, J., & Li, S. (2017). Reduction of Aflatoxin B1 Toxicity by Lactobacillus plantarum C88: A Potential Probiotic Strain Isolated from Chinese Traditional Fermented Food “Tofu”. PLoS ONE, 12(1), e0170109. doi:10.1371/journal.pone.0170109
Moslehi-Jenabian, S., Pedersen, L. L., & Jespersen, L. (2010). Beneficial effects of probiotic and food borne yeasts on human health. Nutrients, 2(4), 449-473. doi:10.3390/nu2040449
Syed, S., & Chinthala, P. (2015). Heavy Metal Detoxification by Different Bacillus Species Isolated from Solar Salterns. Scientifica (Cairo), 2015, 319760. doi:10.1155/2015/319760
Wild, C. P., & Gong, Y. Y. (2010). Mycotoxins and human disease: a largely ignored global health issue. Carcinogenesis, 31(1), 71-82. doi:10.1093/carcin/bgp264
Acetaminophen (APAP) (brand name Tylenol) is a commonly used xenobiotic over the counter pain medication, as most people falsely assume that it is safe. In fact, I wish I knew this before I was giving Tylenol to my own children for their ear infections and fevers! With the toxic buildup that we encounter, it is no surprise there is a rise with so many chronic health issues such as autoimmune diseases, CV disease, neurological conditions, infertility and many more. I have not yet obtained clarity from research if Tylenol is harmful in smaller doses, since most of the literature indicates that Tylenol is safe in recommended doses (NIH, n.d). Acetaminophen differs from NSAID’s in its mechanism of action. Rather than influencing the COX-1 and COX-2 enzymes, it producing analgesia by increasing pain thresholds through inhibition of the NO pathway that is activated by many pain NT receptors (NIH, n.d.). The recommended oral dose is 660 to 1000 mg every 4 to 6 hours, but should not to exceed 3 grams per day (NIH, n.d). It is also frequently found in many OTC cold medications and antihistamines as well. Common products in the United States include: Tylenol-PM, Nyquil, Darvocet, Vicodin, and many others. Acetaminophen is one of the most commonly used medications in the United States and more than 25 billion doses are sold yearly.
The liver, and to a lesser extent the kidney and intestine are involved in the metabolism of acetaminophen (Mazaleuskaya et al., 2015). “It involves a complex inter-organ transport of metabolites between the liver, kidney and intestine, through bile and the blood stream, to be ultimately be eliminated in the urine” (Mazaleuskaya et al., 2015).
Unfortunately, Tylenol is often associated with hepatotoxicity. Chronic use of this OTC drug in doses of 4 grams per day have been found to lead to transient levels of serum aminotransferase levels, generally starting after 3 to 7 days, with peak values rising 3-fold in 39% of people (NIH, n.d.). Standard use can lead to severe hypersensitivity reactions including Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) which can cause serious liver injury. The best-known form of hepatoxicity is due to overdose, which can result in large elevation of ALT and AST within 48 to 96 hours after ingestion, including jaundice, confusion, liver failure and death.
Xenobiotic metabolism of Acetaminophen
APAP is extensively metabolized by the liver via three main hepatic pathways: glucuronidation, sulfation, and CYP450 2E1 oxidation (Dimitropoulos & Ambizas, 2015). About 90% of APAP is conjugated to sulfation and glucuronidase metabolites. From the liver, most of the glucuronide and sulfate metabolites get transported through the intestines into the blood. The kidney is the main site of the disposition of the APA-sulfate. However, cytochrome P450 (CPY) enzymes are also involved in converting approximately 2% of acetaminophen to a highly reactive metabolite known as N-acetyl-pbenzoquinonimine (NAPQI). NAPQI is highly reactive and is primarily associated with the hepatoxicity of acetaminophen (Mazaleuskaya et al., 2015). Under normal circumstances, this toxic metabolite reacts with sulfhydryl groups in glutathione, converting it to harmless metabolites before being excreted in urine (Dimitropoulos & Ambizas, 2015). Although most of the NAPQI is formed in the liver, the kidney also metabolizes APAP to toxic metabolites and releases cysteine conjugate of APAP into the bile and blood for even more elimination in the urine (Mazaleuskaya et al., 2015). In human liver microsomes, CYP enzymes (CYP2E1 and CYP1A2) were first reported to convert high doses of APAP to NAPQI. Other enzymes are reported to be involved, such as CP2A6, CYP2D6, CPY3A4 although role of the latter enzyme is still up for debate (Mazaleuskaya et al., 2015). At very high doses, the sulfation pathway becomes saturated, glucuronidation and oxidation increase, and higher amounts of the drug get oxidized to the reactive NAPQI. The problem is, excess NAPQI eventually depletes glutathione stores and can target mitochondrial proteins and ion channels leading to loss of ATP production, ion misbalance and cell death (Mazaleuskaya et al., 2015). That is why replacement of glutathione with NAC (precursor to glutathione) is useful for APAP toxicity (Moyer et al., 2011)
Glucuronidation of APAP is catalyzed by the enzyme UDP-glucuronosyl transferases (UGT), which makes APAP molecule water soluble for excretion. Sulfation is carried out by a group of cytosolic enzymes called sulfotransferases (SULT), which makes it more polar and prone to elimination. “Using human platelet homogenates as a model for xenobiotic metabolism in the liver, SULT1A1 and SULT1A3/4 were first shown to catalyze APAP sulfation” (Mazaleuskaya et al., 2015). Genetic variability in SULT and GST genes are not well established, and only a few studies have been conducted in relation to GST polymorphisms and acetaminophen detoxification (Mazaleuskaya et al., 2015). However, studies on polymorphisms in detoxification genes for the enzymes involved in APAP metabolism can be an opportunity for future applications of preventative treatment of APAP toxicity in susceptible individuals.
Enzymatic breakdown of APAP:
General phase I support:
B vitamins (B2, B3, B6, B12), folate, glutathione, Vitamin E, Vitamin C, Zinc, BCAA’s
Antioxidant protection from intermediate metabolites:
Vitamin A, Vitamin C, Vitamin E, Selenium, Zinc, Copper, Manganese, Coq10, Bioflavonoids
General phase II support:
NAC, glycine, taurine, glutamine, cysteine, methionine
Inducers of CYP2E1 enzyme (for low activity) (Hodges & Minich, 2015):
Fish oil, chicory root
Inhibitors of CY2PE1 enzyme (for overactivity) (Hodges & Minich, 2015):
Garlic, watercress, NAC, ellagic acid, green tea, black tea, dandelion, chrysin, MCT’s
Inducers of glucuronidation (for low activity):
Flavonoids- quercetin (Glucuronidation, n.d.)
Inhibitors of glucuronidation (for overactivity):
Probiotics (Glucuronidation, n.d.)
Calcium-D-glucarate Glucuronidation, n.d.)
Inducers of sulfation (Hodges & Minich, 2015):
Coffee, cocoa, black tea, green tea, vitamin A, Liver, fish, eggs, and fruits and vegetables with vitamin A
Dietary sources of sulfur (Hodges & Minich, 2015):
Fish, shellfish, lamb, beef, turkey, eggs, cabbage, broccoli, Brussel sprouts, apricots, peaches, spinach, watercress, horseradish, brazil nuts, almonds, peanuts, walnuts, mustard, ginger
Food contradicted while using APAP:
Alcohol– Ethanol induced oxidative stress is a major mechanism in which ethanol can cause liver injury, particularly via the CYP2E1 enzymatic pathway (Lu & Cederbaum, 2008). Levels of CYP2E1 are elevated under a variety of physiological and pathophysiological conditions, and after acute and chronic alcohol treatment.
High cholesterol fast food-Fast food can mediate CYP2E1 associated liver fibrosis by promoting oxidative stress, inflammation, endotoxemia and insulin resistance (Abdelmegeed et al., 2017)
Abdelmegeed, M. A., Choi, Y., Godlewski, G., Ha, S. K., Banerjee, A., Jang, S., & Song, B. J. (2017). Cytochrome P450-2E1 promotes fast food-mediated hepatic fibrosis. Sci Rep, 7, 39764. doi:10.1038/srep39764
Dimitropoulos, E.; Ambizas, E.; (2015). Acetaminophen Toxicity: What Pharmacists Need to Know. Retrieved (2019, April 30) from https://www.uspharmacist.com/article/acetaminophen-toxicity-what-pharmacists-need-to-know
Glucoronidation. (n.d.) Retrieved http://www.herbaltransitions.com/Glucuronidation.html
Hodges, R. E., & Minich, D. M. (2015). Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application. J Nutr Metab, 2015, 760689. doi:10.1155/2015/760689
Lu, Y., & Cederbaum, A. I. (2008). CYP2E1 and oxidative liver injury by alcohol. Free Radic Biol Med, 44(5), 723-738. doi:10.1016/j.freeradbiomed.2007.11.004
Mazaleuskaya, L. L., Sangkuhl, K., Thorn, C. F., FitzGerald, G. A., Altman, R. B., & Klein, T. E. (2015). PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics, 25(8), 416-426. doi:10.1097/fpc.0000000000000150
Moyer, A. M., Fridley, B. L., Jenkins, G. D., Batzler, A. J., Pelleymounter, L. L., Kalari, K. R., . . . Weinshilboum, R. M. (2011). Acetaminophen-NAPQI hepatotoxicity: a cell line model system genome-wide association study. Toxicol Sci, 120(1), 33-41. doi:10.1093/toxsci/kfq375
National Institute of Health (n.d.) Acetaminophen. Retrieved (2019, April 30) from https://livertox.nih.gov/Acetaminophen.htm
For this review, I want to summarize the findings on the dietary carbohydrate to protein ratio and how it may influence body composition and blood lipid profiles in adult women.
There is evidence that older adults experience age-related changes in body composition, such as increase in body fat and decrease in lean body mass (Kim, O’Connor, Sands, Slebodnik, & Campbell, 2016). A moderate energy restricted diet is often an effective way for overweight adults to reduce bodyfat mass, and improve their health profile, but it often comes with the price of a loss of 25% of body mass being lost as lean body mass (Kim et al., 2016). Accumulating data suggests that increased protein content of the diet, in combination with exercise training, can reduce the loss of lean body mass in overweight and obese subjects following a weight loss diet. This preservation of lean body mass has been attributed to the increased level of essential amino acids, especially leucine, provided by the protein (Mettler, Mitchell, & Tipton, 2010).
Current dietary guidelines recommend a daily macro-nutrient intake of 55% carbohydrate, 30% protein and 15% fat (Layman et al., 2003). However, this balance has been challenged by evidence from epidemiological, clinical and experimental studies, reporting that a higher carbohydrate intake can reduce oxidation of body fat and increase blood triglycerides (Layman et al., 2003). In particular, the optimal ratio of carbohydrate to protein has been challenged on the basis of glucose homeostasis in the context of body mass reduction. Under a higher carbohydrate intake, the body has to rely on insulin to metabolize and dispose large quantities of dietary glucose, whereas under lower carbohydrate intakes (<200g per day), the body would rely more on hepatic production to maintain blood glucose via gluconeogenesis or glycogenolysis (Layman et al., 2003).
A study conducted in 2003 by Layman et al (2003), compared the results of a moderate protein and lower carbohydrate intake to a higher carbohydrate with lower protein intake, and the influence on body mass and blood lipids. In this study, the total energy intake, fat and fiber were consistent among the two groups: 1700 kcal/day, total fat intake was 50g/day and total fiber at 20g per day. In the higher protein group (Protein Group) protein intake averaged 125g/day with a carbohydrate intake of 171g/day. The higher carbohydrate group (CHO) consisted of 68g pf protein per day and 239g of carbohydrates. The relative proportions of energy in the Protein Group were 30% protein, 41% carbohydrate and 29% fat with a ratio of carbohydrate to protein (CHO/protein) of 1.4. The proportion in the CHO Group was 16% protein, 58% carbohydrate and 26% fat with a ratio of 3.5 (Layman et al., 2003). Obviously, the cholesterol and saturated fatty acid intake was higher in the Protein group than the CHO group.
The study duration was 10 weeks. The results of the study indicated the following:
- There was not a big change in body weight between the two groups. The Protein Group lost a total weight of 7.53kg and the CHO group lost 6.96kg.
- Changes in body composition indicate the weight loss was mostly bodyfat. The Protein group lost 14.4% of initial body fat, the CHO group lost 12.2% of initial bodyfat. Loss of lean body mass tended to be greater in the CHO Group compared to the Protein Group. When changes in body composition were expressed as a ratio of fat/lean loss, the Protein group achieved a fat/lean loss of 6.36 vs. 3.92 in the CHO group. The higher protein group clearly had a stronger improvement in body composition.
- There were some differences seen in thyroid hormones, blood lipids and fasting and postprandial glucose and insulin levels, but it was not explained in detail as it was not the main objective of this study.
In summary, the results of this study indicate that the positive changes in body composition associated with the higher protein diet may be associated with either targeting of body fat or sparing of muscle protein, or both. For the purposes of improving body composition, a higher protein diet may be effective for adults.
Before I end this summary, I do want to mention I did stumble upon an interesting study in 2016 that indicates that a high protein intake eliminates the weight loss induced improvement of insulin action on postmenopausal women (Smith et al., 2016). This study indicates that a high protein diet can have adverse effects on postprandial insulin sensitivity. According to the authors, “the beneficial effect of 10% weight loss on muscle insulin action (assessed as glucose disposal rate and phosphorylation of AKT in muscle during a HECP) was eliminated by high protein (HP) intake” (Smith et al., 2016). The failure to improve muscle insulin sensitivity in the higher protein group is clinically important, because it reflects a failure to improve a major mechanism involved in the development of T2D. It also indicates more insulin is required in the higher protein group to dispose of a given amount of glucose. This can be due to:
- BCAA’s, particularly leucine, that can impair insulin mediated uptake of glucose through a negative feedback inhibition
- There may be an association of glycine and tryptophan and metabolites of acylcarnitine in the development of insulin resistance, regardless of the amount of circulating amino acid metabolites measured in the serum.
- There may be a metabolic process related to oxidative stress that is expressed in the higher protein group, as evidenced by gene expression of GSTA4 and PRDX3 that are both associated with oxidative stress. These results suggest that the adverse effect of high protein intake on insulin action during weight loss therapy may have been mediated through its effects on oxidative stress because it prevented the WL-induced decrease, and even increased, metabolic pathways involved in oxidative stress response in muscle.
- Both groups had improved liver insulin sensitivity, but the higher protein group experienced a reduction in muscle insulin sensitivity. This is attributed to the fact that protein is a potent insulin secretagogue, which may overcome the adverse effect of protein on insulin sensitivity by increasing the secretion of insulin (Smith et al., 2016).
I must mention however, protein causes greater satiation and has a greater thermogenic effect of feeding than carbohydrate and fat. This alone can lead to greater weight loss with a higher protein than a standard protein diet. “Therefore, the adverse effect of dietary protein on muscle insulin action could be offset by its effect on hepatic insulin sensitivity, insulin secretion and energy balance” (Smith et al., 2016).
In summary, this review demonstrates that the protein content of a weight loss diet can have significant effects on metabolic function and weight loss outcome. I personally believe that diets should be personalized for the individual. A high protein diet is not suitable for everyone. Neither is a high carbohydrate diet. The individual’s needs should be taken into consideration, along with various markers of health that can be measured in a blood chemistry panel, their nutritional needs (such as macronutrient deficiencies) and even nutrigenomics, health predispositions and family history. The one size fits all approach is not appropriate when prescribing nutrition therapy, as the results of these studies also demonstrate.
What do I think? The evidence is good for a higher protein diet, but I wonder if they looked into the glucogenic amino acids and their effect on insulin sensitivity. In my review, I found another journal that indeed indicated that various amino acids can actually decrease insulin sensitivity. Interestingly, it was leucine that was contributing to this change in muscle insulin sensitivity, and that is actually a ketogenic amino acid! If I find the free time at some point, I would love to research the effects of glucogenic and ketogenic amino acids and how they affect insulin sensitivity and type 2 diabetes. I personally have not been a fan of high protein diets. I feel it is too hard on the kidneys, and considering glycine is often a problem with oxalate metabolism, especially in the context B1 deficiency, I feel the risk of kidney stones is too great to recommend high protein across the board (See image). I prefer a more balance approach, with a balance of macronutrients and incorporating intermittent fasting as a way to improve blood lipids and insulin sensitivity.
Kim, J. E., O’Connor, L. E., Sands, L. P., Slebodnik, M. B., & Campbell, W. W. (2016). Effects of dietary protein intake on body composition changes after weight loss in older adults: a systematic review and meta-analysis. Nutr Rev, 74(3), 210-224. doi:10.1093/nutrit/nuv065
Layman, D. K., Boileau, R. A., Erickson, D. J., Painter, J. E., Shiue, H., Sather, C., & Christou, D. D. (2003). A Reduced Ratio of Dietary Carbohydrate to Protein Improves Body Composition and Blood Lipid Profiles during Weight Loss in Adult Women. J Nutr, 133(2), 411-417. doi:10.1093/jn/133.2.411
Mettler, S., Mitchell, N., & Tipton, K. D. (2010). Increased protein intake reduces lean body mass loss during weight loss in athletes. Med Sci Sports Exerc, 42(2), 326-337. doi:10.1249/MSS.0b013e3181b2ef8e
Smith, G. I., Yoshino, J., Kelly, S. C., Reeds, D. N., Okunade, A., Patterson, B. W., . . . Mittendorfer, B. (2016). High-Protein Intake during Weight Loss Therapy Eliminates the Weight-Loss-Induced Improvement in Insulin Action in Obese Postmenopausal Women. Cell Rep, 17(3), 849-861. doi:10.1016/j.celrep.2016.09.047
During the past two decades, there has been a rapid increase in studies that report associations with gene polymorphisms, nutrition and disease risk (Burdge, Hoile, & Lillycrop, 2012). This is a paradigm shift from traditional nutritional recommendations that have been based on age, sex, and pregnancy. The advances in the association with epigenetics and nutritional requirements have been the driver of the advancement in the field of nutrigenomics, which has been wildly exploding.
What is epigenetics? We learned in middle school that our genetic code is the sequence of nucleotides in our DNA, which can certainly influence health status. However, I was amazed when I learned for the first time that there is another set of instructions that affects our gene expression, and this set of instructions can actually influenced by our environment such as our diet! This is referred to as epigenetics. I remember learning in my Biology Masters that Epigenetics meant “above the genome”. Epigenetics is the “study of heritable changes in gene function that occurs independent of a change in DNA sequence” (Kauwell, 2008) which involves a group of modifications that do not alter the actual DNA structure, but rather chromatin structure that can regulate transcription. “The major epigenetic processes are DNA methylation, histone modification, and noncoding RNA’s” (Burdge et al., 2012).
As we learned once in college, through the process of meiosis, there are multiple ways that diversity occurs among our genotypes to ensure no two genotypes are alike (well, except in the case of identical twins). These include crossing over, independent assortment, and random fertilization. This creates genetic uniqueness that is a result of variations in our DNA in which one nucleotide is substituted for another at specific locations on our genome, often called SNP’s (single nucleotide polymorphism) (Kauwell, 2008). We are finding out that SNP’s can alter certain nutrient requirements and metabolism, and although they do not affect regions that code for proteins, they do affect events that occur at the molecular levels such as transcription factor binding to the promoter region of the gene, which can thus alter the expression of that gene. Studies with identical twins have demonstrated some interesting results in the role environment indeed can play a role as seen in insights from identical twins (Learn Genetics, n.d.).
One common nutritionally relevant SNP that is a hot topic in functional medicine occurs on the MTHFR gene which provides instructions for making an enzyme called methylenetetrahydrofolate reductase. This enzyme plays a role in processing amino acids such as homocysteine to methionine (NIH, n.d.). This SNP involves the substitution of cytosine with thymine (C->T) at the base pair 677 of the gene, that results in a coding change where alanine is replaced with valine at position 222 in the gene product (Kauwell, 2008). Inheriting one or two copies of this gene variant can down-regulate the enzyme function, which has some health implications. For example, someone with two copies of the gene (homozygous) may experience elevated plasma homocysteine, especially when paired with low folate status (Kauwell, 2008). This can put the person at risk for coronary artery disease. “Fortunately, reduced MTHFR activity associated 677C->T polymorphism is attenuated when folate status is adequate” (Kauwell, 2008).
What is fascinating about our epigenome is that it provides an extra layer of instructions besides our genetic sequence that codes for proteins synthesized by our bodies. This “extra layer of instructions” can affect whether certain genes are turned on or off, which can thus affect cellular function and metabolism. In fact, the environment has a strong influence on these instructions, such as nutrient status from food and supplements, which can alter the epigenetic state of the genome and subsequent gene expression. What this means is that the same exact DNA sequence for a particular gene may give rise to different outcomes based on things like diet-induced epigenetic modifications that can influence gene silencing and activation.
This is an exciting time for the field of nutrition and nutrigenomics, as we are finding increasing evidence that nutrition throughout the life course can modify the epigenome in such a way that can influence risk of a number of important diseases. “Therefore, if nutritional recommendations are to be targeted at individuals then epigenetic effects must be included in any attempt at personalized nutrition” (Burdge et al., 2012).
Burdge, G. C., Hoile, S. P., & Lillycrop, K. A. (2012). Epigenetics: are there implications for personalised nutrition? Curr Opin Clin Nutr Metab Care, 15(5), 442-447. doi:10.1097/MCO.0b013e3283567dd2
Kauwell, G. P. (2008). Epigenetics: what it is and how it can affect dietetics practice. J Am Diet Assoc, 108(6), 1056-1059. doi:10.1016/j.jada.2008.03.003
Learn Genetics. Insights from Identical Twins. Retrieved (2019, April 25) from https://learn.genetics.utah.edu/content/epigenetics/twins/
NIH (n.d.) MTHFR gene. Retrieved (2019, April 25) from https://ghr.nlm.nih.gov/gene/MTHFR