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
Milk protein (Casein)
Milk protein hypersensitivity is thought to affect well over 40% of the population. Milk protein intolerance causes a delayed response, where it can take up to 3 days to cause symptoms. These delayed reactions to milk proteins are often tested for by measuring milk-specific IgG antibodies in blood.
Milk hypersensitivity is an IgG-mediated response (often called type III hypersensitivity reactions), and is different than an allergy which is IgE-mediated. Milk hypersensitivity in early childhood is mostly an IgE-mediated response to casein, causing immediate reactions (Anthoni, Savilahti, Rautelin, & Kolho, 2009). However, IgE reactions are often rare in adulthood. Instead, a hypersensitivity in adulthood is usually Ig-G mediated.
Many symptoms resemble irritable bowel (IBS), such as bloating, constipation, migraines, headaches, runny nose, sinusitis, fatigue, skin rashes, eczema and low mood.
Egg Protein (ovalbumin)
An egg hypersensitivity typically is associated with the egg white (albumen). This differs from an egg allergy in which involves the entire egg and is characterized by immediate allergic symptoms associated with histamine (runny nose, sneezing, watery eyes, wheezing, eczema). Egg allergies are also more common among children.
An egg hypersensitivity is characterized by gastrointestinal symptoms such as excessive gas, nausea, stomach pain, and stomach cramping. Additionally, an egg hypersensitivity can reveal itself in other symptoms such as headaches, skin problems, difficulty breathing, heart burn, joint pain, irritability and nervousness. Symptoms usually come on gradually and can be dose-dependent, and is often not life threatening.
The immune response to proteins such as egg and dairy
In normal conditions, consumed proteins, including food allergens, are completely degraded in the digestive tract to oligopeptide fragments (Gocki & Bartuzi, 2016). However, 15% of protein is often found to be incompletely digested, including a proportion of food antigens. Food antigens that were not destroyed by digestive processes (such as enzymes, bile salts, gastric pH) penetrate the intestinal epithelium of the digestive tract and reach the body’s internal environment (Gocki & Bartuzi, 2016). There are four main steps involved in the immune reaction (Gocki & Bartuzi, 2016):
- Capture of antigens by Peyer’s patch M cells, which is the microfold cell. Here there are dendritic cells, macrophages, T cells and B cells.
- Capture of antigens from the digestive tract by dendritic cell processes localized by enterocytes.
- This is where it is processed to present in an MHC molecule. The dentritic cell phagocytoses the antigen and presents a peptide of the food to CD4 T cells. CD4 binds to CD28 which evokes a TH1 response. The TH1 cell produces interferon gamma, which then initiates B cell to make IgG.
- Interferon gamma will also cause CD8 T cells specific for the food to activate macrophages to produce reactive oxygen species (contributing to oxidative stress and gut inflammation). This can contribute to production of IL-1, IL-6 and even more TNF-a (Zwickey, 2018).
- Capture of antigens by enterocytes. Food antigens can also travel between enterocytes where they can damage the integrity of the cells.
- Food antigens encounter cells of the GALT (gut-associated lymphoid tissue)
- Here, food allergens will be treated by GALT either as “innocuous antigens and induce tolerance, or as pathogens and then cause either defense reactions or excessive defensive reactions, that is hypersensitivity” (Gocki & Bartuzi, 2016).
It is also important to note that TH1 also makes TNF-alpha, which is a cytokine associated with breaking down tight junctions and leaky gut. This is also contributing to many of the symptoms associated with a hypersensitivity reaction, such as GI disturbances.
Interestingly, there is a genetic component to food hypersensitivities, making some individuals more susceptible to the loss of oral tolerance; either oral tolerance is not established or it is degraded. In fact, within the first year after birth, approximately 2.5% of infants have a cow’s milk hypersensitivity, and 80% go on to outgrow it by the time they reach five years of age. On the other hand, approximately 60% of milk allergies are mediated by immunoglobulin E (IgE) rather than by immunoglobulin G (IgG)—as is seen with hypersensitivity reactions (Sampson, 2003).
Anthoni, S., Savilahti, E., Rautelin, H., & Kolho, K. L. (2009). Milk protein IgG and IgA: the association with milk-induced gastrointestinal symptoms in adults. World J Gastroenterol, 15(39), 4915-4918.
Food Intolerances. (2014, May 6). Milk Allergy or Intolerance? Retrieved 2018, May 11 from https://www.yorktest.com/milk-allergy-or-milk-intolerance/
Gocki, J., & Bartuzi, Z. (2016). Role of immunoglobulin G antibodies in diagnosis of food allergy. Postepy Dermatol Alergol, 33(4), 253-256. doi:10.5114/ada.2016.61600
Sampson, H. A. (2003). 9. Food allergy. Journal of Allergy and Clinical Immunology, 111(2), S540-S547. doi:10.1067/mai.2003.134
Zwickey, Heather. (n.d). Immune Response to Food. [presentation] Retrieved (2018, May 11) from https://learn.muih.edu/courses/6679/modules
I was interested in learning more about vitamin E supplementation to address oxidative stress. Dr. Tan wrote a nice summary of Vitamin E in his book “The Truth about Vitamin E”. Vitamin E is a family of eight separate but related molecules, and that includes four tocopherols (delta, gamma, alpha and beta) and four tocotrienols (also delta, gamma, alpha and beta). For many years, the nutrition world focused on tocopherols because it was discovered first. Only in the last decade did tocotrienols start to shine in its delta and gamma molecules and it was found that combined with a healthy lifestyle, it can lower lipids, reduce inflammation, protect the liver, promote bone health, facilitate in eradicating cancer cells and increase survival in cancer patients. In fact, studies demonstrate that the “wrong” form of vitamin E (tocopherols) can actually hinder the body’s ability to absorb the “right form” (tocotrienols).
A few interesting things about tocotrienols:
- Delta tocotrienol help maintain the membrane integrity of the cell membrane to protect cellular functions. Phospholipids, cholesterol and a small amount of protein make up most of the cell membrane, creating a lipid bilayer which is important for water, oxygen and CO2 to cross the membrane while blocking out other larger potentially harmful substances
- It can protect the cell from free radical damage
- Antioxidants like vitamin E (C, A, and selenium and zinc) can give the free radical its own electron without destabilizing the cell. Others include resveratrol, curcumin, astaxanthin, lutein, Coq10. Tocotrienols are well suited to protect the cell membrane because their perfect fit into the lipid bilayer allows them to better protect the lipids within this bilayer from oxidation.
The delta- and gamma-tocotrienols spread out and attach themselves to a variety of cell membranes throughout your body and then start patrolling for free radicals. As soon as they sense one closing in (meaning the free radical attaches to a fatty acid in the cell wall), the tocotrienol molecule releases an electron which re-attaches to the free radical, making the damaged (oxidized) fatty acid in the cell wall whole again. The free radical is stable again and leaves the cell. Put simply, the tocotrienol removes the dysfunctional oxygen from the fatty acid.
What is the difference between tocotrienols and tocopherols? First, they are 40-60 times more potent.
Here are some key differences:
- Tocotrienols have shorter tails that do not anchor deeply into the cell membrane- which allows them to move around the cell 50x faster to intercept free radicals more easily. In contrasts to tocopherols that have a longer tail, anchor deeply into cell membranes, and move more slowly. Because of this it is thought that tocotrienols are 40-60x better at giving one of their electrons to invading free radicals and repairing damage to lipids on membranes
- Tocotrienols have a smaller head and delta tocotrienols have the smallest- allowing them to squeeze in parts of the cell easier, giving them wider access to membranes and increasing their ability to capture more free radicals
- Tocotrienols have unsaturated tails where tocopherols have saturated tails- making them unique in that they have double bonds in their tails and can provide more lipid oxidation protection because of superior bioavailability to cell membranes.
I also want to point out that tocotrienols are great for reducing chronic inflammation. Studies demonstrate that alpha, gamma and delta tocotrienols strongly inhibit NFkB and TNF-a, along with other pro-inflammatory cytokines. “Among the most notable biomarkers to be affected by a 250 mg tocotrienol daily dosage were C-reactive protein (CRP; a predictor for chronic inflammation), nitric oxide (NO), and malondialdehyde (MDA), with decreases of 40%, 40%, and 34%, respectively” (Barrie, nd).
Tocotrienols can increase total antioxidant status. Total antioxidant status also increased by 22%, suggesting that delta-tocotrienol can potentiate endogenous antioxidants. This is great news for the use of tocotrienols for reduce inflammation associated with high cholesterol, CV disease, metabolic syndrome, nonalcoholic fatty liver disease, diabetes and pre-diabetes. It also can play a role in cancer, bone and brain health.
Tocotrienols area great for eye health. Interestingly, delta-tocotrienols may also delay the beginning of cataracts when applied to the eye due to reduced oxidative stress and nitrosative stress to the lenses which are exposed to environmental oxidants. Tocotrienol had a beneficial effect on lens antioxidant enzymes, including superoxide dismutase and catalase, both of which returned to normal levels with the topical treatment. Furthermore, tocotrienol significantly decreased malondialdehyde, a lipid peroxidation end product found to be high in cataracts, and restored the lens soluble to insoluble protein ratio to normal levels.
And finally, it has positive influence on the immune system. One study showed that annatto tocotrienol combined with antibiotics had the greatest efficacy in decreasing bacteria when compared with tocotrienol or antibiotic treatment alone (Tan, n.d). This may be due to an influence that tocotrienols have on T cells.
Tan, Barrie. The Truth about Vitamin E: The Secret to Thriving with Annatto Tocotrienols . Kindle Edition.
Zinc is a very interesting mineral. It is also one I commonly see low in hair tissue mineral analysis (HTMA).
It plays an important role in facilitating hundreds of biochemical reactions. Due to its role in enzymatic function, it can impact metabolic pathways such as carbohydrate, protein, nucleic acid, and lipid metabolism. It is also a structural component in thousands of transcription factors and can affect gene expression that impacts many physiological processes in the body. “Zinc appears to be part of more enzyme systems than all the rest of the trace minerals combined; over 300 enzymes from every enzyme class (oxidoreductases, hydrolases, lyases, isomerases, transferases, and ligases) require zinc” (Gropper, n.d.). Some of these zinc dependent enzymes include:
- Carbonic anhydrase: acid base balance- found in erythrocytes and renal tubule cells, essential for maintaining acid-base balance/buffering and respiration. The enzyme catalyzes the reaction that allows rapid disposal of carbon dioxide. Activity of this enzyme in red blood cells diminishes with chronic low zinc status in the diet.
- Alkaline phosphatase: Contains four zinc atoms per enzyme molecule, in which two are required for enzyme activity. This enzyme is found in bones and the liver.
- Alcohol dehydrogenase: contains 4 zinc molecules per enzyme molecule, two are required for catalytic activity. This enzyme is important in the NADH-dependent conversion of alcohols to aldehydes. For example, this enzyme converts retinol (form of Vitamin A) to retinal, which is needed for night vision. It also is required for acetyl aldehyde for alcohol metabolism
- Carboxypeptidases A and B and Aminopeptidases- which is involved in protein digestion. These enzymes are secreted by the pancreas into the duodenum. Zinc is bound tightly to carboxypeptidases and is essential for enzymatic activity; in fact, enzyme activity decreases with zinc deficiency (Gropper, n.d.). Aminopeptidases consist of a group of enzymes also involved in protein digestion which contains 1-2 zinc atoms for catalytic activity.
- Delta (Δ)-Aminolevulinic Acid Dehydratase: Heme Synthesis- needed for heme synthesis is zinc dependent. Interestingly, lead when present in the body in high concentrations can replace zinc in the dehydratase and diminishes heme synthesis.
- Superoxide dismutase (SOD1)- an antioxidant found in the cell cytosol requires two atoms of zinc (and two copper) to function. An extracellular form of the enzyme (SOD3) that is also zinc and copper dependent has been characterized and appears to be more sensitive to zinc than is the cytosolic form of the enzyme. Both the cytosolic and extracellular forms of superoxide dismutase serve important antioxidant defense roles in the body by catalyzing the removal of superoxide radicals, O2
- Phospholipase C-this enzyme hydrolyzes the glycerophosphate bond in phospholipids (a structural component of cell membranes!). It requires 3 zinc atoms for catalytic activity.
- Matrix Metalloproteinases-The matrix metalloproteinases are zinc containing endopeptidases (zinc is located in the catalytic site where substrate binds). They generally function in wound healing, degrading components of the extracellular matrix (among other roles) to allow for remodeling of extracellular matrix proteins and tissue repair
- Polymerases, Kinases, Nucleases, Transferases, Phosphorylases, and Transcriptases- Nucleic Acid Synthesis and Cell Replication and Growth Polymerases, kinases, nucleases, transferases, phosphorylases, and transcriptases all require zinc.
- Gene expression- Zinc plays a major structural role in regulating gene transcription by promoting a confirmation change in the shape of the transcription factor protein. You may have heard the term zinc fingers which is often used to indicate the secondary shape (configuration) of the transcription factor proteins when bound to zinc.
In addition to the above roles, zinc helps maintain cell membranes through multiple actions on membrane proteins including direct effects on membrane proteins’ conformation, on protein-to-protein interactions, and on other membrane components
Zinc itself also is believed to stabilize membrane structure by stabilizing phospholipids and thiol (SH) groups in enzymes and membrane proteins that need to be maintained in a reduced state.
Zinc may also stabilize membranes by quenching free radicals as part of metallothionein and by promoting associations between membrane skeletal and cytoskeletal proteins
Additionally, zinc in cells is found bound to tubulin, a protein that makes up the microtubules. Microtubules are thought to act as a framework for structural support of the cell as well as enable movement.
Zinc is also involved with insulin and thus influences carbohydrate metabolism. Zinc is transported into pancreatic b-cells by zinc transporter ZnT8, which also enables uptake into secretory vesicles. Pancreatic b-cells are responsible for insulin production and secretion (Gropper, n.d.).
Zinc can also influence the basal metabolic rate (BMR). A decrease in thyroid hormones and basal metabolic rate has been observed with consumption of a zinc-restricted diet (Gropper, n.d.).
Zinc is also important for taste; it is a component of gustin, a protein involved in taste acuity (Gropper, n.d.).
Cell mediated and humoral immunity are also influenced by zinc. T-cells are critical to immune system function and with zinc deficiency, thymulin activity diminishes and profoundly affects T-cell numbers and functions, and pre-T-cell apoptosis (programmed cell death) (Gropper, n.d.).
Some signs and symptoms of deficiency in adults include anorexia, diarrhea, lethargy, depression, skin rash/ lesions/dermatitis, hypogeusia (blunting of sense of taste), alopecia (some hair loss; remaining hair make take on a reddish hue), vision problems, and impaired immune function, protein synthesis, and wound healing (Gropper, n.d.).
Zinc deficiency can be associated with decreased mobilization of retinol from the liver (even with adequate liver vitamin A stores) as well as decreased plasma retinol-binding protein concentrations (Gropper, n.d.).
An overall deficiency of zinc stores within the body has been implicated in the systemic susceptibility of infection and in the pathogenesis of some cancers (Liu et al., 2011)
Zinc also demonstrates an important role within the lumen of the alimentary canal, as evidenced on the observations that supplementation of oral diets with Zn2+ has beneficial effects on diarrhea and inflammatory conditions of the gastrointestinal tract (Liu et al., 2011). “In gastric mucosa, adequate intracellular stores and luminal content of Zn2+ may regulate integrity of and acid secretion by the gastric glands and enhance protection of the mucosa as a whole against acid-peptic injury (Liu et al., 2011).
Evaluating zinc nutriture is difficult, owing to homeostatic control of body zinc. A variety of indices have been used to assess zinc status, including measurements of zinc in red blood cells, leukocytes, neutrophils, and plasma or serum.
The most common basis for assessment is serum or plasma zinc, with fasting concentrations less than about 70 µg/dL (10 µmol/L) suggesting deficiency. A cutoff of 50 µg/dL, however, may better predict clinical signs of zinc deficiency (Gropper, n.d.). Plasma zinc concentrations range from about 70 to 120 μg/dL (10–18 µmol/L), with plasma containing about 3 mg of zinc. Plasma zinc concentrations decrease after eating, as well as under conditions of infection and trauma
Low fasting plasma zinc concentrations indicate that little zinc is present in the exchangeable zinc pool and may reflect a loss of tissue zinc (especially from the liver). Plasma zinc concentrations, however, must be interpreted with caution because concentrations are influenced by many factors unrelated to zinc depletion, including meals, time of day (diurnal variation), stress, infection, and medications such as steroid therapy. In fact, postprandial (after eating) plasma zinc concentrations have been found to be more sensitive to low dietary zinc intake than fasting plasma zinc concentrations (Gropper, n.d.)..
Metallothionein has also been used to assess zinc status. Concentrations of metallothionein respond to changes in dietary zinc. For example, liver and red blood cell metallothionein concentrations diminish as dietary zinc intake decreases and are thought to reflect zinc status or stores (Gropper, n.d.).
Serum zinc and serum metallothionein concentrations can be used to indicate poor zinc status if both are low. Elevations in serum metallothionein coupled with low serum zinc, however, usually suggest an acute-phase response, and in such conditions these indices are not reliable. Urinary zinc excretion remains fairly constant over a range of intakes and is thought to be a useful marker of status in those with moderate to severe zinc deficiency (Gropper, n.d.)..
Low hair zinc may be associated with chronic intake of dietary zinc in suboptimal amounts; however, the concentration of zinc in hair depends not only on delivery of zinc to the root but also on the rate of hair growth, which is affected by other conditions (including protein status)(Gropper, n.d.).
.Measurement of the activity of zinc-dependent enzymes has also been employed as an index of zinc status. Studies using enzymes as indicators typically have measured carbonic anhydrase or alkaline phosphatase, which “hold” zinc less securely than other zinc metalloenzymes.
Ideally, measurements of activity should be taken before and after zinc supplementation (Gropper, n.d.)..
Supporting deficiency in adults typically requires oral zinc supplementation; doses of 10–20 mg/day are recommended. Although higher doses (often up to 50 mg given two to three times per day) may be prescribed, use of such doses is more likely to impair copper status.
Some population groups—especially older adults, vegetarians, and those with alcoholism and with limited income—have been found to consume less than adequate amounts of zinc.
Alcohol ingestion additionally reduces intestinal zinc absorption and increases urinary zinc excretion.
Additional conditions associated with an increased need for intake include trauma, sickle-cell anemia, and disorders causing malabsorption such as Crohn’s disease, short bowel syndrome, celiac disease, and liver failure, as well as surgical bariatric procedures, especially Roux-en-Y gastric bypass and duodenal switch, used to treat obesity. Diarrhea and intestinal fistulas also substantially increase fecal zinc losses; supplementation with up to 20 mg of zinc/day may be needed under such conditions.
ZINC and COPPER
The detrimental effect of excessive zinc intake on copper absorption is thought to be attributable to zinc’s stimulation of the synthesis of metallothionein, which has a higher affinity for copper than for zinc. With increased intestinal concentrations of metallothionein induced by high zinc levels, ingested copper readily binds to the metallothionein within the enterocyte and becomes “trapped,” preventing its passage into the plasma. The increased risk of copper deficiency precipitated by zinc supplementation led to the Tolerable Upper Intake Level for elemental zinc of 40 mg daily.
Recent reports have begun to explore the mechanisms that regulate cellular homeostasis of Zn2+ in mucosal cells of the gastrointestinal tract (Liu et al., 2011)
There is a relationship to zinc uptake is dependent on intracellular Ca2+ stores.According to Liu et al (2011), baseline conditions, uptake of Zn2+ across the basolateral membrane depends on adequate stores of intracellular calcium ion (Ca2+) . With stimulation by powerful agonists such as forskolin and carbachol, demand for extracellular Zn2+ increases and depends on influx of extracellular Ca2+ .
“In the current set of studies, we find that Ca2+ facilitates optimal uptake of Zn2+ across the cell membrane, implying that it is either a counter-ion in exchange or it is acting as a regulatory second messenger. Membrane proteins that facilitate Zn2+ transport constitute the SLC30A (ZnT) and SLC39A (Zip) gene families” (Liu et al., 2011).
Diminished calcium absorption has been observed with the ingestion of zinc supplements when calcium intake is low (<300 mg/day of calcium). However, calcium absorption appears to be unaffected by zinc when calcium intake is at adequate (recommended) levels.
Cadmium, if present in high concentrations in the body, appears to bind to sites to which zinc would normally bind and thus disrupts normal zinc functions. For example, cadmium can replace zinc in zinc fingers, preventing the fingers from functioning as they would with zinc present.
Zinc is found in foods complexed with nucleic acids and with amino acids that are part of peptides and proteins. The zinc content of foods varies widely.
Very good sources of zinc are red meats (especially organ meats) and seafood (especially oysters and mollusks). Other relatively good animal sources of zinc include poultry, pork, and dairy products. Animal products are thought to provide 40–70% of zinc consumed by most people in the United States.
Whole grains and legumes also provide moderate amounts of zinc.
Cereals, some of which may be fortified, are thought to provide about 30% of the zinc in the U.S. diet. Fruits contain little zinc.
Plant sources, however, not only have lower zinc contents, but zinc from plants is also absorbed to a lesser extent than zinc from animal sources (e.g., meat).
Zinc absorption is enhanced with:
Ligands or chelators including organic acids (like citric acid and picolinic acid) and prostaglandins may bind and promote zinc absorption
Glutathione and products of protein digestion, such as amino acids, serve as ligands (such as sulfur, cysteine, or nitrogen). Interestingly, amino acids serving as ligands help maintain zinc’s solubility in the gastrointestinal tract
Absorption of zinc is also enhanced by an acidic environment. Thus, the use of medication such as antacids, H2 receptor blockers (such as Zantac [ranitidine], Tagamet [cimetidine], or Pepcid [famotidine]), and proton pump blockers (such as Prevacid [lansoprazole] or Prilosec [omeprazole]), which are commonly taken to treat heartburn, gastroesophageal reflux disease, and ulcers, increases gastric and proximal intestinal pH and decreases zinc absorption
Phytic acid found in plant foods, particularly legumes, lentils, nuts, seeds, and whole-grain cereals decrease absorption
Other minerals such as iron and calcium negatively impact absorption
Gropper, Sareen S.; Smith, Jack L.; Carr, Timothy P.. Advanced Nutrition and Human Metabolism (Page 509). Wadsworth Publishing. Kindle Edition.
Liu, J., Kohler, J. E., Blass, A. L., Moncaster, J. A., Mocofanescu, A., Marcus, M. A., . . . Soybel, D. I. (2011). Demand for Zn2+ in acid-secreting gastric mucosa and its requirement for intracellular Ca2+. PLoS ONE, 6(6), e19638. doi:10.1371/journal.pone.0019638
The relationship between thiamine and diabetes mellitus (DM) has been reported in the literature (Luong & Nguyen, 2012). Thiamine acts as a coenzyme for transketolase (Tk) and for the pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase complexes. These enzymes play a fundamental role for intracellular glucose metabolism by increasing Krebs cycle activity (Luong & Nguyen, 2012). Low thiamine has been reported to be decreased by 76% in T1D and 75% in T2D patients, as evidenced by low blood thiamine levels, erythrocyte transketolase activity and high erythrocyte thiamine pyrophosphate (TPP).
Additionally, thiamine transporter protein concentration has been shown to be increased in erythrocyte membranes of T1D and T2D patients. “Therefore, changes in thiamine levels may be masked by an increase in thiamine transporter expression” (Luong & Nguyen, 2012). The low thiamine values in diabetic patients might also be a reduced apo-enzyme level from the disease itself rather than thiamine deficiency (Luong & Nguyen, 2012)
I think it is important to mention, there are four distinct biochemical pathways that have been identified as mechanisms in which intracellular hyperglycemia can promote some of the complications of diabetes (such as vascular damage, renal impairment, neurological damage and endothelial damage in the retina) (Brownlee, 2005). These include: increased flux through the polyol pathway, formation of AGE’s, activation of protein C kinase pathway and increase flux through hexosamine biosynthetic pathway. I will briefly discuss each below (Luong & Nguyen, 2012).
- Polyol pathway- This pathway focuses on the enzyme aldose reductase, which is responsible for reducing toxic aldehydes in the cell to inactive alcohols. But when the glucose concentration is too high in the cell, aldose reductase reduces the glucose to sorbitol. NADPH is used to drive this reaction forward, but it runs the risk of being overconsumed in this process. When there is elevated blood glucose and energy overload in the cell, we start to waste NADPH which is essential for regeneration of GSH. When we are running through this pathway, it can cause a glutathione deficit in the cell, which is why sometimes diabetes is associated with GSH deficiency. By reducing the amount of reduced glutathione, the polyol pathway can increase susceptibility to intracellular oxidative stress (Luong & Nguyen, 2012).
- Intracellular production of AGE precursors. AGE’s are toxic compounds deriving from non-enzymatic glycoxidation reactions of reducing sugars with proteins, which then result as being structurally and functionally compromised. Protein glycation occurs in vivo in physiological conditions as a post-translational modification that takes place slowly and continuously during the life span, driving AGE accumulation in tissues during aging. AGE’s have been associated with age related conditions such as diabetes and insulin resistance. In addition, accumulation of AGE’s is accelerated leading to other conditions (Aragno & Mastrocola, 2017).
- Activation of the protein Kinase C pathway- High levels of fatty acids and hyperglycemia activate DAG, which turns on PKC. This promotes various processes that results in decreased nitric oxide (NO) bioavailability. Reducing NO availability and produces oxidative stress in the nervous and vascular system, and reduce ability to synthesize NO which can increase oxidative stress(neuro and vascular) and reduce the ability to synthesize NO which can increase vasoconstriction, poor blood flow and oxygenation of tissue (Roberts & Porter, 2013).
- Hexosamine pathway– Chronic high blood pressure can upregulate this pathway. Fructose 6-P is transformed to glucosamine 6-P by the enzyme glutamine fructose 6-P amidotransferase (GFAT). Glucosamine then promotes the synthesis of uridine diphosphate-N-acetylhexosamine (UDP-GlcNAc) that then serves as a substrate for N- or O-glycation of numerous proteins (Luo, Wu, Jing, & Yan, 2016). “This posttranslational modification can enhance glucotoxicity by impairing protein function and has been demonstrated to be involved in insulin resistance and pathogenesis of diabetes” (Luo et al., 2016). If transketolase activity is low, it is likely that fructose 6 pathway will go through hexosamine pathway, instead of the pentose phosphate pathway which thiamine is a cofactor.
Diabetics are associated with tissue specific thiamine deficiency. This is often demonstrated by: a marked decrease of plasma thiamine concentration; decreased activity of the thiamine-dependent enzyme of transketolase (TK); decreased levels of TK protein in renal glomeruli linked to a profound increase in renal clearance of thiamine (Thornalley et al., 2007). According to Thornalley et al (2007), diabetics are statically more likely to be more thiamine deficient since they waste it through kidneys making their requirement higher.
Insulin deficiency is also associated with reduced rate of thiamine transport across the intestine. High prevalence of low plasma concentrations is prevalent in patients with T1 and T2 diabetes, associated with thiamine clearance
What all this means?
Transketolase acts as a bridge between PPP and glycolytic pathway requiring B1 as a cofactor. Thiamine deficiency slows down transketolase. With thiamine, the pentose phosphate pathway can take the extra intermediates of the glycolytic pathway until we need to make more energy. When there is thiamine deficiency, we are unable to effectively shunt these intermediates down the pentose phosphate pathway( PPP), we end up with build up of intermediates. When this energetic block occurs, such as in mitochondrial dysfunction, the intermediates are shunted into alternative pathways. These yield inflammatory products, and it is the products of these pathways that are central in the damage caused by diabetes or involved in diabetic complications.
In diabetes, there is an overload of energy, which causes reverse the electron flow which can then increase reactive oxygen species. Decreased availability of thiamine in vascular cells in diabetes exacerbates metabolic dysfunction in hyperglycemia (Thornalley et al., 2007). These yield inflammatory products as indicate above, and it is the products of these pathways that are central in the damage caused by diabetes or involved in diabetic complications.
It is thought that thiamine supplementation is helpful in diabetes. Thiamine supplementation can reduce AGE formation, reduce flow through hexosamine and polyol pathway, reduce protein kinase C activity, inhibits NF-KB activation and normalize markers associated with methylglyoxal and glycation.
High dose supplementation as befothiamine and thiamine hydrochloride possess antioxidant properties, reduces lipid peroxidation, reduces oxidative stress associated with diabetes and activates eNOS (EONutrition, 2019). It may also improve endothelial dysfunction in a hyperglycemic state. In addition, it may improve pain associated with diabetic polyneuropathy and reduce urinary albumin excretion, reducing renal AGE’s and oxidative damage (EONutrition, 2019).
Aragno, M., & Mastrocola, R. (2017). Dietary Sugars and Endogenous Formation of Advanced Glycation Endproducts: Emerging Mechanisms of Disease. Nutrients, 9(4). doi:10.3390/nu9040385
Brownlee, M. (2005). The pathobiology of diabetic complications: a unifying mechanism. Diabetes, 54(6), 1615-1625. doi:10.2337/diabetes.54.6.1615
EONutrition (2019). Retrieved (2020, June 22) from https://www.youtube.com/watch?v=m3DopqTz1Q4&t=801s
Luo, X., Wu, J., Jing, S., & Yan, L. J. (2016). Hyperglycemic Stress and Carbon Stress in Diabetic Glucotoxicity. Aging Dis, 7(1), 90-110. doi:10.14336/ad.2015.0702
Luong, K. V., & Nguyen, L. T. (2012). The impact of thiamine treatment in the diabetes mellitus. J Clin Med Res, 4(3), 153-160. doi:10.4021/jocmr890w
Roberts, A. C., & Porter, K. E. (2013). Cellular and molecular mechanisms of endothelial dysfunction in diabetes. Diab Vasc Dis Res, 10(6), 472-482. doi:10.1177/1479164113500680
Thornalley, P. J., Babaei-Jadidi, R., Al Ali, H., Rabbani, N., Antonysunil, A., Larkin, J., . . . Bodmer, C. W. (2007). High prevalence of low plasma thiamine concentration in diabetes linked to a marker of vascular disease. Diabetologia, 50(10), 2164-2170. doi:10.1007/s00125-007-0771-4
It is no secret that exercise is very important for optimal health. But many people still do not see the connection and it seems to be a low priority for them when it comes to managing their health. However, I realize that many people truly do not understand how important it really is, even from the perspective of glycolytic pathway, so I want to take the time to summarize it here. Exercise is known to stimulate glycogenolysis, especially when it is conducted first thing in the morning after an overnight fast. In fact, I often tell my clients to do their exercise fasted when they want to optimize weight loss. But how does it work?
Before I review that, I want to do a quick summary of biochemistry.
In our muscles, glycogen supplies glucose-6-phosphate for ATP synthesis in the glycolytic pathway. Any enzyme known as glycogen phosphorylase in the muscle is stimulated during exercise by the increase of AMP and by phosphorylation. The phosphorylation is stimulated by calcium released during contraction and by epinephrine, the fight or flight hormone, as well as hypoglycemia during stressful situations or exercise where there is an immediate need for glucose. It is important to understand that liver glycogen stores are principally for the support of blood glucose during fasting or extreme need such as exercise, and the degradative and biosynthetic pathways are regulated principally by changes in the insulin/glucagon ratio and by blood glucose levels. The key point to remember is that muscle glycogenolysis is regulated principally by AMP, which signals a lack of ATP, and by Ca2+ released during contraction. Epinephrine, which is released in response to exercise and other stress situations, also activates skeletal muscle glycogenolysis.
Let’s take a practical look at what happens when someone begins to contract their muscles during exercise. If someone were to immediately begin running as fast as possible, the following cascade would take place.
- Within 3 seconds, muscle cells exhaust stored ATP.
- As exercise continues, this ATP must be regenerated, so the ATP–PCr system kicks in to shoulder most of the load. This lasts for about 10 seconds. And because time is required for ATP to be regenerated, you start to slow down a bit.
- As exercise continues and the ATP–PCr stores are depleted, the glycolytic system will begin to provide most of the energy transfer for ATP regeneration. This lasts for about 90 to 120 seconds or so, depending on the intensity of the exercise. Since the glycolytic system generates ATP more slowly than the ATP–PCr system, again, you have to slow down a bit more.
- If exercise continues beyond this time frame, the oxidative system will start to provide most of the energy transfer for ATP regeneration. And again, because the oxidative systems are slower than the anaerobic systems, the pace must slow again. In fact, if the pace is slow enough, the exercise can last for quite a long time.
There are two main types of exercise: anaerobic exercise and aerobic exercise. Anaerobic exercise is defined as higher-intensity, shorter-duration (less than 2 minutes) activity, whereas aerobic exercise occurs when the exercise is longer than 2 minutes in which the oxidative system must kick in to provide the remaining energy for ATP regeneration. As our initial energy stores can only supply energy for about three seconds, our ATP must be regenerated in large amounts, and quickly, to support this type of exercise.
Short-burst activities such as the following:
- The golf swing
- Field events (shot put, discuss)
- The tennis swing
- The 100-meter sprint
- The baseball swing
Oxidative energy transfer takes place in the mitochondria of our cells and utilizes a combination of muscle glycogen, intramuscular fatty acids, free fatty acids, and amino acids. As the oxidative processes utilize breakdown products from both glycolysis (glucose through to pyruvate) and beta oxidation (fatty acids through to acetyl-coA), energy transfer occurs at a slower rate. However, what this system lacks in speed, it makes up for in ATP regeneration. As a result, oxidative metabolism can support activities including the following:
- 800-meter run
- 2000-meter rowing
- 1500-meter skating
- Cross-country skiing
- Long-distance swimming
Indeed, any activity done at a high intensity for longer than two minutes derives a large percentage of its energy transfer from the oxidative system. There is a “switchover point” at which an activity moves from anaerobic to aerobic, as seen in this interesting comparison.
- 200-meter run: 29% aerobic; 71% anaerobic
- 400-meter run: 43% aerobic; 57% anaerobic
- 800-meter run: 66% aerobic: 34% anaerobic
- 1500-meter run: 84% aerobic; 16% anaerobic
The primary muscle fiber types that contribute to aerobic exercise are the oxidative type I and type IIA fibers. As aerobic exercise is heavily oxygen dependent, training adaptations occur in order to support oxygen transport and delivery in these fibers. Specifically, aerobic exercise can increase the number and size of the blood vessels. This occurs through increased capillarization. Specifically, with aerobic training, there is a greater number of capillaries per unit of muscle. This allows for enhanced delivery of oxygen (fuel) to muscle cells, enhanced removal of CO2 and waste products, and the transfer of heat away from the muscle. In addition to enhanced oxygen delivery, there is an increase in the size and number of mitochondria along with greater myoglobin content within cells. While the greater capillarization leads to more oxygen transport, the greater myoglobin leads to increased muscle oxygen uptake, and the larger and more numerous mitochondria allow for greater oxygen use. Of course, in addition to these adaptations, the enzymes involved with aerobic energy transfer will adapt as well.
Let’s talk a bit about oxygen and the adaptations that occur with regular exercise.
After a full exercise session, or even after a single interval within an entire exercise session, the oxygen deficit that’s accumulated must be paid back. This means that after you’ve stopped exercising and the amount of mechanical work you’re doing is no different than you’d be doing at rest, you still continue to consume more oxygen. This period of increased oxygen consumption and energy demand has been called the period of oxygen debt or EPOC (excess post-exercise oxygen consumption). In essence, after exercise, the amount of oxygen consumed can be elevated for minutes to hours. This is due to the fact that the body must:
- a) metabolize additional nutrients,
- b) replenish the energy stores that have been used up, and
- c) reload the depleted oxygen stores in the muscle and blood.
In addition to these recovery-type activities, the following also contribute to the EPOC:
- Elevated post-exercise body temperature
- Increased activity of the heart and respiratory muscles
- Elevated levels of metabolism-boosting hormones
- Increased conversion of energy transfer products such as lactate into other substrates
- Increased protein synthesis
- Recovery of muscles stressed and damaged with the activity
It is important to note, however, that the energy systems do not work independently from one another. During various types of exercise, from aerobic to anaerobic, all three energy systems are activated. However, the extent to which they are activated, and the amount of ATP they regenerate relative to the total ATP regeneration required, determines the description of the activity. For example, during short-burst activity, the ATP–PCr system is most important. When immediate and explosive movement is desired, the brain initiates the contraction with a signal that’s passed along the nerves to the muscles. The muscles then contract, using ATP and depleting these immediate energy stores within a second or two. In order for the muscles to continue to contract, the resulting ADP and P must be regenerated to ATP.
Adaptations to Exercise.
In response to regular exercise training, whether anaerobic or aerobic, certain changes occur in the muscle. These changes improve the body’s ability to respond to similar exercise challenges in the future. Each of these processes is regulated by protein synthetic mechanisms initiated within our genetic material (our DNA). Cellular communication through hormones is intimately involved in this process. The hormone insulin, in the presence of adequate nutrient availability, encourages the stimulation of protein synthesis and a positive nitrogen balance. Insulin availability is greatest during well-fed conditions and during periods of energy surplus. Protein and amino acid intake is key here as protein-containing meals stimulate a positive protein status. In addition, hormones like testosterone and growth hormone have a stimulatory effect on muscle adaptation.
On the other hand, the counter-regulatory hormones such as glucagon, catecholamines, and glucocorticoids have a contradictory effect, promoting protein breakdown and a negative nitrogen balance. These hormones are released in large numbers during periods of fasting or energy deficit
Protein synthesis and exercise adaptation are also affected by:
- The amount of mRNA in our cells
- Ribosomal number
- Ribosomal activity
- Amino acid availability
- The hormonal environment
- Our native genetic code
Interestingly, even the process of recovering and adapting to our exercise training demands is metabolically costly. As proteins are degraded and amino acids re-synthesized into proteins, this process of protein turnover builds more functionally adapted enzymes, contractile units, etc. And this process accounts for between 10% and 25% of resting energy expenditure. Therefore, as you can see, not only does exercise increase total daily energy expenditure during the activity, it also increases post-exercise expenditure through two mechanisms. Energy expenditure is increased due to both the oxygen debt being paid back and to the increased protein turnover and synthesis just described.
Adaptations of anerobic exercise such as weight training and sprint training:
- muscle fibers both increase in size and in myofibrillar number
- mitochondrial size and number
- increases in myoglobin number
- increases in intracellular storage capacity and availability (such as stored glycogen)
- increases in intracellular glycogen storage can also contribute to muscle hypertrophy
- In addition to changes in muscle cross-sectional area, anaerobic exercise can enhance the activity of ATP–PCr system enzymes (creatine kinase, myokinase) and the glycolytic system enzymes (glycogen phosphorylase, phosphofructokinase).
These changes help to increase the rate of energy transfer within the muscle, allowing for more rapid responses to energy demands in the future.
Adaptations to aerobic exercise such as jogging, steady state cardio or swimming:
Please note, this type of lower-intensity, longer-duration activity primarily influences muscle quality (as opposed to muscle size).
- Enhancement of oxidative or mitochondrial enzyme activity
- Increase in intramuscular glycogen and triglyceride content
- Increase in blood volume due to increase uptake and delivery of aerobic activity- due to increase in red blood cell content and the oxygen-carry capacity of the body.
- Capillary density of trained muscles increases- meaning there will be a great number of capillaries per muscle fiber
- With this lengthened border between blood vessels and muscle fibers, oxygen delivery, carbon dioxide removal, waste removal, fuel delivery to muscle, and the transfer of heat are all amplified.
- Beyond this, the myoglobin content of skeletal muscles will increase, improving oxygen delivery across muscle cells
- Finally, the number and size of mitochondria are increased with aerobic activity of high enough intensity. This promotes greater oxygen utilization through the process of pyruvate, fatty acid, and ketone utilization through the Krebs cycle and electron transport chain
Additional benefits of both aerobic and anaerobic exercise training include:
- The attenuation of sympathetic nervous system activity.In essence, “stress” to the body with exercise is minimized over time, and therefore greater workloads are required to promote the same amount of adaptation.
- Greater insulin sensitivity.With exercise training, the body responds to carbohydrate intake with less insulin release, allowing insulin to act in carbohydrate update and protein synthesis without preventing fat loss/stimulating fat gain.
- Improved fatty acid uptake and transport.Another positive response to exercise training is that fats can be more easily mobilized from adipose tissue, transported, taken up, and broken down.
- Less lactate produced per intensity.At every intensity, less lactate will be produced. This is due to greater aerobic production of ATP at every intensity, lower catecholamine response, reduced carbohydrate metabolism, and changes in the isoenzymes of lactate dehydrogenase to forms that favor the conversion of lactate to pyruvate.
- More lactate removed per unit of intensity.At every intensity, more lactate will be removed. Increased rates of lactate removal are due to increased blood flow to the liver and enhanced uptake of lactate by cardiac and skeletal muscles.
- Better lactate tolerance.With training at the highest intensities, the body can better deal with high acid conditions and high levels of lactate. This means higher intensities can be achieved and sustained for short periods of time.
sympathetic nervous system: One division of the autonomic nervous system that is always active and provides sympathetic tone. Its activity increases during times of bodily stress.
So, what qualifies as “intense exercise”? Resistance training (strength training), interval training(through activities such as running, climbing, cycling, and rowing), circuit training, rope jumping, running hills, squat thrusts, plyometrics, explosive medicine ball work, explosive kettlebell exercises, and strongman activities are all high-intensity activities.
Basically, high-intensity activity includes any physically demanding task that:
- a) incorporates many muscle groups, and
- b) is done near your maximum heart rate.
The high-intensity activities listed above require a maximum of muscle activity, which leads to high amounts of cellular stress and the need for muscle adaptation. It’s this muscle stress and adaptation that brings about the maximum number of benefits, including increased protein turnover, muscle preservation and building, a high energy cost, and even cardiovascular benefits.
However, as important as exercise is to this process, nutrition is equally critical.
Firstly, nutritional status can impact energy transfer. Therefore, a good nutrition program will help facilitate top performance of each of the energy systems: ATP–PCr, glycolysis, and oxidative phosphorylation. Both macronutrients and micronutrients are important here.
A sub-optimal nutritional intake can reduce enzyme efficiency (due to deficiencies of co-enzymes and co-factors) and lead to substrate deficiencies. And this means poor exercise performance and fewer calories burned both at rest and during exercise. So much for the metabolic and muscle preserving and building benefits of exercise. In addition, with an inadequate intake of dietary protein and fat, amino acid availability and the ratio of anabolic to catabolic hormones can be compromised. This can lead to an inability to build and preserve muscle mass, even in the face of a solid exercise program.
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Having worked in the fitness industry for over 15 years and helping people with their weight loss goals, I always wondered what role exercise had on inflammation and aging. In obesity, various mechanisms are thought to contribute to a low- grade inflammation within the fat tissue affecting the development of several secondary diseases of aging such as metabolic syndrome, insulin resistance (IR), diabetes, arterial hypertension, and autoimmune diseases (Schmidt et al., 2015). Most importantly, exercise is demonstrating to help modulate the inflammatory processes associated with aging (inflammaging). Two to four- fold elevations in circulating levels of pro-inflammatory cytokines such as IL-6, TNF-a, and acute phase proteins such as CRP and serum amyloid A (SAA) are typical in the elderly when compared to the young, in the absence of chronic disease. Significant declines in immune function with aging promote inflammation, which can increase the prevalence of conditions associated with “inflammaging” such as hypertension, CV disease, and neurodegeneration. Aging is also associated in increases in circulating levels of reactive oxygen specie (ROS), decline in antioxidant capacity and increase in oxidative stress (Woods, Wilund, Martin, & Kistler, 2012). “While transient inflammation is necessary for recovery from injury and infection, it has been hypothesized that the excessive inflammation in aging may also be caused by an exaggerated acute-phase response that may be a cause or consequence of a delayed recovery from an insult that promotes inflammation” (Woods et al., 2012). This is often seen in failure to completely resolve an immune response or can often been seen in an exaggerated immune response and impaired clearance of the immune mediators.
Exercise has a strong influence on the levels of pro-inflammatory cytokines (Gleeson et al., 2011). In fact there is a strong relationship to BMI that may indicate that the decrease in inflammatory molecules may be related to decrease in visceral fat. Additionally, physical activity may further mitigate inflammation by improving endothelial function, increasing insulin sensitivity, enhancing liver health and increasing blood vessel growth and blood flow.
Various mechanisms are involved in exercise’s role in lowering inflammation, some of them are listed below:
- Reduction in visceral mass-as mentioned early, a reduction in visceral mass has an indirect effect of being able to decrease inflammation, since accumulation of fat in the omentum, liver and muscles, as well as the expansion of adipose tissue, results in enhanced production of certain inflammatory mediators. Therefore loss of visceral fat can result in reduction in inflammation (Gleeson et al., 2011).
- Release of IL-6 from working muscles-A fall in muscle glycogen content with exercise signals the muscles to secrete IL-6 (a pro-inflammatory cytokine), which stays high during the duration of exercise. However, this also initiates a rise in anti-inflammatory cytokines IL-10 and IL-1RA to minimize the effects on the tissue. Also, it was interesting that you really need 2.5 hours or more of strenuous exercise to get a significant elevation of IL-6, which may partially explain why marathon runners may have suppressed immune systems (Gleeson et al., 2011).
- Increased levels of cortisol and adrenaline-IL-6 stimulates the release of cortisol, which is smaller doses, can have anti-inflammatory effects. It should be pointed out that too much cortisol secretion from the adrenal glands can create a chronic state of inflammation as well, so this could also be a dose dependent phenomenon (Gleeson et al., 2011).
- Reduction in oxidative stress-Regular exercise can reduce oxidative stress by up-regulating endogenous anti-oxidant defense systems, mitigating the damage from overproduction of oxidants such as nitric oxide, peroxynitrate and hydroxyl radicals during aging (Woods et al., 2012
- Resistance training can reduce TNF–a-Muscle protein synthesis was inversely related to TNF-a as demonstrated in the effects of TNF-a genes after 3 months of resistnace training (Woods et al., 2012).
- Vagus nerve stimulation– Stimulation of the parasympathetic nervous system via the vagus nerve can inhibit pro-inflammatory cytokine production and protects against systemic inflammation (Woods et al., 2012). “hey referred to this pathway as the “cholinergic anti-inflammatory pathway,” and described it as a central homeostatic mechanism by which the sympathetic division of the autonomic nervous system stimulates the inflammatory response through the release of epinephrine and norepinephrine, while the parasympathetic nervous system works reciprocally to suppress this release of proinflammatory cytokine” (Woods et al., 2012). This is often evidenced by a decrease in heart rate recovery (HRR) and heart rate variability (HRV) since one of the primary functions of the vagus nerve is to control heart rate (Woods et al., 2012).
- Activation of HPA-axis– Exercise can activate the HPA axis and sympathetic nervous system. This can be due to cortisol’s potent anti-inflammatory effects and catecholamines that can inhibit pro-inflammatory cytokines (Woods et al., 2012)..
“In summary, exercise training is known to have beneficial effects across a broad spectrum of organ systems and its anti-inflammatory actions are complicated by the intricate interplay among organs and cytokines” (Woods et al., 2012). Exercise prescriptions are definitely a necessary element in any protocol that involves optimizing health, reducing inflammation and slowing down inflammatory diseases of stress and aging such what this patient is experiencing.
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Gleeson, M., Bishop, N. C., Stensel, D. J., Lindley, M. R., Mastana, S. S., & Nimmo, M. A. (2011). The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol, 11(9), 607-615. doi:10.1038/nri3041
Part 2 of 2: Inflammation and Exercise: friend or foe? (2011, August 25). Retrieved 2018, May 2 from https://inscientioveritas.org/inflammation-and-exercise/ (Links to an external site.) (Links to an external site.)
Schmidt, F. M., Weschenfelder, J., Sander, C., Minkwitz, J., Thormann, J., Chittka, T., . . . Himmerich, H. (2015). Inflammatory cytokines in general and central obesity and modulating effects of physical activity. PLoS ONE, 10(3), e0121971. doi:10.1371/journal.pone.0121971
Woods, J. A., Wilund, K. R., Martin, S. A., & Kistler, B. M. (2012). Exercise, inflammation and aging. Aging Dis, 3(1), 130-140.
As a fitness instructor, I can really relate to this module. I have been teaching fitness for over 10 years, and have taught all levels of classes from basic cardio classes, HIIT, indoor cycle, and strength classes. In fact, my favorite class I teach is metabolic conditioning, that consists of both higher impact cardio intervals and full body weight training. Due to my extensive experience in the fitness industry, I am a bit biased and believe that all modes of exercise are important for brain health. This includes traditional cardio, interval training and weight training.
Exercise is a promising strategy for combating cognitive decline. According to a study by Nagamatsu et al (2012), both aerobic training and resistance training enhance cognitive performance and functional plasticity in healthy community-dwelling seniors and those with mild cognitive impairment (Nagamatsu, Handy, Hsu, Voss, & Liu-Ambrose, 2012). According to Lucas et al (2015), regular exercise promotes angiogenesis, neurogenesis and synaptic plasticity. This can translate into more “efficient cerebral perfusion and metabolism, neural and vascular adaptation that contribute to the maintenance of cognitive function” (Lucas, Cotter, Brassard, & Bailey, 2015). Exercise affects all the factors and interactions involved in the regulation of cerebrovascular health, such as brain and metabolic neuronal activity, blood pressure, partial pressure of arterial carbon dioxide, cardiac output and sympathetic nervous activity (Lucas et al., 2015). “The increase in vascular NO bioavailability is considered as a key factor in the maintenance of cerebrovascular function and optimal regulation of CBF (cerebral blood flow)” (Lucas et al., 2015). Exercise can help memory and thinking both directly and indirectly. For example, according to Herting et. al (2016), higher-fit children show better performance on tasks of executive functions, such as attention, compared to low-fit children (Herting, Keenan, & Nagel, 2016) The benefits of exercise come from its ability to reduce insulin resistance, reduce inflammation and stimulate the release of growth factors, which can affect the health of brain cells, the growth of new blood vessels in the brain and angiogenesis of new brain cells (Godman, 2014). Indirectly, exercise can improve mood, sleep, reduce stress and anxiety, all contributors of poor brain health which can lead to cognitive impairment. “Many studies have suggested that the parts of the brain that control thinking and memory (the prefrontal cortex and medial temporal cortex) have greater volume in people who exercise versus people who don’t” (Godman, 2014).
Is it more valuable to the brain to do traditional “cardio” work versus resistance training, and why?
According to Nokia, aerobic exercise can enhance adult hippocampal neurogenesis (AHN). “Adult hippocampal neurogenesis (AHN) is a continuous process through which cells proliferate in the subgranular zone of the dentate gyrus, mature into granule cells and, ultimately, become incorporated into hippocampal neuronal networks “ (Nokia et al., 2016). The increase in AHC is considered to be mediated by an upregulation of BDNF and IGF-1. Compared to a sedentary lifestyle, aerobic exercise had the greatest effect on AHN, whereas HIIT has less effect and there was no effect from resistance training (Nokia et al., 2016). However, there are other changes in the brain promoted by exercise, and that includes changes in the hippocampus and also adult neurogenesis in the subventricular zone, as well as the hypothalamus (Nokia et al., 2016). This suggests the neurogenic effects of exercise occur throughout the brain. According to Herting et. al (2016), aerobic exercise also can lead to better cognition and greater gray matter density in regions responsible for cognitive function, leading to greater thickness and volumes in frontal and parietal regions (Herting et al., 2016).
Even though aerobic exercise promotes the most AHN, this does not mean that resistance training is not beneficial for the brain. In fact, a study published in 2012 indicates that resistance training promotes cognitive and functional brain plasticity with people who are already diagnosed with mild cognitive impairment or at risk for dementia. In the 6 month RCT trial by Nagamatsu et. al, six months of twice-weekly resistance training improved selective attention/conflict resolution, associative memory, and regional patterns of functional brain plasticity (Nagamatsu et al., 2012). This provides some evidence that resistance training can benefit multiple areas of in those already at risk for dementia. Aerobic training demonstrated improved selective attention/cognitive resolution in older women with mild cognitive impairment, whereas the resistance training improved associative memory performance, “co-occuring with positive functional changes in hemodynamic activity in regions involved in the memorization of associations” (Nagamatsu et al., 2012).
If you were to design the ultimate brain-based exercise program what would it look like?
An ideal program would consist of both aerobic and resistance exercise in a combinational format. In fact, an article published in 2018 by Northey et al indicates that exercise that is combined with resistance and cardio can boost brain power of people over 50. This study consisted of a large meta-analysis which includes a large number of studies without imposing a limit on publication date or exercise mode. “This study confirms previous suggestions that resistance training may play an important role in improving cognitive function in older adults” (Northey, Cherbuin, Pumpa, Smee, & Rattray, 2018). Although this does not show that resistance training is better than other modes of exercise, it does suggest that this type of training has particularly pronounced effects on these domains of cognitive function. In addition, this review also demonstrated that multicomponent training (cardio and weights combined) can benefit cognitive function in people over age 50. “Our meta-analysis provides positive evidence for the prescription of both aerobic and resistance training (ie, multicomponent training), in accordance with exercise recommendations, for this age group to specifically improve cognitive functions” (Northey et al., 2018). This confirms what I have suspected and seen anecdotally myself in my classes: combinational classes that utilize both cardio and weights seem to be the most effective on all fronts of health, and that includes cognitive health as well.
There are many types of exercise protocols/prescriptions. The one that I use often is called Metabolic Training. It consists of steady state cardio (typically in aerobic or dance format) with some weight training in either Tabata or some type of timed format. I typically use Rest-Based Training (RBT), which has become popular through one of my mentors Jade Teta. His philosophy is to “push till you can’t, rest till you can”. According to Teta (2017):
RBT is a system that makes rest, not work, the primary goal of the workout. It allows participants to take a rest for as long as necessary. Rest actually becomes a tool for increasing intensity, because exercisers can strategically use it to work harder than they could without rest. It also provides a buffer against overexertion, making even high-intensity workouts safe. In RBT, the protocol adapts to the individual rather than forcing the individual to adjust to it.
The ability for the participant to self-regulate gives them autonomy and more likely to develop and maintain innate motivation (Teta, 2017). “When exercisers have control over when to rest and for how long, work volume can increase while safety is maintained” (Teta, 2017). RBT gives the participant full control of their intensity and gives them ownership to the exercise so that “not only work harder but also become more aware of their physiology and more engaged in their programs” (Teta, 2017). I like this, since half the battle I encounter is keeping my clients motivated and committed to their exercise routine. No matter how effective the prescription is, if it is not maintained, benefits are diminished greatly.
I also like to use a format called “Tabata”. In Tabata, we work hard for 20s and rest for 10 seconds, and continue that pattern for a total of 8 rounds. I mix up strength training with cardio training within a Tabata circuit. It comes out to 4 minutes per set. I often superset two different exercises, often times one strength and one cardio, so they are only doing 4 sets instead of 8. The possibilities with Tabata are endless and we have a lot of fun with it! There are other protocols used by trainers as well, but I have found that the higher duration intervals are not perceived as enjoyable as the lower duration. “Protocols with 120s high-intensity intervals are rated as being less enjoyable than protocols with 30s or 60s high-intensity intervals” (Heisz et al., 2016). According to Heiz, this reduced enjoyment of the more strenuous protocols may be related to the individual’s ability to complete the exercise, or their competence. I have found the Tabata to elicit the most favorable feeling of competence with my participants, especially when the intensities were higher. “Alternatively, the accumulated fatigue or physical stress from chronically performing a strenuous exercise may actually increase negative feelings and reduce enjoyment for the exercise over time” (Heisz et al., 2016). I have taught to all different fitness levels. In my morning gym classes, I typically have younger moms and retired folks attending. The class I teach in my neighborhood clubhouse consists of an age group of 50-60, and they also love Tabata and metabolic conditioning. The duration of the exercise never exceeds 30 minutes, although I have even recommended 15-minute metabolic training when time is constrained.
I have to mention that care must be taken to address the individual variation to exercise training. “Although aerobic exercise is, on average, beneficial for health, its effects vary between individuals, presumably as a result of considerable genetic variance” (Nokia et al., 2016). For some, aerobic training provides substantial gain in maximal aerobic capacity (V˙ O2 max) and metabolic health, whereas for others the same amount of training results in little or even negative change. In fact, there are individual differences in the BDNF gene that has been shown to mediate the effect of exercise and brain cognition and how exercise affects brain and behavior (Herting et al., 2016). “The secretion and intracellular trafficking of BDNF is altered by a common functional single nucleotide polymorphism (SNP) within the BDNF gene, known as the val66met” (Herting et al., 2016). In fact, AHN is highest in animals born with a tendency for a higher response to exercise training and that engage in a large amount of voluntary aerobic activity.
Here is a sample weekly workout program for brain health for someone who responds well to the types of training selected (keeping in mind each individual’s prescription will vary based on their genetics):
Sunday-rest and recovery (gentle walk, yoga, tai chi)
Monday- 20-30 minutes Metabolic Training
Tuesday-rest and recovery
Wendesday-20-30 minutes rest and recovery (gentle walk, yoga, tai chi)
Thursday-30-45 minute steady state cardio (optional)
Friday- 15-30 minutes Metabolic Training
Saturday-choose from Metabolic Conditioning or steady state cardio or rest and recovery (based on biofeedback from the training days earlier in the week)
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BMJ (n.d.) Aerobic and Resistance exercise combo can boost brain power of over 50’s. Retrieved (2018, October 8) from https://www.bmj.com/company/newsroom/aerobic-and-resistance-exercise-combo-can-boost-brain-power-of-over-50s/
Boutcher, S. H. (2011). High-intensity intermittent exercise and fat loss. J Obes, 2011, 868305. doi:10.1155/2011/868305
Foster, C., Farland, C. V., Guidotti, F., Harbin, M., Roberts, B., Schuette, J., . . . Porcari, J. P. (2015). The Effects of High Intensity Interval Training vs Steady State Training on Aerobic and Anaerobic Capacity. J Sports Sci Med, 14(4), 747-755.
Herting, M. M., Keenan, M. F., & Nagel, B. J. (2016). Aerobic Fitness Linked to Cortical Brain Development in Adolescent Males: Preliminary Findings Suggest a Possible Role of BDNF Genotype. Front Hum Neurosci, 10, 327. doi:10.3389/fnhum.2016.00327
Lucas, S. J., Cotter, J. D., Brassard, P., & Bailey, D. M. (2015). High-intensity interval exercise and cerebrovascular health: curiosity, cause, and consequence. J Cereb Blood Flow Metab, 35(6), 902-911. doi:10.1038/jcbfm.2015.49
Nagamatsu, L. S., Handy, T. C., Hsu, C. L., Voss, M., & Liu-Ambrose, T. (2012). Resistance training promotes cognitive and functional brain plasticity in seniors with probable mild cognitive impairment. Arch Intern Med, 172(8), 666-668. doi:10.1001/archinternmed.2012.379
Nokia, M. S., Lensu, S., Ahtiainen, J. P., Johansson, P. P., Koch, L. G., Britton, S. L., & Kainulainen, H. (2016). Physical exercise increases adult hippocampal neurogenesis in male rats provided it is aerobic and sustained. J Physiol, 594(7), 1855-1873. doi:10.1113/jp271552
Northey, J. M., Cherbuin, N., Pumpa, K. L., Smee, D. J., & Rattray, B. (2018). Exercise interventions for cognitive function in adults older than 50: a systematic review with meta-analysis. Br J Sports Med, 52(3), 154-160. doi:10.1136/bjsports-2016-096587
Teta, J. (2011). Rest-Based Training. Retrieved (2018, October 8) from http://www.ideafit.com/fitness-library/rest-based-training