How to support detoxification and healthy methylation processes with dietary supplements
The body possesses a very sophisticated system for neutralizing and eliminating toxins. Harmful substances come at us in many ways from exposure to harmful chemicals in food, water and air pollution. There are ways we can enhance our detoxification pathways. Learn how from this authoritative article from our friends at Protocol for Life Balance.
—Dr. Ronald Hoffman
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Our body possesses a very sophisticated and efficient endogenous detoxification system. A multitude of detoxification processes are working simultaneously, day in and day out, to maintain the body’s homeostasis. This equilibrium is obtained by getting rid of xenobiotics (environmental foreign elements entering the body) and by eliminating the normal waste created by our own bodily functions, mainly through the liver, kidneys, the gastrointestinal tract, as well as through respiration and perspiration. It would be impossible to review in one article all of the body’s detoxification systems, but we will explore some detoxification processes and how some dietary supplements can support the detoxification systems of the body.*
Throughout the article we will mention several detoxification processes, including free radical scavenging, phase I & II, and methylation.
Free radical scavenging refers to the ability to trap destructive free radicals generated within the body during normal metabolic processes, including those generated by immune system activity. While the generation of free radicals is an important normal function of the body, in some circumstances, an overproduction of free radicals can be deleterious; hence the need for free radical scavengers that can be either produced within the body or ingested as nutrients through foods or supplements.
“Phase I & II detoxification” refers to two phases of detoxification that take place in the liver; the ultimate goal is to facilitate the biotransformation of xenobiotics and some compounds generated by the body, such as steroid hormones, into inactivated forms that are easily eliminated in the bile and urine.
Phase I refers to the first step in this metabolic biotransformation of fat-soluble compounds into inactivated water-soluble excretable metabolites. Phase I is mediated by a family of enzymes known as cytochrome P450s (CYP) and other enzymes in charge of the hydroxylation and reduction of molecules that need to be discarded by the body. Phase II refers to the biotransformation facilitated by many liver enzymes such as UDP glucuronosyl transferases, glutathione S-transferases, amino acid transferases, N-acetyl transferases, and methyl transferases. These enzymes modify the chemical structure of substances present in the liver into a chemical form that is easily eliminated by the body. The body possesses other detoxification tools, including being able to modulate the expression of genes in charge of the production of detoxification proteins. Detoxification also occurs through protein carriers dedicated to eliminating heavy metals.(1)
Methylation is a biochemical process that occurs in all cells of the body. It refers to the addition of a methyl group (a small molecule made of one atom of carbon and three atoms of hydrogen) to an organic compound (protein, DNA, hormones, vitamins, neurotransmitters, etc.). The process of methylation aids in the activation of certain vitamins, energy production, detoxification pathways, and more.
Methylation is notably involved in detoxification via the one-carbon metabolism pathway, which is a biological cycle that occurs within cells and is necessary for proper DNA methylation as well as for recycling homocysteine, a compound known to be linked to increased cardiovascular risk.(2) To function properly, this cycle needs dietary sources of vitamins B12, B6, B2, folate, betaine, choline, and methionine. Insufficient intake of these nutrients may result in a dysregulated one-carbon metabolism pathway, which may result in decreased S-adenosyl methionine (SAMe) production and DNA methylation, as well as increased homocysteine levels.(2)
B-vitamins have other function outside of the one-carbon metabolism pathway. They are required as co‐enzymes for numerous biochemical reactions that are essential to cellular function and energy production, notably at the mitochondrial level.* Some of the systems in which B vitamins function can be summarized as follows: riboflavin is important for the cellular respiratory chain, energy metabolism, metabolism of neurotransmitters; vitamins B6 and B12 are involved in cellular energy production, glutathione and nucleotides biosynthesis; and folate is essential for the biosynthesis of nucleotides and S‐adenosylmethionine (SAMe).* While it is not a B-vitamin, betaine is an essential component of the one-carbon metabolism pathway.* As a methyl group donor, it helps recycle homocysteine and supports healthy liver function.* It also helps to maintain intercellular osmolarity and protects proteins from denaturation.*
Dietary supplements containing the micronutrients involved in the one-carbon metabolism pathway can help support healthy methylation, resulting in the production of SAMe and the proper recycling of homocysteine.*
Other supplements can support other detoxification pathways – for example calcium-D-glucarate (calcium salt of D-glucaric acid) is a substance produced naturally in small amounts by the body. Glucaric acid is also found in many fruits and vegetables with the highest concentrations to be found in oranges, apples, grapefruit, and cruciferous vegetables. Calcium-D-glucarate’s detoxifying properties are attributed to its ability to increase glucuronidation and excretion of potentially toxic compounds.* Glucuronidation, also known as conjugation, is a metabolic biotransformation that takes place during phase II detoxification in the liver. Chemicals, steroid hormones, and other fat-soluble xenobiotics are conjugated with glucuronic acid which make them easier to discard via urine or through the biliary tract to be eliminated in feces. Beta-glucuronidase is an enzyme present in the colonic microflora that can reverse the glucuronidation of these potential toxins, making it possible for them to be reabsorbed by the intestine rather than being discarded in feces. By blocking the action of beta-glucuronidase, calcium-D-glucarate helps to increase the elimination of conjugated xenobiotic compounds and to decrease the activity of harmful substances that are most active in their deconjugated state.*(5)
Another compound involved in detoxification is glutathione (gamma-l-glutamyl-l-cysteinyl-glycine, a.k.a, GSH), which is found in virtually all cells.(6) It plays a critical role in the body’s defense system against oxidative stress by acting directly to neutralize free radicals, as well as by maintaining the activity of vitamins C and E.* Glutathione is also required for proper detoxification of metabolic waste products and is essential for healthy immune system function.*(7) Glutathione is also present in mitochondria where it regulates energy production and is critical to the control of oxidative stress within the mitochondria matrix.*(6)
While glutathione is an important compound for normal cellular function, observational studies have shown that both blood levels and mitochondrial levels of glutathione decrease with age, even in healthy populations.(6, 8) Glutathione is present in many foodstuff including fresh fruits/vegetables, mushrooms, and raw meats; however, cooking and processing food considerably reduces the amount of glutathione available for absorption when this type of food is eaten.(9, 10) Furthermore, once ingested, glutathione is known to be relatively poorly absorbed.(11) Therefore, using a supplemental source of glutathione in addition to regular food sources is a great way to replenish its body stores and compensate age-related depletion.* Glutathione can also have other health supporting benefits, notably on skin.*(12)Indeed, in a randomized, double-blind, placebo-controlled study healthy women receiving 250 mg/d glutathione or placebo for 12 weeks experienced significantly better skin appearance (melanin index, wrinkle formation as measured by Visioscan®) in the glutathione group than in the placebo.*(12)
Alpha-lipoic acid (5-(1,2-dithiolan3-yl) pentanoic acid) is another compound involved in the regulation of oxidative stress at the cellular level.*(13) It is found naturally in mitochondria where it acts as the coenzyme for pyruvate dehydrogenase and α-ketoglutarate dehydrogenase.* It can also help regenerate glutathione and vitamins C and E.*(14) Pre-clinical animal studies suggest that alpha-lipoic acid supplementation may help to reverse age-associated decline in mitochondrial enzymes and may lower the increased risk of oxidative damage that occurs during the aging process.* Other animal studies have found that alpha-lipoic acid protects the heart mitochondria against the effects of aging.* These animal studies suggest that alpha-lipoic acid supplementation may support healthy aging.*(14)
Humans can synthesize alpha-lipoic acid from fatty acids and cysteine, but only in very small amounts. Therefore, to maintain body stores, it needs to be obtained from the diet. Dietary sources are found in both animal and plant materials, notably in red meat and organ meats, such as liver, heart and kidney. The most abundant plant sources are spinach, broccoli, tomatoes, Brussels sprouts, potatoes, peas and rice bran. Some studies suggest that alpha-lipoic acid from dietary supplements has better bioavailability compared to food since it is not bound to proteins. It has also been suggested that the food matrix reduces alpha-lipoic acid bioavailability. Therefore, it is recommended that alpha-lipoic acid supplements be taken 30 minutes before, or 2 hours after eating.(15)
Protocol For Life Balance® is a brand of affordable high-quality dietary supplements offering a wide range of supplements supporting detoxification processes that include ingredients such as B-vitamins, betaine, calcium-D-glucarate, glutathione, and alpha-lipoic acid.* Notable products in this category are, Methyl Action, Calcium D-Glucarate, Glutathione (500 mg reduced form glutathione plus 50 mg alpha-lipoic acid per capsule). Consulting a healthcare professional for a customized detoxification program is recommended to optimize general health and get rid of potentially deleterious xenobiotics and other waste generated within the body.*
References:
1. Hodges RE, Minich DM. Modulation of metabolic detoxification pathways using foods and food-derived components: a scientific review with clinical application. Journal of nutrition and metabolism. 2015;2015.
2. Anderson OS, Sant KE, Dolinoy DC. Nutrition and epigenetics: an interplay of dietary methyl donors, one-carbonmetabolism and DNA methylation. The Journal of nutritional biochemistry. 2012.
3. Coppedè F, Denaro M, Tannorella P, Migliore L. Increased MTHFR promoter methylation in mothers of Down syndrome individuals. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 2016;787:1-6.
4. Moll S, Varga EA. Homocysteine and MTHFR mutations. Circulation. 2015;132(1):e6-e9.
5. Review, States U, Aug;7(4):336-9. AMR. Calcium-D-glucarate. Alternative medicine review : a journal of clinical therapeutic. 2002;7(4):336-9.
6. Marí M, de Gregorio E, de Dios C, Roca-Agujetas V, Cucarull B, Tutusaus A, et al. Mitochondrial glutathione: recent insights and role in disease. Antioxidants. 2020;9(10):909.
7. Jones D. The health dividend of glutathione. The Natural Medicine Journal. 2011.
8. Lang CA, Naryshkin S, Schneider DL, Mills BJ, Lindeman RD. Low blood glutathione levels in healthy aging adults. The Journal of laboratory and clinical medicine. 1992;120(5):720-5.
9. Kalaras MD, Richie JP, Calcagnotto A, Beelman RB. Mushrooms: A rich source of the antioxidants ergothioneine and glutathione. Food chemistry. 2017;233:429-33.
10. Wierzbicka GT, Hagen TM, Tones DP. Glutathione in food. Journal of Food Composition and Analysis. 1989;2(4):327-37.
11. Park EY, Shimura N, Konishi T, Sauchi Y, Wada S, Aoi W, et al. Increase in the Protein-Bound Form of Glutathione in Human Blood after the Oral Administration of Glutathione. Journal of agricultural and food chemistry. 2014;62(26):6183-9.
12. Weschawalit S, Thongthip S, Phutrakool P, Asawanonda P. Glutathione and its antiaging and antimelanogenic effects. Clinical, cosmetic and investigational dermatology. 2017;10:147.
13. Bilska A, Wlodek L. Lipoic acid – the drug of the future? Pharmacol Rep. 2005;57(5):570-7.
14. Singh U, Jialal I. Alpha-lipoic acid supplementation and diabetes. Nutrition Reviews. 2008;66(11):646-57.
15. Goraca A, Huk-Kolega H, Piechota A. Lipoic acid – biological activity and therapeuticpotential. Pharmacological Reports. 2011;63(849):849-58.
* These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.