Nutrition Support of Metabolic Detoxification

The detoxification or “biotransformation” of toxic compounds into something less harmful and more excretable requires several nutrients and plant-based compounds called phytochemicals or phytonutrients. Compounds that require detoxification include pharmaceuticals, hormones, bilirubin, heavy metals, and environmental pollutants such as pesticides and phthalates.

This metabolic detoxification occurs in steps and phases that depend heavily on amino acids, antioxidants, vitamins, minerals, and phytonutrients. Specific steps include phase 1 cytochrome P450 enzymes, phase 1 hydroxylation and reduction enzymes, phase 2 conjugation enzymes, antioxidant support, and metallothionein upregulation. In general, phase 1 can generate dangerous reactive compounds, phase 2 conjugates those compounds to make them less toxic, and antioxidants help protect tissues between phases.

Detoxification pathways must be balanced to ensure more complete detoxification and elimination and antioxidant support during the phases that generate oxidative stress.

Research suggests that whole foods are preferred to high doses of individual food components, which may have unwanted effects on detoxification enzymes. Whole foods have a balance of compounds that helps modulate detoxification pathways without excessively activating or inhibiting pathways (Hodges 2015):

Whole foods

• Alfalfa sprouts
• Apiaceous vegetables (e.g., carrots, parsnips, celery, parsley, dill)
• Apples
• Apricots
• Artichokes
• Avocado
• Beets
• Berries (e.g., blueberries, black raspberries)
• Black currant
• Citrus
• Coconut
• Coffee
• Cruciferous vegetables (e.g., broccoli, cabbage, kale, Brussels sprouts)
• Curry powder
• Garlic
• Ginger
• *Grapefruit
• Grapes
• Green beans
• Greens (e.g., spinach, watercress, garden cress, parsley, dandelion greens, mustard greens, seaweed)
• Honey
• Legumes (e.g., peanuts, soybeans, lentils, peas, butter beans, adzuki beans, mung beans, chickpeas)
• Nuts (e.g., almonds, walnuts, Brazil nuts, pistachios, pignoli)
• Olives
• Onions, leeks
• Peppermint tea
• Pomegranate
• Protein (fish, seafood, eggs, poultry, lean meat, dairy products)
• Pumpkin seeds
• Quinoa
• Rosemary
• Seeds (e.g., sunflower, pumpkin, sesame)
• Spirulina
• Sweet potato
• Tea, black, green
• Tomatoes
• Turmeric
• Walnuts
• Watercress
• Whole grains (e.g., oats, barley, rye, amaranth, teff)

*Grapefruit juice may interfere with the breakdown of pharmaceuticals and cause a significant drug-nutrient interaction.

Source: Institute for Functional Medicine. Applying Functional Medicine in Clinical Practice.

Genetic factors influence detoxification

Variations in the genes that code for detoxification enzymes, especially the CYP and the GST enzymes, can affect how efficiently someone can break down and eliminate toxins (Raymond 2021).

Single nucleotide polymorphisms (SNPs) that affect phase 1 and 2 detoxification can be identified through advanced testing. However, it has yet to be confirmed that specific variants will have specific detoxification outcomes in humans, especially considering individual factors, including gender, smoking, and lifestyle habits.

Until more definitive guidelines are available, researchers recommend combining functional biomarkers of detoxification, including GGT, homocysteine, and oxidized LDL, with genetic testing and lifestyle assessment when evaluating detoxification competency (Aronica 2022).

Acid-alkaline balance influences detoxification

Consuming an alkalizing diet can support detoxification, especially the elimination of toxins through the kidney. The most alkalizing foods in general are fruits and vegetables, while the most acid-forming foods are meat, fish, grains, and cheese. Urine pH reflects dietary acid load and can change within two hours of dietary intervention. An alkalizing diet increases urine alkalinity and pH; an increase of 2 points on the urine pH scale can significantly increase the clearance of detoxified compounds. An acidic diet also usurps alkaline reserves throughout the body and compromises cell and tissue metabolism. For example, if the diet is too acidic, the body can counteract that acidity by releasing alkalizing calcium and magnesium from the bone. This process improves acid-base balance at the expense of bone integrity (Minich 2007).

Foods and nutrients that modulate the activity of Phase 1/Phase 2 enzymes and their interaction with genotype.

Source: Aronica, Lucia et al. “Genetic Biomarkers of Metabolic Detoxification for Personalized Lifestyle Medicine.” Nutrients vol. 14,4 768. 11 Feb. 2022, doi:10.3390/nu14040768 This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

A core food plan to support detoxification: (Cline 2015)

• Balanced macronutrient breakdown, e.g., 40% of calories from carbohydrates, 30% from protein, and 30% from healthy fats
• Five or more servings of fruits and vegetables
• ½ ounce of fluid for each pound of body weight (30 mL/kg)

Support Phase 1 detoxification

• • Avoid charbroiled meats, excess caffeine, excess alcohol
  • Minimize grapefruit, saturated, and hydrogenated fats
  • Increase cruciferous vegetables and ensure adequate high-quality protein intake

Support Phase 2 detoxification

• • Promote glucuronidation
    • Alpha- and beta-carotene-rich foods, e.g., pumpkin, carrots, squash, sweet potato, red peppers, collards, dandelion greens, cantaloupe, romaine lettuce
    • Quercetin-rich foods, e.g., apples, onions, kale, cherries, red wine, extra virgin olive oil, beans, broccoli, tea
    • Chrysin and luteolin-rich foods, e.g., broccoli, chili pepper, celery, rosemary, honey
    • Glucaric acid-rich foods, e.g., apples, alfalfa sprouts, broccoli, Brussels sprouts, adzuki beans, tomato, cauliflower, mung beans, cherries, apricots, spinach, oranges, tangerines
    • Watercress and turmeric
    • Dietary fiber from plant-based foods
    • Magnesium-rich foods, e.g., halibut, almonds, cashews, soybeans, spinach, oatmeal, potatoes, peanut, wheat bran, black-eyed peas, baked beans, brown rice, lentils, avocado, pinto beans
  • Promote sulfation
    • Sulfur-rich foods, e.g., scallop, lobster, crab, peanut, shrimp, mussel, chicken, Brazil nuts, haddock, sardine, cod, oyster, dried peach, eggs, turkey, almonds, cheddar cheese, Parmesan cheese, dried skim milk, spinach, onion, cabbage, Brussels sprouts, chickpeas, figs, beans/peas, leeks, endive, potatoes
  • Promote methylation
    • Folate-rich foods, e.g., liver, chicken giblets, egg yolks, dried beans, lentils, split peas, soybeans, almonds, whole wheat, potato, sweet potato, spinach, beetroot, Brussels sprouts, broccoli, cauliflower, kale, cabbage, bok choy, asparagus, bananas, oranges, peaches
    • Vitamin B12-rich foods, e.g., liver, chicken, fish, egg, milk, cheese, yogurt, clams, rainbow trout, salmon, haddock, tuna
  • Glutathione support
    • Cysteine-rich foods, including duck, yogurt, egg yolks, whey protein, ricotta cheese, cottage cheese, red peppers, garlic, onions, broccoli, Brussels sprouts, oats, granola, wheat germ, sprouted lentils.

Sample Nutrition Supplement Protocol to Support Detoxification (Noland 2020)

• Full-spectrum, high-quality multivitamin and mineral formula including bioavailable nutrient forms
• Buffered vitamin C (with mineral ascorbates): 1000– 4000 mg a day in divided doses (to avoid loose stools) in powder, capsule, or tablet forms during periods of increased detoxification. If dosage causes loose stools, lower the dose.
• Milk thistle (Silybum marianum) : 200– 600 mg silymarin/ day
• Rosemary (Rosmarinus officinalis) extract: 200– 500 mg dry extract/ day (standardized to 6– 10% rosmarinic acid)
• Turmeric curcuminoids with bioavailability enhancer (e.g., turmeric essential oils, cyclodextrin, piperine): 200– 600 mg curcuminoids/ day, in divided doses
• Astaxanthin (from Haematococcus pluvialis): 5– 20 mg/ day
• Vitamin B6 (as pyridoxal 5′-phosphate): 10– 25 mg/ day
• Vitamin B12 (as methylcobalamin): 500– 10,000 μg/ day
• Folate as (6S)-5-methyltetrahydrofolate (glucosamine salt), calcium methylfolate, or food-form folates: 1500 μg/ day
• Omega-3 fatty acids (as EPA and DHA): 2000– 5000 mg/ day
• Liposomal glutathione: 400– 800 mg/ day
• Additional supplements (for use under medical supervision):
  • N-acetylcysteine: 500– 1000 mg a day
  • Amino acids: taurine 500 mg twice/ day, glycine 500 mg twice/ day
  • Alpha-lipoic acid: 100– 600 mg a day
  • L-carnitine: 1000– 2000 mg a day in divided doses
  • Bioflavonoids (citrus, pine bark, grape seed, green tea): 50 mg/ day

References

Aronica, Lucia et al. “Genetic Biomarkers of Metabolic Detoxification for Personalized Lifestyle Medicine.” Nutrients vol. 14,4 768. 11 Feb. 2022, doi:10.3390/nu14040768 This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 

Cline, John C. “Nutritional aspects of detoxification in clinical practice.” Alternative therapies in health and medicine vol. 21,3 (2015): 54-62.

Hodges, Romilly E, and Deanna M Minich. “Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application.” Journal of nutrition and metabolism vol. 2015 (2015): 760689. doi:10.1155/2015/760689

Minich, Deanna M, and Jeffrey S Bland. “Acid-alkaline balance: role in chronic disease and detoxification.” Alternative therapies in health and medicine vol. 13,4 (2007): 62-5.

Noland, Diana, Jeanne A. Drisko, and Leigh Wagner, eds. Integrative and functional medical nutrition therapy: principles and practices. Springer Nature, 2020.

Raymond, Janice L., et al. Krause and Mahan's Food & the Nutrition Care Process. Elsevier, 2021.