[www.ncbi.nlm.nih.gov]

Various whole foods such as cruciferous vegetables [2, 4, 5], berries [6], soy [7], garlic [8, 9], and even spices like turmeric [10, 11] have been suggested to be beneficial and commonly prescribed as part of naturopathic-oriented and functional medicine-based therapies [12, 13].

The CYP1A family is involved in metabolizing procarcinogens, hormones, and pharmaceuticals. It is well-known for its role in the carcinogenic bioactivation of polycyclic aromatic hydrocarbons (PAHs), heterocyclic aromatic amines/amides, polychlorinated biphenyls (PCBs), and other environmental toxins [18, 19]. Low CYP1A2 activity, for example, has been linked to higher risk of testicular cancer [20].

CYP1 enzymes are also involved in the formation of clinically relevant estrogen metabolites: CYP1A1/1A2 and CYP1B1 catalyze the 2-hydroxylation and 4-hydroxylation of estrogens, respectively [22]. The potential role of 4-hydroxyestradiol in estrogen-related carcinogenesis, via the production of free radicals and related cellular damage [22], has prompted investigation into factors that modulate CYP1 enzymes.

Various foods and phytonutrients alter CYP1 activity (Tables ?(Tables1(a)1(a) and ?and1(b)).1(b)). Cruciferous vegetables have been shown, in humans, to act as inducers of CYP1A1 and 1A2, and animal studies also suggest an upregulation of CYP1B1 [4, 23–27]. The inductory effect of crucifers on CYP1A2 seems especially well established. Clinical studies also indicate that resveratrol and resveratrol-containing foods are CYP1A1 enhancers [28]. Conversely, berries and their constituent polyphenol, ellagic acid, may reduce CYP1A1 overactivity [6], and apiaceous vegetables and quercetin may attenuate excessive CYP1A2 action [24, 29]. Cruciferous vegetables and berries have been suggested as possible modulators of estrogen metabolites: berries for their reducing effect on CYP1A1 [6] and cruciferous vegetables for their stronger induction of CYP1A versus 1B1 enzymes [25–27, 30].

Curcumin at 0.1% of the diet has been shown, in animals, to induce CYP1A1, for example, [35], yet a diet of 1% turmeric was inhibitory [46]. Black tea at 54 mL/d induced both CYP1A1 and 1A2 [33], yet 20 mg/kg of theaflavins was inhibitory to CYP1A1 [45].

The large CYP2 family of enzymes is involved in the metabolism of drugs, xenobiotics, hormones, and other endogenous compounds such as ketones, glycerol, and fatty acids [15, 54]. Some notable polymorphisms occur in the CYP2C and CYP2D subgroups, leading to the classification of patients as “poor metabolizers” of various pharmaceuticals: warfarin and CYP2C9, antiarrhythmia agents, metoprolol and propafenone, and CYP2D6, phenytoin, cyclobarbital, omeprazole, and CYP2C19, for example, [15, 17]. CYP2D polymorphisms may be associated with Parkinson's disease and lung cancer [15]. Clinical evidence exists for the induction of CYP2A6 by quercetin and broccoli [4, 29] (Table 2(a)). In animals, chicory appears to induce CYP2A enzymes [41] and rosemary and garlic may upregulate CYP2B activity [9, 37]. Clinical studies using resveratrol and garden cress indicate CYP2D6 inhibition [28, 55] (Table 2(b)). Ellagic acid, green tea, black tea, and cruciferous vegetables also appear to inhibit various CYP2 enzymes.

[NOTE: COCONUT OIL HAS MCTs]

Watercress and garlic are CYP2E1 inhibitors in humans [59, 60]. In vivo evidence also suggests that N-acetyl cysteine, ellagic acid, green tea, black tea, dandelion, chrysin, and medium chain triglycerides (MCTs) may downregulate CYP2E1 [33, 43, 54, 61, 63, 64]. MCT oil may specifically attenuate the ethanol-induced upregulation of CYP2E1 and production of mitochondrial 4-hydroxynonenal, a marker of oxidative stress [64].

The occurrence of the different CYP3A isoforms is tissue-specific [15]. Rooibos tea, garlic, and fish oil appear to induce the activity of CYP3A, 3A1, and 3A2 [8, 36, 69, 70] (Table 3(a)). Possible inhibitory foods include green tea, black tea, and quercetin [33, 56, 71, 72] (Table 3(b)). The most clinically relevant of the enzymes is CYP3A4, which is expressed mainly in the liver and to a lesser extent in the kidney [13]. Caffeine, testosterone, progesterone, and androstenedione are substrates of the CYP3A4 enzyme system, as are various procarcinogens including PAHs and aflatoxin B1 [15]. To date, however, the principal driver for research on CYP3A4 has been due to its role in the metabolism of over 50 percent of all pharmaceuticals [73]. The potential for drug interaction with this single enzyme, coupled with the wide interindividual differences in enzymatic activity, generates some level of risk in administration of high doses and multiple drugs as well as food-drug and herb-drug interactions. Grapefruit juice is perhaps the most well-known food inhibitor of this enzyme [74], though resveratrol and garden cress, a member of the cruciferous vegetable family, appear to have similar effects in humans, albeit at intakes above what would be expected without high-dose supplementation [28, 55]. Curcumin may upregulate 3A4 activity [11].

The CYP4B1 isoform is involved in the metabolism of MCTs (medium chain triglycerides), as well as the bioactivation of pneumotoxic and carcinogenic compounds [78].

this subgroup may be associated with bladder cancer [15] and colitis [79]. A report by Ye et al. (2009) which examined the link between colitis and CYP4B1 activity found that the promotion of CYP4B1 activity by caffeic acid (found in caffeine-containing foods) (Table 4) correlated with reduced inflammation and disease activity [79]. Green tea may act to induce CYP4A1, as suggested by animal studies [40].

It is conceivable that modulation of phase II enzymes by food-based bioactive compounds may be advantageous in patients who have altered enzyme activity due to genetic polymorphisms or who have a high toxic burden due to chronic exposure to environmental pollutants, overactive phase I activity, or hormonal imbalance.

UDP-Glucuronosyltransferases

This class of enzymes, comprising multiple proteins and even subfamilies, plays an essential role in enhancing the elimination of biotransformed toxins in urine and feces, as well as metabolizing steroid hormones and bilirubin [84, 85].

Clinical and observational studies point to cruciferous vegetables, resveratrol, and citrus as foods and bioactive compounds that induce UGT enzymes [25, 28, 90–92]

In vivo research suggests that polyphenol extracts of certain berries, specifically strawberries and blackcurrant, may inhibit beta-glucuronidase activity in the intestinal lumen; Kosmala et al. (2014) observed this effect using both strawberry pomace water extract and water-alcohol extract containing 5.1% and 17.1% ellagic acid, and 0.2% and 10.9% proanthocyanidins, respectively [100].

Inhibition of UGT enzymatic activity may be a consideration for modulation of hormone levels and the risk of certain cancers, such as prostate cancer [84]. In vitro studies suggest that various foods and food-based components may inhibit UGT activity, including green and black tea, quercetin, rutin, naringenin, allspice, peppermint oil, cacao, and silymarin [84]

caffeine and retinoic acid are possible SULT inducers according to animal studies [107, 108] (Table 6(a)). Although it is uncertain how their outcomes will translate in vivo, various in vitro studies have indicated the possibility of sulfotransferase inhibition (including competitive inhibition) by wine anthocyanins and flavonols, synthetic food colors (especially red colors), apple and grape juice, catechins including epigallocatechin gallate, quercetin, curcumin, resveratrol, flavonoids (apigenin, chrysin, fisetin, galangin, kaempferol, quercetin, myricetin, naringenin, and naringin), and certain phytoestrogens (daidzein, genistein) [3, 105].

Cruciferous and allium vegetables and resveratrol demonstrate ability to induce GSTs in humans [28, 114–117]

Support for glutathione conjugation also involves enhancing reduced glutathione (GSH) status. Glutathione is a low-molecular weight tripeptide containing residues of cysteine, glutamate, and glycine [136].

N-acetyl cysteine has also been used to restore depleted GSH levels in a clinical setting [139].

Various nutrients may also enhance endogenous glutathione synthesis, including vitamin B6, magnesium, and selenium [140, 141]. Curcuminoids (from turmeric), silymarin (from milk thistle), folic acid, and alpha-lipoic acid have been shown, in humans, to restore depleted GSH [129, 130, 142, 143]. In animal studies, cruciferous vegetables and artichoke have also demonstrated a GSH-protective effect [131–133].

Amino acids of various types (e.g., taurine, glycine), whether endogenous or exogenous (from dietary sources) in origin, can be utilized for attaching to molecules for their excretion. For the benefit of providing a substrate to these enzymes, it is generally thought that dietary protein is required for an effective detoxification protocol.

Research demonstrates that dietary components, especially phytochemicals, not only scavenge reactive oxygen species, thereby acting as direct antioxidants, but also regulate Nrf2 activity [150]. In vivo evidence exists for Nrf2-modulation by curcumin [155–158], broccoli constituents [159, 160], garlic [161–163], epicatechins [164–167], resveratrol [168, 169], ginger [170, 171], purple sweet potato [118], isoflavones [172, 173], coffee [174], rosemary [175, 176], blueberry [166, 177], pomegranate [178], naringenin [179], ellagic acid [166], astaxanthin [166], and ?-tocopherol [180]

Various studies point to the advantageous effects of whole foods, and food combinations, versus specific bioactive compounds. Zhou et al. (2014)

overexpression of Nrf2 is found in many cancer cells and has been shown to promote tumor growth and resistance to anticancer therapy [154]. Consequently, the inhibition of Nrf2 signaling may be clinically relevant for patients receiving cancer chemotherapy [184, 185]. Overexpression of Nrf2 and CYP2E1 has also been associated with impaired GLUT4 activity and insulin resistance [68].

Metallothionein, a cysteine-rich protein with the ability to bind divalent cations, including toxic metals such as mercury, cadmium, lead, and arsenic, is gaining recognition as an important component in heavy metal detoxification [190–192].

In addition to sequestering heavy metals, it is capable of scavenging free radicals and reducing injury from oxidative stress [192], as well as inhibiting NF-?B signaling [193].

Dietary patterns and nutrients may result in changes in metallothionein production. Lamb et al. (2011) reported a 54% increase in metallothionein mRNA production in a small clinical trial in women with fibromyalgia following an elimination diet in conjunction with a phytonutrient-rich medical food consisting of hops, pomegranate, prune skin, and watercress [194]. Zinc supplementation (15 mg/day) to healthy men over 10 days led to significantly increased metallothionein mRNA, up to 2-fold in leukocytes and up to 4-fold from dried blood spots [195].

Based on the four systems examined in this paper, there are several foods which seem to have demonstrated an influence on detoxification systems.

This recent scientific update notes clinical evidence of effects from cruciferous vegetables (in combination, and specifically watercress, garden cress, and broccoli), allium vegetables, apiaceous vegetables, grapefruit, resveratrol, fish oil, quercetin, daidzein, and lycopene.

studies have revealed that exposure to and accumulation of toxins play a significant role in cardiovascular disease, type 2 diabetes, and obesity [203–207]. Thus, one's dietary intake and environmental influences may have large bearing on the incidence of chronic disease.

Garlic and turmeric are not food according to Dough Graham.
You cannot make a meal with any of them.
When was the last time children were licking their fingers eating garlic?

Garlic and turmeric may not be foods, but they are useful for some people some of the time. Children may not lick their fingers after eating garlic, but I do. Yes, I know, I know, it is supposedly a poison which will ruin my brain. My interpretation of this is: it is a powerful dewormer, and when worms die off this can make you crazy. The rest of us use it moderately, as needed.

1 Dough Graham eats sesame seeds.

2 But he does not make a meal out of sesame seeds.

3 When was the last time children were licking their fingers eating sesame seeds?

Quote
Panchito
1 Dough Graham eats sesame seeds.

2 But he does not make a meal out of sesame seeds.

3 When was the last time children were licking their fingers eating sesame seeds?

LOL!

While I'm here, brown (unrefined, natural) sesame seeds are particularly high in anti-nutrients.

Traditional peoples knew what they were doing when they refined their foods, at least sometimes. E.g., Japanese refining their rice to a greater or lesser degree (brown rice is notoriously high in anti nutrients); Africans using elaborate cooking methods to cook certain grains, etc. before eating it. Here in the west, the Weston Price bunch recommend certain soaking practices for grains. (If you wish to eat some cooked food). Also for seeds and nuts.

However, Weston Price followers are plum crazy about animal foods, because they are high in nutrients. As if that is the only issue. Meh.



Edited 1 time(s). Last edit at 01/05/2023 12:04AM by Horsea.