Key Terms Calorie Restriction (CR) A dietary regimen that reduces the caloric intake of an individual without resulting in malnutrition or a reduction in the intake of essential nutrients. NAD+/NADH Ratio A high NAD+/NADH ratio increases the stimulation of a variety of genes in the mitochondria and is associated with high energy production. CR and benaGene™ both increase the NAD+/ NADH ratio. What is Calorie Restriction? Increasing longevity (or life span) is often considered nothing more than the goal of fictional mad scientists and sorcerers. However, caloric restriction (CR) has been extensively studied over the last 70 years, with numerous
Breast cancer is the most common
Xenoestrogens are a group of environmental chemicals
Phytoestrogens and breast cancer
It is impossible to talk about breast cancer and estrogen without briefly discussing phytoestrogens. There is a fair amount of confusion about the safety and effectiveness of phytoestrogens, even among medical professionals. Phytoestrogens are a group of compounds found
A large number of population studies that assess soy consumption found that higher intakes do not increase breast cancer risk. Some studies even showed a protective effect.15 After considering all the studies, a daily intake of 10g of soy protein had the optimal protective effect.15 These results are opposed by a number of test tube studies that have shown phytoestrogens in soy to stimulate estrogen receptors and breast cancer cell growth. The difference in the results highlights the complexity in phytoestrogen activity. One important point to consider is that individual differences in intestinal microflora in humans promote the formation of various phytoestrogen metabolites such as equol, which has a noted cancer protective effect.16 New data suggests that equol could possibly enhance the effect of tamoxifen in the prevention of breast cancer.17 These factors are not considered in test tube studies and may be responsible for the negative results.
While there still is more research to be done, population studies suggest that moderate dietary consumption does not increase the risk of breast cancer. It may even be protective, especially if the person has consumed soy since childhood. It’s also important to remember that not all phytoestrogens are the same and some may offer a greater protective effect than others.
The Influence of Diet on Estrogen and Breast Cancer Risk Reduction
Sulforaphane is a compound with a unique ability to stimulate the phase 2 liver detoxification system.20 The phase 2 pathway is very important since it is the final stage for the removal of harmful compounds, detoxification products, and excess estrogens. Sulforaphane also has an impressive range of anti-cancer activity beyond stimulating phase 2 detoxification including stimulation of cancer cell suicide, preventing replication, reducing tumor spreading and inhibiting blood supply to cancer cells.21 Numerous studies have shown that sulforaphane can prevent the growth of various cancer cells of the prostate, colon and breast.21 Perhaps the most exciting recently discovered action is that it may actually inhibit breast cancer stem cells which are responsible for continued tumor growth and disease relapse.22Another promising anti-cancer effect is the ability of sulforaphane to reduce inflammation right at the genetic level by stimulating a control protein called nuclear factor 2 (Nrf2).19
From a practical perspective, cruciferous vegetables contain high amounts of glucoraphanin (also referred to as sulforaphane glucosinolate or SGS), which is then converted to biologically active sulforaphane by an enzyme called myrosinase. Myrosinase is released when the plant is chewed or processed or produced in the gut by bacteria.19 See Figure 2 for a diagram of sulforaphane breakdown. Unfortunately, cooking partially destroys this enzyme, limiting sulforaphane production. Glucoraphanin is abundant in broccoli, cauliflower, cabbage, and kale, with the highest concentration found in broccoli and broccoli sprouts.19 Studies show that just 1 cup of raw broccoli sprouts contains enough sulforaphane (200 µmol) to penetrate breast tissue and stop cancer growth.23
I3C is another compound found in the cruciferous vegetable family, which has an impact on estrogen levels and breast cancer risk. Like sulforaphane, I3C possesses multiple anti-cancer mechanisms including the up- regulation of detoxification enzymes and increasing the 2-OHE1 form of estrogen in the liver.5 In controlled clinical trials, oral supplementation with 300–400 mg/ day of I3C has consistently increased urinary 2-OHE1 levels and urinary 2-OHE1:16α-OHE1 ratios in women.24,25 I3C supplementation also reversed a form of early cervical cancer after just 12 weeks of supplementation.26
Once I3C is ingested it
Supplementation with 108 mg/day of DIM also increased urinary 2-OHE1 levels in postmenopausal women suggesting that is has a positive effect on estrogen balance.27 One advantage DIM has over I3C is that it is a more stable molecule which leads to enhanced biological activity.28
Essential Fatty Acids
The omega-3 and omega-6 class of polyunsaturated fatty acids exert a modulating action on estrogen metabolism. High intake of omega-6 fatty acids – linoleic acid (LA) and arachidonic acid (AA) – interferes with the detoxification of estrogens. Omega-3 fatty acids refer to a group of three fats: alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Hydroxylation is an important biochemical process necessary for detoxification. EPA has been shown to increase 2-hydroxylation of E2 at the expense of C-16α hydroxylation, while DHA decreases the binding of estrogens to the ERs.
Dietary fibers are parts of a plant that do not break down in our
Recent studies demonstrate that 16α-OHE1 levels
The important role of vitamins B6, B12, and folate as cofactors for enzymes involved in the methylation of catechol estrogens (2-OHE1 and 4-OHE1) to less harmful metabolites has already been mentioned. However, obtaining B vitamins solely from the diet can represent quite a challenge, especially for the increasing number of individuals adhering to a gluten-free diet. A significant portion of the population presents single nucleotide
Green tea has a large range of potential anti-cancer actions including reducing the growth of cancer cells and the blood vessels that feed them. For a more detailed discussion on green tea and cancer please see the article in Advances: Cancer. A recent study added another benefit to the long list when it found that green tea actually blocked breast cancer growth associated with a powerful xenoestrogen called PhIP (found in grilled or fried meats).29 This is so important because xenoestrogens may be responsible for up to 85% of spontaneous breast cancers.29
Glucaric acid is found in many fruits and vegetables, with the highest concentrations in oranges, apples, grapefruit, and cruciferous vegetables. Oral supplementation of calcium- D-glucarate (a salt form of glucaric acid) has been shown to inhibit, an enzyme produced by gut bacteria that prevents phase II liver detoxification.30 Elevated beta- glucuronidase activity is associated with an increased risk for various cancers, particularly hormone-dependent cancers such as breast, prostate, and colon cancers.30 Calcium-D-glucarate’s inhibition of beta-glucuronidase activity allows the body to excrete hormones such as estrogen before they can become reabsorbed. support of this action, supplementation with calcium-D-glucarate has been shown to lower serum estrogen levels in rats by 23 percent.31
Pulling it all together
There is little doubt that estrogen plays a large role in breast cancer development and growth. Certain forms of
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