Life Extension Magazine®

Issue: Nov 2012

EPIGENETICS for Breast Cancer Prevention

Up to 50% of breast cancer cases are thought to be preventable through simple changes in diet and lifestyle. The science of epigenetics uses nutrients and certain drugs to regulate genes, thereby changing the way breast cancer cells age and reproduce.

By Alexander Johnson.

EPIGENETICS for Breast Cancer Prevention

Every year, nearly 250,000 women learn that they have invasive breast cancer. Roughly 58,000 more will be diagnosed with early cases of the disease.1 And about 40,000 will die.2

Some women are so paralyzed by the fear of this disease that they undergo double mastectomies in a drastic attempt to prevent it from occurring.

Despite these dire numbers and drastic actions, there is hope for the prevention of breast cancer. And it doesn't come in the form of risky surgical procedures—it comes from nature itself.

Up to 50% of breast cancer cases are now thought to be preventable through simple changes in diet and lifestyle.3,4 The use of specific agents to prevent cancer from developing is called chemoprevention. Utilized properly, chemoprevention should be able to eliminate pre-malignant cells, block the progression of normal cells into invasive tumors, and ultimately stop a cancer before it ever reaches a size that could cause symptoms or be detected.5

Research has demonstrated that there are scores of nutrient molecules with potent, and often multiple chemotherapeutic effects. For example, calcium, selenium, and vitamin D have all shown some effect in reducing cancer occurrence.6 An even larger array of nutrients is responsible for changes that promise powerful chemoprevention against breast cancer.7

In this article we'll explore some of the most exciting implications of the power of nutritional supplementation to prevent breast cancer. Then we'll give you a rundown of nearly three dozen specific nutrients that hold out special hope in the fight against this epidemic killer.

Revolutionary New Science Holds The Key to Breast Cancer Prevention

A relatively new science called epigenetics has shed light on the enormous control we as individuals have on whether or not we develop cancer. The science of epigenetics is the study of long-lasting changes in gene function that do not involve changes in gene structure.9 Epigenetics has taught us that we can use factors such as nutrients to turn a gene on and off.10

If the gene that's activated is a tumor-suppressor gene (a gene that prevents excessive cell replication), or one that triggers termination of defective cells (such as pre-malignant cells through normal apoptotic processes), these epigenetic modifications are capable of blocking the progression of a cancer cell.10

The science of epigenetics has finally explained how nutrients and certain drugs can change the way breast cancer cells age and reproduce.9

Based on the science of epigenetics, Big Pharma is now racing to produce chemopreventive drugs.7 But nature is far ahead, as usual. Scores of researched nutrients have potent, and often multiple, epigenetic and chemotherapeutic effects (Table 1)—without the side effects associated with drugs like tamoxifen, which the FDA approved for breast cancer prevention.

In the next section, we'll look at nature's most powerful chemopreventive nutrients (and a few drugs), how they work, and what they may mean for the future of breast cancer.11

TABLE 1. Risk Reduction for Breast Cancer By Specific Compounds
TABLE 1. Risk Reduction for Breast Cancer By Specific Compounds
Nutrient Reduction in Breast Cancer Risk
Aspirin 20-32%62,66,146
Coffee 40%147
Conjugated Linoleic Acid 60%148
Fish Oil, Omega-3 Fats 73-81%149
Green Tea 22-48%150-152
Lycopene 40-68%153-155
Melatonin 38%156
Metformin 23-56%157,158
Resveratrol 61%159
Soy & Soy Isoflavones 18-92%160-162
Vitamin D 11-44%87,163

Nature's Cancer-Preventing Nutrients

What follows are 11 categories of targeted nutrients that have been studied for their impact on breast health and cancer prevention. You can choose what combination of nutrients would be most effective for your situation. At the end of this report is a dosing table.

Most of the nutrients in this list have multiple ways in which they help to prevent cancer. That's because each individual nutrient has many different biochemical targets in breast cancer prevention. Because cancer has multiple causes and phases of development, scientists are well aware that a multi-targeted approach is the best way to attack a disease like cancer.

1. Nutrients that Prevent DNA Damage

Breast cancer, like all others, invariably begins with some change to the DNA structure or function of an individual cell. Both DNA damage and a change in the way a normal gene is expressed can trigger a cell to become malignant. In either case, a tumor suppressor gene can become silenced, allowing unregulated cell replication, or a tumor promoter gene can become activated. However, many nutrients work to prevent the DNA damage that can lead to a cell becoming cancerous.

The list of nutrients proven to have anti-breast cancer effects is long, a tribute to the role of oxidant damage in breast cancer formation. Antioxidant nutrients proven to have anti-breast cancer effects include:

  • Coenzyme Q10 (CoQ10)14-17
  • Coffee and many of its constituents18-20
  • Curcumin21-23
  • Green tea polyphenols, especially epigallocatechin gallate (EGCG)24
  • Indole-3-Carbinol (I3C)25
  • Lycopene26,27
  • Melatonin28
  • Metformin29
  • N-acetylcysteine (NAC)30-35
  • Pomegranate juice and extracts36-38
  • Resveratrol39
  • Selenium40
  • Silibinin and silymarin21,41-47
  • Soybean flavonoids genistein and diadzein 40,47
  • Sulforaphane48
  • Tocotrienols49-53

2. Nutrients that Control Regulatory Genes

Processes called hypermethylation and histone deacetylation can unlock undesirable epigenetic expression or suppress regulatory genes. Fortunately, a number of nutrients block these processes, and therefore can help to prevent the epigenetic changes that lead to breast cancer. These include:7,11

  • Omega-3 fatty acids from fish oil54
  • Lycopene55
  • Genistein, a soy isoflavone55
  • Resveratrol56,57
  • Caffeic acid, a component of coffee19
  • Sulforaphane from cruciferous vegetables10,58,59
How Starch and Fiber Differ— And Why it Matters to You
Activate Powerful Cancer Protection with Natural Nutrients
  • Breast cancer threatens the lives of millions of women.
  • Breast cancer is caused by a complex interaction of multiple dietary, lifestyle, environmental, and genetic factors.
  • The science of epigenetics, the study of how genes can be expressed differently without changes in actual gene structure, has provided profound new insights into breast and other cancers.
  • A large number of nutrients have now been found to exert favorable epigenetic effects on breast cancers from the moment a cell undergoes malignant transformation through the fully-developed tumor's attempts to invade and metastasize.
  • Nutrient-based epigenetic chemoprevention represents an entirely new front in the battle against breast cancer.

3. Nutrients that Fight Cancer-Promoting Inflammation

Once a cell has become malignant, inflammation is a powerful epigenetic promoter of the next steps in the process of cancerous transformation.60 Nature provides many natural anti-inflammatory molecules with specific promise in breast cancer chemoprevention, including the following:

  • Acetylsalicylic acid (aspirin)61-66
  • Conjugated linoleic acid (CLA)67,68
  • Coffee compounds18,69
  • Curcumin70,71
  • Omega-3 fatty acids EPA and DHA from fish oil72
  • Pomegranate extracts73
  • Quercetin74
  • Resveratrol39
  • Vitamin D75

4. Nutrients that Block Excessive Cell Replication

The excessive rate of cell replication is one of cancer's best-known features. Many nutrients are capable of blocking the continuous churning of the cellular replication cycle and slowing or stopping cancer growth, which ultimately contributes to breast cancer chemoprevention through epigenetic means. These include:

  • Apigenin, a yellow flavone molecule found in many plants76
  • Aspirin77
  • Coffee components78
  • Indole-3-Carbinol (I3C) from cruciferous vegetables79,80
  • Melatonin81
  • Pterostilbene, a close relative of resveratrol82
  • Selenium83
  • Sulforaphane from cruciferous vegetables10,84

5. Nutrients that Transform Malignant Cells Back into Healthy Ones

Breast carcinoma
Breast carcinoma

Even after cells have undergone malignant transformation, there's a chance to reverse that process by forcing them to "differentiate" back into normal tissue-forming cells. Nutrients that promote the differentiation of breast cancer cells include:

  • Conjugated linoleic acid (CLA)85
  • N-acetylcysteine (NAC)32
  • Vitamin D86,87
 
Breast Cancer Facts
  • Breast cancer is the most common cancer among women in Western countries.12-13
  • It takes a greater toll on women 40 or older, among whom 95% of new cases and 97% of deaths occur.
  • The median age at breast cancer diagnosis is 61 years.
  • The peak incidence of the disease occurs between ages 75 and 79, with 421 new cases per 100,000 women.1

6. Nutrients that Trigger the Death of Cancer Cells

A powerful natural means of controlling cell replication is the process of apoptosis, or programmed cell death. Normal cells have the ability to self-destruct if they receive signals that they are replicating too rapidly. Malignant cells lose this ability, contributing to their overwhelming growth rate. A number of nutrients have the ability to restore breast cancer cells' ability to die by apoptosis, including the following:

  • Apigenin76,88,89
  • Coffee compounds78
  • Conjugated linoleic acid (CLA)90
  • Curcumin91,92
  • Green tea polyphenols and EGCG24
  • Indole-3-Carbinol (I3C)79,93
  • Melatonin94
  • N-acetylcysteine (NAC)95
  • Pomegranate96,97
  • Quercetin98
  • Selenium83
  • Silibinin99
  • Soy Isoflavones97,100,101
  • Tocotrienols102,103
  • Vitamin D94

7. Nutrients that Restore Receptors that Enhance Standard Treatments

7. Nutrients that Restore Receptors that Enhance Standard Treatments

Roughly 70% of breast cancer cells depend on a continuous supply of estrogen for their growth, while a smaller number of cancers depend on the growth factor called HER2/neu. These cancers can potentially be treated by interfering with the receptors, making them (at least in theory) less dangerous.

Between 15 and 25% of breast cancers, however, are so-called "triple-negative" cancers, meaning that they lack any of the three receptors (estrogen, progesterone, or HER2/neu), and are correspondingly resistant to treatment. Among the most exciting discoveries in the epigenetics of nutrients for cancer chemoprevention is that many nutrients can restore one or more of those receptors to the surface of breast cancer cells, lowering the bar to effective standard treatments such as the estrogen receptor blocker tamoxifen.15

Other nutrients can modify at least one of the receptors, impairing the cells' ability to receive the growth signals they require, and triggering their early death.

Nutrients (and a drug) capable of epigenetic chemoprevention through modification or restoration of breast cancer receptors, or which have effectiveness against triple negative cancers include:

  • Coffee104,105
  • Conjugated linoleic acid (CLA)106
  • Curcumin107
  • Green tea polyphenols11,108
  • Melatonin109
  • Metformin110
  • Omega-3 fatty acids from fish oil111
  • Sulforaphane from cruciferous vegetables11,112

8. Nutrients that Inhibit Estrogen Production

The enzyme aromatase is responsible for producing estrogen in body tissues, including breast cells. Therefore, inhibiting aromatase activity is an important means of slowing the growth of the 70% of estrogen-dependent breast cancers. Nutrients capable of chemoprevention through aromatase inhibition include:

  • Chrysin113
  • Enterolactone from lignan extract114
  • Grape seed extract115
  • Hops extracts116
  • Melatonin109
  • Pomegranate117
  • Vitamin D75

Note: aromatase inhibiting drugs like Arimidex® (anastrozole) have far more potent estrogen-suppressing effects, but they lower estrogen so much that they can induce severe menopausal effects.

9. Nutrients that Block Abnormal Growth Factors

In addition to estrogen, progesterone, and HER2/neu, a number of other growth factors act on breast cancer cells. Inhibition or epigenetic modification of these growth factors is a major target in breast cancer chemoprevention, especially by the following nutrients:

  • Apigenin118
  • Conjugated linoleic acid (CLA)119
  • Curcumin92
  • Gamma tocotrienol120
  • Green tea polyphenols108,121
  • Indole-3-Carbinol (I3C)80
  • Melatonin94
  • Omega-3 fatty acids111
  • Silibinin41
  • Sulforaphane59
  • Vitamin D94
Breast Cancer: The Basics
Breast Cancer: The Basics
Growing tumor

By the time breast cancer is detectable, it has already gone through a lengthy and complex series of events that turned a normal, healthy cell into a cancerous one. Basically, cancer occurs when cellular replication has gone awry.8

In a healthy body, excess cell replication is under tight control by genetic signals from genes called tumor suppressor and suicide genes.5 When a tumor suppressor gene is turned on in response to an abnormal signal, it prevents cell division from getting out of control. Similarly, the activation of a suicide gene triggers a programmed form of cell death called apoptosis.

Ultimately, the development of cancer is the direct result of how genes express themselves in tissues. Cancers form when the function of a gene changes—either activating cancer-producing genes, or deactivating cancer-suppressing genes.7

10. Nutrients that Cut Off the Blood Supply to Growing Tumors

Once a cancer has begun its rapid growth phase, it requires a vast increase in its blood supply. Tumor cells are capable of inducing new blood vessel growth (angiogenesis) through multiple epigenetic mechanisms. A number of nutrients are capable of reversing that process and depriving growing tumors of blood supply. These include:

  • Apigenin122-124
  • Coenzyme Q10 (CoQ10)17,125
  • Coffee diterpenes18
  • Conjugated linoleic acid (CLA)85
  • Curcumin126
  • Grape seed extract127,128
  • Green tea129,130
  • Indole-3-Carbinol (I3C)79
  • Lycopene27
  • Melatonin27
  • N-acetylcysteine (NAC)30,33,34
  • Omega-3 fatty acids131
  • Pomegranate132
  • Quercetin74
  • Silibinin133
  • Soy isoflavones134-136
  • Vitamin D75,86

11. Nutrients that Prevent Tumors from Spreading

11. Nutrients that Prevent Tumors from Spreading
Growing tumor

Growing tumors develop the ability to invade local and regional tissues, and to "seed" other body areas with malignant cells through the process of metastasis. To accomplish these processes, tumors increase their production of "protein-melting" enzymes called matrix metalloproteinases, or MMPs. Effective chemoprevention involves epigenetic changes that impair tumors' production of MMPs, as is seen in the activities of these nutrients (and drugs):

  • Coenzyme Q10 (CoQ10)137
  • Coffee diterpenes and phenolics18,138
  • Conjugated linoleic acid (CLA)139
  • Cruciferous vegetable components sulforaphane and isothiocyanates140
  • Curcumin141
  • Green tea polyphenols24, 121,130
  • Melatonin142
  • N-acetylcysteine (NAC)31
  • Silibinin41,42,133
  • Soy isoflavones101,135
  • Compounds that function via other mechanism to inhibit metastasis include:
  • Modified citrus pectin143+
  • Aspirin144
  • Cimetidine145+

+Note that cimetidine and modified citrus pectin are only used by those with existing cancers. They have not shown preventive effects.

Summary

Breast cancer, the leading malignancy among women, has long evaded attempts at prevention. However, breakthroughs in the science of epigenetics has led both to a greater understanding of how breast cancer forms—and ultimately to the discovery of novel approaches to chemoprevention.

A large number of nutrients are capable of beneficial epigenetic modifications in breast cancer cells. These nutrients are capable of impeding breast cancer initiation, promotion, proliferation, invasion, and metastasis. They accomplish these multiple effects through the activation of genes that suppress cancer, the deactivation of genes that promote cancer, the promotion of cancer cell death through apoptosis, the modification of hormonal and other growth factor receptors, and fundamental effects such as antioxidant and anti-inflammatory actions.

With the broad range of breast cancer chemoprevention available through nutrient supplementation, it only makes sense to include a wide variety of these supplements in your health promotion regimen.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

Breast Cancer Chemopreventive Nutrients 1 Breast Cancer Chemopreventive Nutrients 2

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Greg's CR Way™ Benchmarks Panel

Motivating observations from Greg: "The positive effects of the less easily quantifiable results interests me most, e.g., mood status, libido, energy, stress management, for example. In addition, I keep waking up earlier than usual. In my "pre-CR" life this would be due to stress. Now it results from increased energy. I am sure my memory has improved as I seem able to recall and quote scientific papers, telephone numbers, names, and the like. At 46, I expected my eyesight to slowly deteriorate but it has actually IMPROVED! All these benefits cannot be coincidences."

Greg is a highly motivated, accomplished individual in his personal life. Seeing him carry that into his CR practice—achieving a great deal in a short time—is wonderful. We imagine that he will enjoy even more benefits in the years to come, amazing his friends and family with his youthful life as the years roll by.

These successes can forecast yours. The CR Way™ is about practicing calorie restriction "as you like it." It encourages molding proven CR science to individual needs.

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.

Notes:

* Body Mass Index (BMI) is a measure that relates one's weight to height: The normal range starts at 18.5; overweight at 25; and obesity at 30.

To learn more about the CR Way™ or the CR Society International, visit www.LivingTheCRWay.com or www.CRSociety.org.


References

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2. McGlothin P, Averill M. The CR Way™: Using the Secrets of Calorie Restriction for a Longer, Healthier Life. New York, NY: HarperCollins; 2008:45-53.

3. Soare A, Cangemi R, Omodei D, Holloszy JO, Fontana L. Long-term calorie restriction, but not endurance exercise, lowers core body temperature in humans. Aging (Albany NY). 2011 Apr;3(4):374-9.

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5. Duffy PH, Feuers RJ, Hart RW. Effect of chronic caloric restriction on the circadian regulation of physiological and behavioral variables in old male B6C3F1 mice. Chronobiol Int. 1990(4);7:291-303.

6. Lane MA, Baer DJ, Rumpler WV, et al. Calorie restriction lowers body temperature in rhesus monkeys, consistent with postulated antiaging mechanisms in rodents. Proc Natl Acad Sci U S A. 1996 Apr; 93(9):4159–64.

7. Willcox BJ, Willcox DC, Todoriki H, et al. Caloric restriction, the traditional Okinawan diet, and healthy aging. Ann N Y Acad Sci. 2007 Oct;1114:434-55.

8. Enea C, Boisseau N, Fargeas-Gluck MA, Diaz V, Dugué B. Circulating androgens in women: exercise-induced changes. Sports Medicine. 2011 Jan 1;41(1):1-15.

9. Archer T, Fredriksson A, Johansson B. Exercise alleviates Parkinsonism: clinical and laboratory evidence. Acta Neurologica Scandinavica. 2011 Feb;123(2):73-84.

10. Powell KE, Paluch AE, Blair SN. Physical activity for health: What kind? How much? How intense? On top of what? Annu Rev Public Health. 2011 Apr 21;32:349-65.

11. O'Keefe JH, Vogel R, Lavie CJ, Cordain L. Exercise like a hunter-gatherer: a prescription for organic physical fitness. Prog Cardiovasc Dis. 2011 May-Jun;53(6):471-9.

12. Johnson RJ, Murray R. Fructose, exercise, and health. Curr Sports Med Rep. 2010 Jul-Aug;9(4):253-8.

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