The impact of a variety of integrative medicines on breast cancer prevention, ancillary treatment, and the treatment of side effects has arguably more research accumulated compared to any other cancer. The field moves quickly and the ability to learn about the latest options that work and are worthless need to be reviewed whether they impact the consult with a patient directly or indirectly. Numerous integrative medicine terms or vernacular, along with lifestyle, diet, dietary supplement, environmental and other alternative medicine need a quick review and these can be found in this chapter and other sources [1–4].

Note: Many myths and misconceptions and integrative vernacular are already covered in the other chapters (especially Chap. 2), but included here are others that could not be addressed elsewhere in the book or simply needed more attention. There was also no need to include a table summary in this chapter versus the others because most subjects are brief overviews similar to a table format.

Acid reflux drugs (not just proton pump inhibitors or PPI but also histamine 2 receptor antagonist or H2 blockers) could increase the risk or been associated with B12 and/or magnesium deficiency (via absorption issues) [5, 6]. And reductions in iron and calcium absorption (higher risk of bone loss and fractures) have also been reported. Chronic use of these medications in cancer patients should be generally discouraged unless there is a clear indication of need.

This is an often utilized term to describe the impact of an herbal supplement that provides a multitude of homeostatic or overall balancing effects to the body, which is apparently not due to a specific compound in the dietary supplement but all the products working synergistically together to improve the health of the body. I have found this term to be utilized in some clinical discussions with integrative medicine practitioners that cannot generally refer to positive consistent clinical research but instead redirect the discussion to inform their specific audience that the product has “adaptogenic” potential. In reality, most of the herbal products I have researched are eventually found to have a standardized ingredient with efficacy if it works (or not)—just like a drug. For example, American and Panax ginseng were often referred to as adaptogens (almost the paradigm of the word adaptogen), but with increasing research it appears that “ ginsensosides ” are the active ingredients especially in the area of reducing cancer-related fatigue (CRF) [7, 8]. For example, two phase-3-like clinical trials have found a potential benefit of ginsenoside contents of 3–5 %. Salicin appeared to be the active (standardized to 120 mg or 240 mg salicin) low-back pain relieving ingredient in willow bark extract [9], “gingerols ” and other compounds in ginger for nausea [10], ….

No integrative medicine appears to replace a vaccination despite some in the integrative world believing that they are “unnatural.” However, it appears health care professionals could also do a better service by explaining the side benefits of some vaccines. For example, the reason that nothing replaces the flu shot is because it is designed based on the most current strains of virus that are infecting individuals around the world. It evolves and is up-to-date and no dietary supplement for the flu can do this. Second, the flu shot provides ancillary or side benefits just beginning to be appreciated, for example it appears to be reducing the risk of cardiovascular events such as heart attack and strokes [11]. And since cardiovascular disease is still the number 1 cause of death in women and men then any vaccine with that form of side benefit should receive more positive attention.

Flu and many other vaccinations do not just prevent disease but prevent the severity of disease even when infected [1]. And when receiving a vaccination such as the flu, one is conducting a selfless act via protecting more vulnerable elderly and children from being infected by life-threatening transmissible diseases. This is the concept called “Herd Immunity ,” which allows those that get vaccinated lower and lower disease prevalence and this also occurs for those individuals that are not vaccinated or those that were vaccinated but still highly susceptible to being infected (immune suppressed) [12, 13].

Multiple vaccines, via the pathway of preventing extreme systemic inflammatory reactions, appear to be cardioprotective. Interestingly, research on the shingles suggests it could increase the risk of a stroke, transient ischemic attack (TIA) and myocardial infarction even in younger individuals [14]. Thus, the shingles vaccine could potentially provide for cardiovascular protection. Hospitalization for pneumonia also appears to increase the risk of a cardiovascular short- and long-term cardiovascular disease (CVD) [15], and now two pneumonia vaccines are available to adults that qualify for them. Vaccines may also provide better immune regulation and surveillance and augment other treatment such as the recent tetanus toxoid injection that appeared to provide an enhanced neo-adjuvant preliminary treatment benefit in glioblastoma patients receiving immunotherapy treatment [16]. And the tetanus vaccination could be providing some protection against the risk of some autoimmune diseases (such as multiple sclerosis) [17, 18].

What region of the world has the world’s longest life expectancy right now [1, 19]?

Answer: Andorra (a trick question)?!

Andorra, more officially known as “The Principality of Andorra ,” occupies a small area on the border between France and Spain. It is a popular destination for skiing and shopping (over 2000 shops and tax-free), but it is more. It is roughly the size of New Orleans, LA, and was established in 1278, but became a democracy in 1993 (jointly ruled by France and Spain prior to this). The only major town is the capital city known as “Andorra la Vella.” Interestingly, Andorra was a poor country until after World War II when it became more of a skiing tourist spot. There are seven urbanized valleys that form separate political districts in this country, which are also known as “parishes.” Andorra is not a member of the European Union, but still has an adequate relationship with it and uses the Euro. It has a population of only 82,000 and the official language is Catalan, but Spanish, French, and Portuguese are also commonly spoken here. There are many public and pristine swimming pools and gyms that are free or of low cost and used often by the young and old because regular exercise appears to be one of the secrets to longevity in this country. Andorra is located in the Pyrenees Mountains (Tour De France region) where the air is clean. A mountainous country also translates into an area replete with hiking and biking trials. The diet consists of a classic Mediterranean type fare with lean meat, red wine (even served in the hospitals), fish (trout is local and popular), vegetables, and olive oil. One of the most common winter dishes is “escudella,” which is a soup of veal, chicken, potatoes, and vegetables. Socialization is another key component in this country and in the Mediterranean diet. There are leisure centers that are free in every parish of Andorra and tight family and friend connections are the rule not the exception.

Andorra also enjoys a fabulous health care service for its population, and it is not unusual for folks to have a surgery even in their 80s and even 90s. Andorra also enjoys a safe water supply, and sanitation is available to 100 % of the population in the rural and more urbanized areas. Andorra also enjoys 100 % employment and literacy, and minimal to no crime (one prison with approximately 50 inmates) which are also factors in health and longevity. Thus, stress appears to be very low in this country. Some government officials also credit the lack of long-term stress to the fact that there has been 700 years of peace in this country. Seven centuries without major conflict is unique. Yet there is also little concern about natural disasters since avalanches are the only real natural threat to life. Tourism accounts for about 80 % of the income and the banking sector is also formidable in this wealthy country. So, it is a smart, small, wealthy, and healthy country.

So, how long is the average life expectancy? It is 83.5 years, but for the women in this country it is about 85 years and for men about 81 years. Now, there is something really interesting that is often not reported in stories about this country perhaps because it puts a slight stigma of the perception of health in Andorra. The fact is that there are still many Andorrans that smoke. Tobacco is still one of the only agricultural resources in this country. It appears to be the sum of what one does for their health compared to anything else. The reason this is fascinating is that in many countries such as Canada and the USA smoking is associated with many bad behaviors (unhealthy diet, lack of exercise, excessive drinking, …), but not necessarily in Andorra. It is the opposite for many folks that live here. Still, this is no endorsement for smoking, just the opposite. It is argued that the male life expectancy in this country would approach that of females if more men quit smoking because less women compared to men in this country are smokers. Regardless, Andorra is number 1 so to speak in the race for more quantity and probably quality of life. Still, any country that is envied for its health can run into trouble because tourism, fast food, and other stressful and unhealthy behaviors can suddenly emerge, which is what has happened recently to Okinawa, Japan and what is also potentially threatening Andorra. So, whether or not 10 years from now this country will be number 1 in terms of longevity will be interesting. And the last point to grasp from visiting this country and speaking with health care professionals—the use of dietary supplements (even prescription medications) does not appear to be prevalent among them, which is also apparently the case for most of the longest-lived populations. The mantra of only utilizing a pill when truly needed seems to be the rule and not the exception. Again, the foundation of longevity and quality of life revolves around simple or basic rules, which are not easy to follow and not easy to adhere to on a regular basis.

On December 10, 2013, the EFSA (European Food Safety Authority based in Parma, Italy) announced their investigation of aspartame (the artificial sweetener) and found that it was safe for human consumption [20]. “This opinion represents one of the most comprehensive risk assessments of aspartame ever undertaken” said the Chair of the EFSA’s Panel Dr. Alicja Mortensen. A can of diet soda contains 180 mg of aspartame, which means an adult weighing 75 kg would need to drink more than 16 cans per day to exceed the EU acceptable daily intake level (EU level is 40 mg/kg of body weight and the US level is 50 mg/kg). Artificial sweeteners are easy targets but in reality they are not absorbed by the body and cause minimal blood sugar or insulin shifts and in the case of aspartame it consists of two amino acids (aspartic acid and phenylalanine). On the other hand, if someone believes they can consume seven diet sodas a day this type of overall lifestyle that encourages this kind of soda consumption will not be healthy. Someone that drinks too much soda also tends to have other unhealthy behaviors and a lack of good nutrition.

Artificial sweeteners (AS) are used in individuals with the common goals of losing weight, maintaining a healthy weight or reducing sugar intake. More clinical research or studies are always needed to determine the impact of these compounds on human health. Yet on a regular basis there appears a publication that promotes fear in many and rarely objective education when paraphrased for the public. For example, a series of laboratory experiments and observational data was utilized by a group of researchers to determine the impact of saccharin, sucralose, or aspartame added to the drinking water of lean 10-week-old mice [21]. Testing with antibiotics and transference of the flora were also achieved in animals. A small interventional and larger observational study of human consumption of AS was also conducted. AS mouse groups developed glucose intolerance (p < 0.001) and this did not occur in the mice consuming water, glucose and sucrose. Fecal transplant of the flora changes into non-AS consuming mice replicated the glucose intolerance phenotype (p < 0.004). Levels of glycosylated hemoglobin were significantly increased (p < 0.002) when comparing a subgroup of high AS consumers (40 individuals) compared to non-AS consumers (236 individuals). Researchers also followed seven healthy volunteers for a separate study where they consumed the FDA maximum acceptable daily intake of saccharin, and four of these individuals developed significantly poor glycemic response on 5–7 days after AS consumption versus days 1–4 (p < 0.001). AS appeared to alter friendly flora that could deter morbidity. An acceptable daily intake of saccharin is from the FDA is 45 packets per day [22]. And remember that saccharin was associated with the development of bladder cancer in laboratory rats in the 1970s, and since that time 30 human studies found the rat studies were not of significance (mechanism of action did not exist and/or high exposure to numerous items cause bladder cancer including vitamin C in these animals) to humans and in the year 2000 saccharin was removed from the potential carcinogen list [22, 23]. Additionally, the authors of the past observational study found glucose issues in the 40 “high-dose” AS users [21]. How high was this amount precisely, and what other unhealthy behaviors did these 40 individuals harbor? This was not answered.

At the same time I do not like the fact that AS causes changes in intestinal flora but this should not be the surprising part. The surprising part is that if these primarily animal studies are correct that in some individuals these flora changes may be associated with unhealthy changes. Yet most troubling in all of this preliminary and mostly animal based research is the hysteria this kind of story is able to generate and the deviation or distraction from real immediate health issues this stories have on society and individuals. AS alone have never shown consistent or significant clinical weight loss (just statistically significant) in individuals that switch to them except in some randomized trials there has been extremely modest or weak weight reduction, but in reality they occupy a position as part of a comprehensive weight loss regimens that allows some select individuals to lose weight [24]. In fact, arguably, one of the most comprehensive meta-analysis of AS examined 15 randomized trials and nine prospective studies and found significant reductions in weight parameters in the randomized trials, which included −0.80 kg (1.5–2 pounds) of body weight, −0.24 in BMI, and −0.83 cm (one-third of an inch) for waist circumference. Among prospective studies there were no beneficial effects except for a slight increase in BMI (+0.03) with AS [25].

There has been no benefit in terms of intramuscular B12 injections versus low-cost supplementation (for hematologic and neurologic responses) and no improvement demonstrated in fatigue in cancer patients (unless of course symptomatic macrocytic anemia from overt B12 deficiency) and this could save substantial health care dollars if this was implemented [26, 27].

Additionally, there has been concern that excessive dosages of supplemental high-dose B vitamins could theoretically increase the growth of some tumors including breast cancer, but it appears the more convincing data is in the area of colorectal cancer. Folate is needed for DNA synthesis and methylation, which are also important to cancer initiation and proliferation. Yet some believe that dietary folic acid and perhaps B12 are important as a cancer preventive, but once cancer occurs it could encourage cancer growth. In breast cancer currently there is some evidence from meta-analysis to suggest that dietary (not supplemental) folic acid is a breast cancer preventive in women that consume alcohol [28]. And arguably the largest review of data on 50,000 individuals from 13 randomized trials demonstrated no risk of cancer for treatment for at least 5 years of folic acid supplementation [29]. And the one trial that is receiving the most attention that for most women high-dose B-vitamin supplementation is safe is the WAFACS (Women’s Antioxidant and Folic Acid Cardiovascular) study, which was a randomized, double-blind, placebo-controlled trial including over 5400 female health care professionals 40 years or older with preexisting cardiovascular disease or three or more cardiovascular disease risk factors. Participants were randomly assigned to 2.5 mg of folic acid, 50 mg of vitamin B-6, and 1 mg/day of B12 (all mega-doses of these B-vitamins) and after an average of 7.3 years there was 34 % significantly lower risk of age-related macular degeneration (p = 0.02), and no increased risk of cancer including breast cancer, and no impact on cardiovascular risk or mortality [30, 31]. Longer observations may be needed but at least this provides some initial comfort. What was not mentioned or seemed far more alarming in this US trial of health care professionals is that the average BMI was over 30 (obese), which should be more concerning compared to high-dose B-vitamins for health. Still, there is some preliminary evidence to suggest that in high-risk breast cancer individuals the use of folic acid supplements could increase the risk of disease or recurrence, but if this risk even exists it may be small since overall folic acid supplementation has not been correlated with overall prognosis [32–34].

Most recently, the B-PROOF (B-vitamins for the Prevention of Osteoporotic Fractures) concluded and found no overall benefit (subgroup above 80 years old showed a 73 % lower osteoporotic fracture risk) when taking 500 μg of B12 and 400 μg of folic acid in individuals with elevated homocysteine (12–50 μmol/L) for 2 years [35]. However, 63 versus 42 participants in the B-vitamin group versus placebo reported cancer diagnosis (56 % increase). The three cancers with the largest numerical cancer case difference was colorectal cancer, other gastrointestinal cancers (14 versus 5, 7 versus 1, and breast cancer 7 versus 3). The curves for cancer incidence in this trial began to separate shortly after the B-vitamins were utilized and more noticeable in elderly (greater than 80 years).

There is no known impact of beet root juice on breast cancer but it is one of the largest dietary sources of inorganic nitrate that may be converted to nitric oxide (NO) by flora, and it could improve athletic performance and slightly lower blood pressure from some clinical trials [36]. My biggest concern with this fad is the caloric content of drinking more than a cup a day. Otherwise this is interesting.

Individual beta-carotene supplements have been found to increase the risk of lung cancer in current smokers from two past notable trials (ATBC used 20 mg and CARET used 30 mg/day) and should not even be used in patients who are former smokers based on preliminary evidence from the AREDS2 trial [37–40]. The amount in a single dose standard multivitamin is not the issue and neither is the amount in food. Only these larger amounts were associated with lung cancer risk. There has been no impact of these supplements on breast cancer (no increased or decreased risk).

A quick review here is needed for clarity. It was one of the most surprising findings in a large dietary supplements study ever recorded when in the 1990s the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) trial , a randomized study of 50 mg of alpha-tocopherol and/or 20 mg of beta-carotene on over 29,000 male chronic smokers was stopped [37]. Participants receiving beta-carotene had a significant increase in the risk of lung cancer and of dying from all causes compared to placebo. Yet soon after the ATBC stopped, the Carotene and Retinol Efficacy (CARET) Trial , a randomized study of 30 mg of beta-carotene and 25,000 IU retinol for individuals with a history of smoking or asbestos exposure was also stopped for precisely the same reasons as ATBC [38]. A significant increase in lung cancer diagnoses and overall mortality occurred in the supplement versus the placebo arm. The third large prevention trial of beta-carotene, the Physicians’ Health Study (PHS) , did not show anything positive or negative, but PHS was not just conducted in smokers and it appears the median blood levels of beta-carotene (50 mg every other day) from supplementation were far lower in the PHS compared to the two other trials (1.2 μg/ml versus 3.0 μg/ml in ATBC and 2.1 μg/ml in CARET) [40]. In other words, researchers received a real indication that an excess of certain dietary supplements or antioxidants in certain populations could potentially increase the risk of cancer and early death. This was again a substantial change in the paradigm of thinking that really impacted present and future thoughts and beliefs and also suggested that similar to drug trials, large phase-3-like supplement trials need to have some phase I and II evidence before moving to a phase-3 trial that could be costly in dollars and in terms of morbidity and mortality without adequate preliminary evidence.

More recently, the result of one of the largest eye health studies in the world (conducted in the USA) was released. Interestingly, there was 15 mg of beta-carotene in the multivitamin type supplement that they used in this clinical trial. It was found that former smokers that took the supplement daily with the 15 mg of beta-carotene had a significantly higher risk of lung cancer (23 cases versus 11 cases) compared to those that did not take the supplement with beta-carotene [39]. This is not proof that beta-carotene in dietary supplements can increase the risk of lung cancer in former smokers, but we already know that it can do this in current and perhaps former smokers. Thus, former and current smokers need to try and eliminate beta-carotene in their dietary supplements going forward. It is not worth the risk—first do no harm. Dietary sources of beta-carotene include: carrots, sweet potatoes, spinach, collards, kale, cabbage, …. Many multivitamins have reduced their beta-carotene or eliminated it from their product but there are still many with it, so ask patients that are former and current smokers to check the dosage.

This is a common phrase utilized to market a supplement to patients. And when approaching it superficially it does appear to make sense. Why not boost my immune system to prevent disease or fight cancer? For example, colds and the Flu are really called “cytokine diseases ”—which means cytokines are protein molecules that the immune system makes when you are infected by a cold virus, and the cytokines travel to the site of the infection where they make sure an immune response occurs to the virus, but these pro-inflammatory cytokines are the reason for the symptoms you experience (not the virus itself) [1]. In other words, the body’s response to the virus is what causes the symptoms. It is an over reacting immune system in a body that has never dealt with a strong virus like the flu that was part of the reason there are so many deaths from the flu. And the impact of the flu allows for other infections to take hold and cause pneumonia. So supplements that claim they can really “enhance your immune system” or “boosts the immune system” is something that appears to make sense but does not. Clinical efficacy is what matters. Weak or strong immune systems are just as likely to get a cold, and what is needed is better immune surveillance or modulation. Autoimmune diseases from rheumatoid arthritis to Crohn’s to Celiac to Lupus to Allergies (food and otherwise) are immune systems that are “boosted.” In other words, the body is being attacked by the immune system and this is why some immune boosting drugs for advanced cancer have can result in serious autoimmune toxic events (diarrhea, hepatotoxicity, colitis, renal, neurologic, ocular issues, …) [41], but in this case (metastatic melanoma) the benefit outweighs the risk. Otherwise the risk exceeds the benefit.

There are two types of adipose tissue that exists in the human body (BAT and WAT) [42]. WAT is the primary energy storage fat and the one correlated with inflammation and obesity. BAT is believed to be protective against weight gain and functions as an energy emitting area, which could reduce weight gain and functions as a glucose sponge (so to speak) in reducing glucose utilization from cancerous and other tissue (this last portion is a theory). Regardless one of the largest US retrospective studies included 98 cases of breast cancer with BAT (from PET CT scans, median age was 46 years) found the potential for women with advanced stages of breast cancer to have a greater survival benefit in those with more BAT.

It is obviously not possible to be an authority on every subject, or to be informed full-time on most issues in a discipline unless working and operating full-time in that specialty. For example, I follow the dietary supplement research daily and know the research occurring in the next 2–3 years because of the unlimited access to this field and the experts and meetings in this category of medicine. Still, after my experience and research I always check in to see what some of the real experts in the field are pondering in order to ensure my opinion is fair and balanced. It is for this reason that when one reads a major study you should be careful not to react to quickly or not read it at all, because there is always a story behind the story and one way to get an objective glimpse is to read any editorial in the same issue of the medical journal as the groundbreaking study. Why? The guest editorial column is usually written by the objective expert not involved in the study but still working full-time in the subject area, and this can transfer general knowledge in the field and how the study is similar or different to past research and how it may impact medical practice. If more consumers and health care professionals read the editorial in the journal instead of the study it would provide more objectivity. For example, when the headlining results of the NPC (Nutritional Prevention of Cancer) were published on December 25, 1996 in the Journal of the American Medical Association there seemed to be a palpable excitement because the trial suggested that selenium supplements were preventing all forms of major cancers, especially prostate cancer [43]. This ultimately led to a clinical trial (SELECT ) that cost taxpayers at approximately 125+ million dollars to test this theory (which failed). If most consumers and health care professionals would have read the Editorial in the same issue only a few pages away by Dr. Colditz from Harvard (and just two pages in length) they would have learned about all the positives of this selenium study and also the many limitations in the study and made strong arguments of why one should not rush to judgment to assume selenium was working and more studies were needed [44]. He ended the editorial in the following way “For now, it is premature to change individual behavior, to market specific selenium supplements, or to modify public health recommendations based on the results of this one randomized trial.” Fast forward 10–15 years later and he was 100 % correct and these supplements not only did not prevent cancer, including prostate cancer, but may actually have increased the risk of skin cancer returning in those previously treated for skin cancer, increased the risk of type 2 diabetes at the same dosage (200 μg daily), and arguably increased the risk of mortality from prostate cancer from more recent clinical data, and increase the risk of aggressive prostate cancer in those patients in the phase 3 SELECT trial already replete from dietary selenium [45–49].

Finding a credible expert that writes an objective editorial can be found from numerous sources and at times in addition to a medical journal despite journals being some of the best overall sources. When one of the largest randomized studies was published in the New England Journal of Medicine that showed such a large difference in favor of the Mediterranean diet (PREDIMED Study) over a reduced or low-fat diet [50], of course there was palpable verve. Dr. Dean Ornish (right or wrong, agree or disagree he changed the world for the better arguably by researching and promoting lifestyle to prevent disease long before it was proper to do so) provided a critical and primarily objective analysis [51]. In the PREDIMED study , total fat ingestion in the reduced fat group was reduced insignificantly from 39 % to 37 % (only 2 %-low-fat?), so in reality the PREDIMED Mediterranean diet with free access to extra-virgin olive oil (1 L/week) and nuts (30 g of mixed nuts per day-15 g of walnuts, 7.5 g of hazelnuts, and 7.5 g of almonds) and other changes was compared to no major dietary fat change. For example, the American Heart Association definition of low fat is less than 30 % fat and the Dr. Ornish diet is less than 10 % fat. Yet some physician experts quickly heralded this trial as evidence for why the Mediterranean diet trumps low-fat diets. This was reactionary, not objective and not a personal extensive review of the study which also contained numerous appendix data information that was evaluated by those that wrote the editorial in the journal and otherwise [51, 52]. What also appeared to be missed was the potential conflict of interest some of the primary researchers appeared to have with some companies or nutrition boards because this study was only about diet—calories intakes were not to be reduced, nor was exercise promoted.

It could also be argued that in the past had more individuals read the editorial to the once notable Lyon Diet Heart Study , one of the first randomized trials on the Mediterranean diet, they would have realized that the researchers used a canola oil based margarine in the diet plan (not just olive oil) and it appeared to work very well [53, 54]. The Lyon Diet Heart Study (initially published in the journal Lancet in 1994) was a randomized single blind secondary prevention trial for patients that suffered from a first myocardial infarction. Patients were randomized to the intervention/Mediterranean diet high in alpha-linolenic acid or ALA (from canola oil margarine) (n = 302) or control group (n = 303) for what was supposed to be 5 years. The ALA diet consisted of significantly less saturated fat, cholesterol, and linoleic acid but greater intakes of oleic and ALA confirmed by plasma measurements. Serum lipids, blood pressure and BMI continued to be similar in the two groups. After a mean of just 27 months, the trial was terminated by the Scientific and Ethics committee due to a 70 % reduction in dying from any cause primarily due to a dramatic reduction in heart disease deaths in the Mediterranean diet group. There were three cardiac deaths and five nonfatal myocardial infarctions in the intervention (ALA) group versus 16 and 17 in the control group (73 % reduction in risk from these two main endpoints, p = 0.001). Overall mortality was 8 in the Mediterranean diet group and 20 in the control (70 % reduction, p = 0.02). The conclusion of this unique randomized trial at the time was the following: “An alpha-linolenic acid-rich Mediterranean diet seems to be more efficient than presently used diets in the secondary prevention of coronary events and death.” The final report, published in the journal Circulation was even more surprising when following some of the participants for longer periods (almost 4 years) of time and included a 65 % reduction in cardiac deaths, 66 % reduction in deaths from all causes and a potential reduction in cancer risk in the Mediterranean canola oil ALA diet group [55, 56]. Researchers attempted to examine blood fatty acid markers from the diet that could predict prognosis and “only alpha-linolenic acid was significantly associated with an improved prognosis” and not other fatty acids [55]. This is not to advocate or imply that canola oil was the only reason for success but it appeared to be one of the primary reasons. Still, this was one of the first studies to lead to the excitement over the Mediterranean diet and olive oil, but the reason the Mediterranean diet group had such large improvements in their plant omega-3 levels is due to the fact that they and their family were given a supply of canola-rich margarine to use for the whole study (like the PREDIMED study and free olive oil or nuts). The researchers were concerned that the participants would not adhere to the diet if the only oil they could utilize were olive oil. So, they included a commercialized canola oil margarine from France (Astra-Calve, Paris, France), which again could have been one of the biggest reasons for the success of the Mediterranean diet in one of the most famous diet studies or at least Mediterranean diet studies. Interestingly, mean BMI on the last recorded visit of the study was 26.3 with the Mediterranean diet versus 26.9 with control (in more recent PREDIMED BMI was 30 and waist circumference was 100 cm—both would classify as obese) and LDL was 4.17 mmol/L (161 mg/dl) versus 4.23 (163 mg/dl), and caloric intake was −141 calories significantly less for the Mediterranean diet. Other significant differences were the following: higher fiber intakes, lower cholesterol intake, higher alpha-linolenic, and higher oleic acid with the Mediterranean diet but again it appeared only alpha-linolenic acid levels correlated with an improved prognosis. So, while “experts” still tout olive oil (with conflicts of interest) few experts appear to realize that canola oil arguably helped spur the sales of olive oil for health benefits based on this groundbreaking study where some thought the only oil used must have been olive oil. Perhaps this is why the editorial provided in the updated Lyon Diet Heart Study commented that few cardiac health care professionals at the time appeared to know about this study [55], and arguably today this statement is still true but includes many in the public that advocate for only olive oil in a Mediterranean diet as a path to success. The issue is that evidence-based medicine is suggesting that canola oil should be or should have arguably continued to be a major part of Mediterranean diet randomized trials but somehow this did not continue to occur. Canola oil is a primary product of Canada so is this some form of a Mediterranean diet country specific conspiracy? Spain for example appears to produce almost half of the world’s olive oil supply. The real issue actually is the lack of reference or even deference to the Lyon Diet Heart Study, especially for all the websites that try to convince consumers that canola oil is harmful from a laboratory study or processing stand point (not a randomized trial).

This is a common term I utilize in lectures and with patients to explain that cancer treatment is based on probability with no guarantee. Patients generally choose the treatments with the higher probability of success and clinicians are generally supposed to proffer options with higher probability or success rates. Some forms of alternative (and at times conventional) treatments focus on lower probability or a rare treatment success but do not refer to the greater research. This is tantamount to casino or lottery advertising that suggests one person has to win so why not you, and the evidence-based answer to that question is because I almost have a probability of winning that is arguably similar to the probability of not playing the game. The primary reason most humans do what they do is based on probability of an event or something they hope to achieve in making a choice, for example putting on a seatbelt to reduce the risk of receiving a ticket, injury, or death. How about stepping on an airplane, bus or train because it is rare to be in a catastrophic event in these scenarios (otherwise few individuals would utilize them). Most activities are preformed based on a probability-based event whose outcome is assumed will be achieved (not a guarantee). This is why personal testimonials are so powerful in convincing someone to do something without overt research because it distracts a patient from the fact that there is no credible research. When consulting with patients it should be mentioned how many websites promoting chelation utilize primarily testimonials but rarely high methodology research (because it does not exist). Patients should be warned about lottery effect advertising with certain pills and procedures that could cost desperate individuals and families a fortune by certainly offering a temporary dash of hope, but with a potential pound of permanent disappointment.

Chelation to reduce compounds in the body that have truly been demonstrated to be harmful is one part of conventional medicine and this should be mentioned to patients; however, chelation therapy to promote cancer treatment by reducing “toxins” is another entirely separate non-evidence-based program that can be costly to susceptible cancer patients and compromise the window of opportunity for more evidence-based treatments. For example, iron overload and chelation could be utilized in myelodysplastic syndromes (or even thalassemia ) and is not uncommon [57, 58], but iron overload or mercury overload chelation to treat breast cancer has no credible evidence but has a considerably personal detrimental cost. Again, chelation therapy is utilized in certain areas of cancer to reduce toxicity but it is currently not utilized to profoundly impact prognosis, especially in breast cancer. This does not imply that in the future there will be no role, but that currently it is advertised to many patients using the tactics of casino or lottery based advertising (plenty or personal testimonials and no evidence-based research).

Patients need to be informed about the difference between clinical significance and statistical significance. If cholesterol is statistically lowered or favorably changed with an agent but the clinical endpoints or outcomes do not change for the better then what is the point of using the treatment? For example, this is currently what niacin is suffering from in medicine [59]. Almost all clinically significant medicines (including some integrative) demonstrate statistical significance but the reverse is not always the case.

Coconut water could be higher in potassium compared to a banana in some cases, and it is generally low in calories with some sugar, but coconut oil is different [1]. It is primarily saturated fat, which can increase your good cholesterol (HDL) but it can also increase your bad cholesterol (LDL) . Coconut oil contains large amounts of the saturated fat known as “lauric acid ” and this is what could also increase good cholesterol. Coconut oil could be utilized in diet after a baseline cholesterol examination to determine the eventual impact of the oil. Eggs do not cause significant increases in cholesterol as once thought. Eggs are low in calories (70–80 calories each), one of the best sources of high-quality protein (muscle support and to suppress appetite), one of the only natural sources of vitamin D, a natural source of choline that may improve brain health or memory, and is a large source of two compounds (lutein and zeaxanthin) that are being used as pills in clinical trials to potentially preserve eyesight from macular degeneration, which is one of the leading causes of vision loss in the world. And the cholesterol content of eggs continues to decrease over time thanks to more efficient farming methods. Both the egg white (main protein source, 15–20 calories) and the yellow part of the egg (choline, vitamin D, mineral, and eye health compound source) have value.

However, there are some rare situations where a few eggs a week can increase bad cholesterol or LDL. There have been only a few preliminary studies of coconut oil , for example at 30 ml a day to reduce body fat for 3 months in abdominally obese women and there was a statistically significant waist reduction but not clinically significant (0.5 in.) [60]. Still, coconut oil has been utilized regularly with a ketogenic diet (along with palm kernel oil) and this is the point. It appears the greatest flexibility with diet occurs in women and men that were able to achieve the goals set in Chap. 3 after normalization of LDL, glucose, blood pressure, and weight via exercise and caloric control whether or not it involves the rest of these selective items (chocolate or eggs) become less of a concern. These items should be consumed on a regular basis if desired (which is the point of this paragraph and could be utilized in patient consults) if one is able to achieve clinically significant results when dieting with them as part of a comprehensive effective program or after achieving weight loss results and then deciding to incorporate them in the diet.

CoQ10 arguably receives most of its attention for the potential to reduce statin-induced myalgia (SIM) or blood pressure reduction, but the data on the benefit has been mixed—not consistent [1]. Additionally, there is some indirect evidence to suggest CoQ10 could increase bleeding risk in patients on antiplatelet medicines such as aspirin and clopidogrel, but it could also harbor vitamin K like effects and could reduce the efficacy of warfarin [61]. Overall, and in large randomized trials thus far the side effects overall have been similar to placebo, but the results have been disappointing. For example, a phase 3 randomized, placebo-controlled, double-blind clinical trial known as “QE3” (Coenzyme Q10 in Early Parkinson Disease) was conducted at 67 North American sites [62]. This trial compared placebo to 1200 mg/day, or 2400 mg/day CoQ10 (all participants also received 1200 IU/day vitamin E). The withdrawal rate was only 2.0–2.5 % among the groups and no clinical benefit was demonstrated over placebo. There were also no significant differences among groups in any laboratory parameter, vital signs or in EKG measures. Hypertension (2.6–3.5 % versus 0 %) and insomnia (3.1–6.5 % versus 3.0 %) were documented more often in the CoQ10 groups but the overall incidence was low.

CoQ10 currently holds no role in breast cancer but the data is limited. A randomized trial of 236 women with newly diagnosed breast cancer and planned adjuvant chemotherapy were randomized to 300 mg of Co10 or placebo and each group received 300 IU of vitamin E (all pills divided into three daily doses) [63]. Treatment was continued for 24 weeks and there was no difference in fatigue (the primary endpoint) or in the secondary endpoints of depression or quality of life scores. The goal of the trial was to prevent or reduce fatigue in patients and it was not able to accomplish this task. Regardless, side effects were similar to placebo. This is a costly supplement overall and unless there is future research with statins and CoQ10 (see Chap. 4) for side effect reduction there appears to be otherwise no role for CoQ10 supplementation currently in breast cancer.

Colon cleansing (high colonics or colon hydrotherapy ) enema or cleansers where fluids are introduced through a tube inserted into the rectum could alter beneficial flora, perforate or injury the colon, cause hyponatremia, sepsis and become a medical emergency [64–68]. It is interesting that perforating the colon during a colonoscopy is rare but a real concern for some individuals but perforating the colon with an unregulated alternative treatment involves far more risk and has not prevented cancer or saved lives like a colonoscopy [69]. The ideal colon cleanse should be the incorporation of regular fiber intakes for overall health benefits and to establish and healthy microbiome or gut flora [1]. Fiber is arguably one of the best prebiotic sources available in medicine today, which have the ability to reduce the need for more pills such as probiotics (see Chap. 3). Dietary fiber should be the first source but supplemental options can also be helpful and now have an abundance of clinical research [70].

Increasing antibiotic resistance to multiple disease causing bugs are concerning. Other non-antibiotic options are needed as potential alternatives. Cranberry drink and supplements have garnered some interest as a potential viable option for recurrent UTIs, but longer duration trials are needed to provide more objective evaluations of supplements versus certain drugs. A double-blind trial of 221 premenopausal women that were randomized to a 12-month utilization of TMP-SMX 480 mg once daily, or 500 mg twice daily of cranberry capsules was published [71]. After 12 months the average number of participants with at least one symptomatic UTI was significantly reduced in the TMP-SMX group (1.8 versus 4.0) and the percentage of women with at least one symptomatic UTI was higher in the cranberry group (78 % versus 71 %). Median time to first UTI was 8 months on the antibiotic compared to 4 months with cranberry. Approximately 91 % of the asymptomatic specimens tested were TMP-SMX resistant after 1 month compared to 28 % with cranberry. Antibiotic resistance did not increase in the cranberry group. Thus, TMP-SMX at 480 mg/day was more effective than 500 mg twice a day of cranberry capsules to prevent recurrent UTIs in premenopausal women, but at the limitation of causing antibiotic resistance. It is concerning that the antibiotic resistance was so high in such a short period of time (1 month), and a “simultaneous increase” in resistance to other commonly used antibiotics (fluoroquinolones and amoxicillin) also occurred in this study. Antibiotics such as this one are more effective than a supplement and less costly in many cases [72], but when examining the overall risk-versus-benefit ratio some doctors will be more eager to recommend cranberry dietary supplements for some patients, especially since cranberry juice have questionable efficacy [73], and are replete with sugar and calories and arguably can increase weight gain that can also increase recurrent UTIs [3]. Additionally, cranberry supplements (a few calories per pill) have preliminarily been as effective as consuming large volumes of the juice [73]. And cranberry supplements are being studied to prevent urinary infections in patients undergoing cancer treatment [74].

Curcumin appears to be often embellished as a potential adjuvant treatment of cancer, and it lacks adequate clinical trial data to objectively access its potential for efficacy. Still, its potential for treating some side effects of cancer treatment is interesting and appears to have greater promise compared to the treatment of cancer itself. For example, the reduction in radiation dermatitis is preliminary but interesting [75], as is the potential for reducing arthralgia or even cognitive issues [76–79]. Arguably, more positive research in the future would provide more credibility for curcumin to be presented as a potential option for breast cancer patients with joint pain or major depressive disorder (not covered in Chap. 7), but more focused research in this area is still needed.

Indole derivatives or dietary indoles found “naturally” in foods are often touted as supplements that can prevent breast cancer. Indole-3-carbinol (I3C) is also often touted as a breast cancer supplement or in food, which is also converted to DIM, and sulforaphane (indole derived from the hydrolysis of glucosinolates) [1, 80]. So, why not just consume more cabbage, broccoli and Brussels sprouts or just overall more cruciferous vegetables to ideally get all of these compounds from their “natural” source and this is also where most of the positive research is derived from publications that also appear to espouse potential supplementation [80]. Other reasons cruciferous vegetables should be promoted more than the DIM supplementation (and other cruciferous supplements) is not just a cost issue, but lack of clinical research to support short- and long-term issues of supplementation. One small clinical study of 108 mg/day of DIM for just 30 days but with only 19 women (history of early stage breast cancer) completing the trial (ten with DIM and nine with placebo) demonstrated a nonsignificant increase in the 2-OHE1/16alpha-OH1 ratio from 1.46 to 2.14 (p = 0.059) [81], which is tantamount to an interesting effect (since increasing this ratio could lower estrogenic stimulation of breast tissue), but it is a pilot study at best with no phase 1 or 2 or 3 data to support the clinical significance of this finding, and what happens long-term when ingesting this supplement in larger number of participants? Can it increase the risk of breast cancer, have no impact, or reduce the risk? Remember the beta-carotene or selenium information presented earlier in this chapter. All of these trials in cancer were really initiated because of early potentially positive pilot studies from food sources that turned out to be completely incorrect. A recent small study of 20 women with a BRCA1 mutation showed no impact on the 2:16 ratio mentioned earlier over 4–6 weeks with 300 mg DIM versus placebo [82]. And what about the observation that exercise can favorably impact this ratio and exercise is a more definitive risk reducing strategy for breast cancer [83]. Regardless, this ratio change is interesting but it is not a definitive marker of breast cancer risk or recurrence [84], and thus these supplements with such preliminary data such as DIM have to allow patients to address or contemplate the other potential consequence when ingesting them, which is the theoretical potential currently for it to increase, decrease or have no effect on personal risk of breast cancer when ingested long-term and is a person willing to accept that risk?

Aromatherapy essential oils could reduce stress, improve relaxation and sleep, which is why they could also assist with tension headaches for example [85, 86]. In reality it is a form of meditation or stress reducer that can have profound effects. People might not realize that one of the best selling devices for blood pressure reduction (called “RESPeRATE ”) is simply a device that teaches you how to breathe more slowly and deeply and relax and it helps temporarily lower blood pressure, but so do placebo comparative relaxation techniques such as soft music from some of their same clinical trials [87]. Essential oils are an interesting integrative medicine for some specific cancer treatment side effect reduction such as stress/anxiety but also there are greater risks when ingesting any of these oils orally such as the potential for lipoid pneumonia [88]. Thus, aromatherapy and topical treatments appear interesting and safer versus actual oral ingestion.

Ocean Farmed Salmon is not good for you? Ocean-farmed salmon has is now on a prestigious eco-friendly fish list. The Monterey Bay Aquarium Seafood Watch Program is the one many experts and food purchasing companies utilize to decide what types of fish are safe to order and consume for customers [89–91]. Verlasso^® (based in Miami—sold in about 30+ states) farmed salmon from Chile has made the yellow list or a good alternative list. Up until now there were no ocean-based fish farms included on these lists.

It requires 4 pounds of wild fish to produce one pound of farmed salmon! This is because farmed fish are given feed high in omega-3 to thrive such as anchovies and ground-up herring. Now, it takes 2.5–3.5 pounds to produce a pound of salmon, so things are improving. Approximately 20 % of the world’s fish catch (actually 17 %) is now used for fish oil or fishmeal. Verlasso is a company that has now made this prestigious fish list by making some changes including using a genetically modified yeast (GMO-based) omega-3 feed instead of wild caught fish. Verlasso is actually a ^® company involved in a joint venture between AquaChile (raises the salmon) and Dupont (provides the feed). And their ratio is 1.34 (pounds of wild fish) to 1 (pound of farmed salmon), which is one of the best in the industry right now. Some fish are still needed in the feed because salmon are very selective eaters but this is good news for salmon farming because I believe Verlasso will make a lot of money from this and it will force other farmed raised salmons to keep up in order to maintain or increase profitability (similar to what is happening with fast food ingredients and improving quality or what happened to trans-fat). Salmon is now the third most consumed fish in the USA right now behind shrimp and tuna and I still prefer the taste of wild Alaskan salmon but at least some reputable farmed salmon companies. This is critical because the world supply or Alaskan supply of salmon is not large enough to handle global demand so there needs to be other sources of salmon. Perhaps this is the first of many companies that will have another option. And the nutritional profile of some of these farmed salmon do compete well with wild salmon, as do other farmed fish (such as trout), but there is always room for additional improvement from some specific farmed fish sources [92–94].

Probiotics pills sound healthy from all the advertising. What if you could transplant healthy bacteria with feces for some individuals and it would work far better than any other pill at treating or curing the issue? This is already being accomplished. Clostridium difficile (C difficile) is a bacterium infects the intestines and can cause significant recurring morbidity, and it can also be fatal. This infectious agent is also becoming more aggressive over time and even more resistant to most antibiotics. Yet currently fecal transplants (FT, also officially known as FMT or Fecal Microbiota Therapy ) have a current 80–100 % cure rate, which surpasses any other therapy at the moment [95, 96]. The excitement of FT is it is low cost and addresses the reason for the issue (no antibiotic does this) and no serious side effects have been observed. Does it work like a perfect probiotic to colonize or take over an area of the intestine so the bacteria cannot reside, nor does it provide better immune surveillance or both? Researchers do not know, but they do know it is working.

Here is how FT work or are done in general [95, 96]. Donated feces from a healthy donor (feces is screened for infectious organisms) is used and homogenized and placed in the colon. There are three ways it can be given to the patient:

Preliminary research suggests the colorectal route may be even more effective compared to the NG or ND approach. Still, all this research is preliminary and FT can take a week to set up because donors have to be screened. All donors are not only carefully reviewed but again stool tests and blood tests need to be done to make sure the donor has not been exposed to any infectious agents. This is why spouses or life partners are the ideal donors in many cases.

For example, an attention gathering randomized trial of FT was published in the New England Journal of Medicine and was completed at the University of Amsterdam and the study was stopped after interim analysis because of efficacy [96]. Patients received antibiotics (vancomycin) or basically this same regimen and then received fecal donation with a nasoduodenal tube. In the FT group 81 % had resolution of diarrhea after first treatment compared to 20–31 % in the antibiotic alone groups. There were no significant side effect differences between the groups except for mild diarrhea and abdominal cramping on the FT day. This was a small randomized study with only 16 patients in the FT group but the results were quick and noteworthy and patients were found to have “increased bacterial diversity” similar to the healthy donors and the FT.

Interestingly, the biggest barriers to more people being treated with FT (especially if they have a long history of C. difficile) were some physicians not completely understanding the research, data, or methods of this approach [95, 96]. In many situations and surveys it was patient research and commentary that the led the doctor to begin to recommend or offer FT (a lesson for all of medicine when a patient is empowered with objective information). This study and others demonstrate the power of healthy bacteria to occupy the intestinal tract and other research with this same concept for autoimmune disease treatment is just being initiated. This is why I am fixated with healthy diets, weight loss, fiber and other means to improve the immune health of the gut, and why probiotic supplements are interesting but need more research in many areas. My first choice is to change flora with heart healthy lifestyle changes outlined in Chap. 3, but when needed other approaches are looking interesting.

One of the best and more recent studies to address this issue was a clinical trial of 2000 mg/day of garcinia cambogia extract compared to another supplement or placebo in 86 overweight subjects over 10 weeks [97]. The garcinia extract not only caused no significant weight loss or change in percent body fat but there were no effects on cholesterol compared to a placebo. So, despite a few studies suggesting profound weight loss with this supplement and some television channels and companies promoting this supplement the evidence is modest and there are some safety concerns [98, 99]. In the meantime, there is the low-cost type 2 diabetes “natural” (from the French Lilac) generic drug known as “metformin” (see Chap. 6 for discussion and citations) that has already benefited some breast cancer patients in terms of changing metabolic parameters and it is a known heart healthy drug (first do no harm), and it is arguably of a considerably lower cost compared to any weight loss supplement including garcinia. So, garcinia needs more high methodology research, but whether or not this will really occur is the question.

There are few real well-done mega-dose cancer treatment studies in patients that do not have advanced cancer. In a small and randomized study from the 1990s, there was a suggestion that mega-doses of a supplement compared to a recommended daily allowance (RDA) supplement may reduce the risk of non-muscle invasive bladder cancer recurrence after BCG treatment [100]. However, a larger follow-up study was needed to confirm these preliminary findings, which to the researchers credit, occurred [101]. Patients were BCG naïve with carcinoma in situ, Ta or T1 bladder cancer were randomized to receive intravesical BCG or BCG + interferon alpha-2b, and then further randomized to receive an RDA (minimal intake) or mega-dose supplement. Each RDA tablet of vitamins contained 25 % of the recommended daily dose and patients took two tablets twice daily of either the RDA, or the mega-dose supplement. Each mega-dose tablet (again patient four tablets a day throughout the trial) contained: