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FALL 2020 DIGITAL EDITION
ARTICLES
10 18 24
Fasting for Healthy Longevity New Directions for Women in Menopause By: Felice Gersh, M.D.
Gut Hyperpermeability and Autoimmunity By: Julie Beck, DC, MS CSCS
DIM from Cruciferous Vegetables for Men’s Health By: Whitney Crouch, RDN, CLT
ANTI-AGING MEDICAL NEWS | FALL 2020
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Rooted in comprehensive and holistic health, the Fellowship in Anti-Aging, Metabolic and Functional Medicine (FAAMFM) develops forward-thinking practitioners to effectively practice a new form of medicine that is both personalized and preventive. Our fellows are equipped to lead at the forefront of the chronic health crisis with a firm focus on root causes and an extensive array of personalized approaches and strategies. Adaptively designed with you in mind, this fellowship allows practitioners to continue treating patients while gaining the most clinically current education needed to prevent, diagnose, and treat chronic diseases.
Fasting for Healthy Longevity
New Directions for Women in Menopause By: Felice Gersh, M.D.
The following article is not endorsed and/or supported by The American Academy of Anti-Aging Medicine. The purposes of this publication do not imply endorsement and/or support of any author, company or theme related to this article.
Menopause is a universal event for women. The exact age varies somewhat, but the eventual permanent loss of ovarian hormone production is inevitable. Although a natural and “normal” event, the menopausal transition and subsequent years in a menopausal state do not benefit women’s overall health. This is especially true for cardiovascular health. Cardiovascular disease is the number one killer of women in the United States and the risk of a cardiovascular event is directly related to decreasing levels of estrogen as women progress through the menopausal transition. Women who experience menopause early, before age 40, are twice as likely to suffer from a non-fatal heart attack, stroke, or angina before age 60 compared to women who go through menopause at ages 50 or 51, which is the U.S. average.1 They are also more likely to suffer from fatal cardiac events and have an overall lower life expectancy.2 In contrast, women who go through menopause after 10
age 51 have lower rates of cardiovascular disease and enjoy longer life expectancy. Menopause, and the resulting state of permanent estrogen deficiency, is a powerful risk factor for cardiovascular disease that is greatly underappreciated. Loss of estrogen causes systemic vascular inflammation, immune dysregulation, loss of glucose homeostasis, and gut microbiome dysbiosis.3 These dysfunctions set the stage for metabolic disease and ever escalating cardiovascular risk. Typical therapies offered to women to reduce cardiovascular events are pharmaceuticals, such as blood pressure drugs, statins, and diabetes medications. Although pharmaceuticals can be warranted and valuable in certain situations, they don’t access the body’s innate mechanisms to maintain metabolic homeostasis and don’t address the multitude of dysfunctions developing in the menopausal female body.
ANTI-AGING MEDICAL NEWS | FALL 2020
Fasting for Healthy Longevity – New Directions for Women in Menopause
Hormone therapy is also available, but the FDA does not yet recognize or endorse the use of hormones in women to reduce cardiovascular risk. This is despite a substantial body of science supporting the beneficial impact of hormones on the cardiovascular system.4 However, even if the implementation of bio-identical hormones becomes routine for women transitioning into menopause and thereafter, the reality is that we cannot yet administer hormones in a way that replicates the complex hormonal levels and rhythms of a healthy 25-year old woman. Too many women, including those who use hormones, suffer from cardiometabolic diseases. Fasting has been an integral part of the human experience since the beginning of our species and plays a significant role in many religions and societies. Simply put, fasting is any time one is not eating. There are several variations that are associated with different health benefits. “Time-restricted eating” refers to an extended and habitual overnight fast lasting 12 or more hours. When a person fasts for 16 to 24 hours, that is called “intermittent fasting.” If a person fasts for a few days up to a week, that is labeled “periodic or prolonged fasting.” Women in the menopausal transition and up to around age 65 years can gain significant health benefits from all forms of fasting. Combining time-restricted eating with a regular program of periodic fasting is likely the most advantageous combination Time-restricted eating is the easiest form of fasting because the majority of the fast
coincides with time spent sleeping. This is, in fact, why it is so beneficial. Overnight fasting bolsters circadian rhythm in both pre-clinical studies and human observational studies. As with all creatures, humans are governed by time. We have a master clock in our brain that sits atop the optic nerve and senses light and dark, plus nutrients, to track the 24-hour day. Throughout our bodies, we have clock genes that govern most metabolic functions, and these peripheral clocks, in alignment with the master clock, keep all the organs of the body working in beautiful synergy. Unfortunately for menopausal women, estrogen plays a major role in the proper functioning of the master clock.5 As menopause progresses and estrogen production declines, women succumb to circadian rhythm dysfunction, essentially a state of perpetual jetlag that substantially increases risk for diabetes, heart attacks, weight gain, insomnia, cancers, and mood disorders. Time-restricted eating utilizes the power of the peripheral clock genes to reset the clocks in the organs and maintain the synergy that the master clock promotes. By eating at regular fixed times, the body can re-establish metabolic unity and harmony and prevent weight gain and metabolic disruption as seen in clinical and pre-clinical studies10,11 Time-restricted eating can be easily paired with caloric timing—eating more calories earlier in the day and fewer in the evening. Clinical studies have shown that the body is more receptive to food in the morning when insulin sensitivity is high. During a morning meal, glucose enters cells readily and insulin levels
ANTI-AGING MEDICAL NEWS | FALL 2020
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Fasting for Healthy Longevity – New Directions for Women in Menopause
rise only minimally, which reduces weight gain, lowers the risk of diabetes, and contributes to metabolic synchrony.9
transform, seemingly without cause, from the sexy, curvy look of their reproductive years to the matronly look of the menopause years.
If a woman in menopause eats a large, healthy breakfast, a moderate lunch, and a very light, early dinner, and if she fasts every night for approximately 13 hours, she can avert circadian rhythm dysfunction.
Intermittent fasting effectively addresses this problem of fat accumulation. Unfortunately, such a diet plan is extremely challenging, and few women can maintain such a rigid fasting regimen over months and years.
Intermittent fasting refers to 16 to 24h fast. In the common 5:2 intermittent fasting diet, participants fast or eat fewer than 500 calories for two non-consecutive days every week and eat normally on the other five days. Data shows that such fasting is especially helpful for weight loss. Not consuming any calories or eating fewer than 500 calories for two days a week is associated with significant weight loss over time, and for women carrying extra pounds, the benefits can be quite substantial.
Periodic or prolonged fasting, a fast that lasts three to seven days, done about three times per year, offers comparable weight loss benefits to intermittent fasting without the demanding every-week schedule.
Weight gain is extraordinarily common in peri- and post-menopausal women. When estrogen levels plummet, the body’s ability to transport glucose into cells declines and the capacity to burn fat for energy decreases. This causes the body to rely on inflammatory metabolic processes to store excess energy as visceral fat in the abdominal cavity. Visceral fat gives women the dreaded “apple shape” and is a sign of metabolic dysfunction. Because these abdominal fat deposits are themselves inflammatory, they also contribute to increasing metabolic in a vicious spiral of ever-increasing inflammation and weight gain. In addition to damaging health, these fat deposits can damage women’s confidence and sense of self. Women watch their bodies 12
Most people can’t, and really shouldn’t, undergo a multi-day water fast, but fortunately, there is a variation of periodic/prolonged fasting that is safe and effective for most people—the fasting mimicking diet. Certain foods, sometimes called stealth foods, can provide nutrition without triggering the body’s nutrient sensors. If a person eats small amounts of these stealth foods for several days, her body will think that she is fasting. She will get all of the amazing benefits of periodic fasting, but she won’t experience the physical stress and discomfort of actually fasting. Additionally, she won’t lose muscle mass, which is a risk of a true water fast and is very detrimental for menopausal women. The fasting mimicking diet is a five-day researched diet plan that mimics a four-day water fast. It was developed at the University of Southern California’s Longevity Institute under the directorship of Professor Valter Longo. I collaborated with Professor Longo at the time the diet was being formulated, and currently, I am on the speaker’s
ANTI-AGING MEDICAL NEWS | FALL 2020
Fasting for Healthy Longevity – New Directions for Women in Menopause
bureau for the company it spawned. The fasting mimicking diet is an innovative concept for menopausal women because data supports that periodic/prolonged fasting is a beneficial form of fasting for long term health and vitality. Certain cellular functions can only be activated by a longer fast. Pre-clinical studies have confirmed that healthy cells undergo a process called autophagy, a powerful form of cellular rejuvenation. These cells breakdown their internal components, called organelles, and reconfigure them into new organelles, thereby rejuvenating the organs they comprise.6 Studies show that when people follow the fasting mimicking diet once a month for three months, they lose body weight, trunk, and total body fat; lowered systolic BP; and reduced IGF-1. 8 Every woman must transition through and into menopause, a state that may encompass a full half of her lifespan. Menopause, marked by permanent estrogen deficiency, is complex and the impacts on a woman are chronic and body-wide. Treatments must likewise be
REFERENCES
multifaceted and aimed at the root causes of a woman’s symptoms. Pharmaceuticals may have their place, but they don’t address underlying metabolic dysfunction. Bioidentical hormones are beneficial when given properly, but we cannot create the fluctuating hormonal rhythms and levels seen in naturally menstruating women. Lifestyle—sleep, diet, exercise, and mindfulness—is a critical component of any health plan. It’s time for fasting to take its place as an additional powerful therapeutic for menopausal wellness. In my practice, combining time-restricted eating with the fasting mimicking diet has helped my many menopausal patients maintain their health and vibrancy. When women can control their menopausal symptoms, lose weight, in addition to physical wellness, they gain optimism. Helping women lead optimally healthy lives after the onset of menopause requires accessing all the therapeutic tools we have. Happily, fasting can be incorporated into that toolbox to support a healthy longevity for the vast majority of our menopausal patients.
AUTHOR BIOGRAPHY:
1. Bernhardt et al. 2019. The Lancet; 4 (11) PE539-E540. 2. Ossewaarde et al. 2005. Epidemiology; 16. 556-62. 3. Choi et al. 2017. J Microbiol Biotechnol; 27(12): 2228-2236. 4. Naftolin et al. 2019. F1000Research; 8, 1576. 5. Hatcher et al. 2020. Eur J Neurosci; 51(1):217-228. 6. Alirezaei et al. 2011. Europ J of Neuroscience; 33(2): 197-204. 7. Bianchi et al. 2015. Impact Journals; Oncotarget; 6(14): 11806-11819. 8. Wei, et al. 2017. Sci Transl Med. 9(377). 9. Hamid R Farshchi, et al. 2005. The American Journal of Clinical Nutrition, Volume 81, Issue 2, February 2005, Pages 388–396 10. Corey, et al. Nutrients 2019, 11, 2442; doi:10.3390/nu11102442 11. Natali, et al 2017 Volume 77, pp. 199-215
Felice Gersh, M.D. holds dual board certifications in OB-GYN and Integrative Medicine. She is the founder and director of the Integrative Medical Group of Irvine. Follow her on Instagram Dr Gersh is an L-Nutra advisor. @dr.felicegersh. Contact info: fgersh@integrativemgi.com (949) 753-7475
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Gut Hyperpermeability and Autoimmunity By: Julie Beck, DC, MS CSCS The following article is not endorsed and/or supported by The American Academy of Anti-Aging Medicine. The purposes of this publication do not imply endorsement and/or support of any author, company or theme related to this article.
Medicine has a long history of establishing a standard or viewpoint and then being resistant to changing it. The landscape is evolving, however, and a good example is our growing understanding of the mechanisms and drivers of autoimmunity. Equally as dynamic is our understanding of a condition that has now been associated with autoimmunity: leaky gut syndrome or intestinal hyper-permeability.
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Hashimoto’s thyroiditis or Graves’ disease can be diagnosed.
To date, the American Autoimmune
Related Diseases Association (AARDA), a non-profit organization with the mission to raise awareness about autoimmune diseases, estimates that1 more than one hundred different autoimmune
diseases have been identified, with an
additional forty plus illnesses suspected to have an autoimmune component.
Remember, an autoimmune disease occurs when our immune system produces antibodies whose job is to attack what the immune system has tagged as foreign invaders. This is a wonderful survival mechanism when that foreign invader is a pathogen that could harm us. In autoimmune diseases, however, it is our own tissues that are being attacked, leading to dysfunction, deterioration and even destruction of the targeted tissues.
And in case you think that leaky gut
If the antibodies target and attack the thyroid, for example,
in many well-respected gastroenterology
syndrome is only understood by integrative and functional medicine practitioners,
think again. The well-respected researcher Alessio Fasano, MD of Massachusetts
General Hospital in Boston has brought
the concept of intestinal permeability as an initiating driver in the pathogenesis of autoimmune disorders to the
forefront of conventional medicine’s
consciousness with his published research and immunology journals.2
ANTI-AGING MEDICAL NEWS | FALL 2020
Gut Hyperpermeability and Autoimmunity
How does this happen? Our intestinal lining serves many coordinated functions; one less commonly considered is its barrier functions, which provides an interface between the external environment and our internal systemic circulation. With healthy digestion, all food is broken down into smaller particle levels for absorption. Proteins are broken down to the amino acid level, and those amino acids are allowed passage through the intestinal wall, providing building blocks that our bodies require. With leaky gut, the barrier junctions between individual intestinal cells (aka the paracellular space between enterocytes) are no longer “tight,” and proteins slip through these junctions before they are broken down fully into their amino acid components. The body cannot use these proteins, nor can our immune system identify them, so they are tagged as foreign invaders by our immune system, and the body initiates an immune and inflammatory response against them.
Molecular mimicry and autoimmunity Molecular mimicry occurs when our immune system is exposed to specific antigens (those foreign invaders, perceived or real, mentioned earlier) and in genetically susceptible individuals, these antigens cause cross-reactions with structurally similar amino acid patterns found in human tissues.
There are a long list of firmly established associations between specific dietary derived antigens (most commonly from certain proteins in wheat (gluten) and dairy (casein), as well as pathogenic bacteria and the diagnosis of specific autoimmune disorders. The table to the right is an expanded version of the one found on the last page. It includes the associated overgrowth of identified microbe species associated with certain autoimmune disorders where known 3.
The triad of autoimmunity Dr. Fassano wrote an article in the lay magazine Scientific American in 2009 titled “Surprises from Celiac Disease” that I think flipped the scientific conversation of autoimmunity on its head. Dr. Fasano clearly and eloquently described his theory of leaky gut contributing to Celiac disease and autoimmunity to a lay audience; the same research that was initially greeted with skepticism by the research community.4 Dr. Fasano has proposed that for an autoimmune disease to manifest itself, there must be three variables present. He equates these three variables to a three-legged stool or the center of a Venn diagram, where if any of the three are not present the disease cannot manifest.
ANTI-AGING MEDICAL NEWS | FALL 2020
19
Gut Hyperpermeability and Autoimmunity
These three variables are: •
• •
Genetic susceptibility (i.e., an HLA pattern that is particularly efficient at presenting the antigen to the immune system).
If you get food poisoning, zonulin is triggered via the immune system by the bad bacteria you ate, promoting diarrhea An environmental trigger (i.e., antigen). to flush the buggers out. Once the bacteria are gone, zonulin levels lower Intestinal hyper-permeability and the intestinal tight junctions close. (i.e., leaky gut syndrome).
In lectures, Dr. Fasano provides a very descriptive analogy to show how these three variables interact: •
Our genetics are the gun,
•
environmental triggers load the gun,
•
and intestinal hyperpermeability fires the gun.
While it was previously believed that once an autoimmune illness was activated, the process remained ongoing, with remissions and relapses, Dr. Fasano’s research suggests that the process can be modulated and possibly reversed by interrupting one of the modifiable variables of the triad. Dr. Fasano and others suggest that by far the easiest of the three variables to alter clinically is the third: intestinal permeability.
Where gluten fits into all this: Zonulin, discovered by Dr. Fasano and his team in 2000, is a protein that modulates the permeability of the (tight) junctions between the cells lining our digestive
20
tract. Zonulin could be considered a leakiness regulator and a biological door to inflammation and autoimmunity.
It turns out that gluten, or any one of its 50 epitopes, is a strong trigger of zonulin in some populations. No human can completely digest gluten. And for a select population that is sensitive, undigested gluten can trigger the release of zonulin. Increased zonulin levels equate to increased intestinal permeability. 5, 6
“Once gluten is removed from the diet, serum zonulin levels decrease, the intestine resumes its baseline barrier function, the autoantibody titers are normalized, the autoimmune process shuts off and, consequently, the intestinal damage heals completely.”5
Other variables that can increase zonulin and promote leaky gut include: •
Parasitic infections
•
Bacterial or fungal dysbiosis
•
SIBO = small intestinal bacterial overgrowth
ANTI-AGING MEDICAL NEWS | FALL 2020
Gut Hyperpermeability and Autoimmunity
Effective supplemental agents commonly used to address intestinal permeability •
L-glutamine
•
N-Acetyl-glucosamine
•
Mucilaginous herbs (fenugreek, licorice, marshmallow root, slippery elm)
•
Direct acting anti-inflammatory botanicals (boswellia serrata, zingiber officinale, uncaria tomentosa, salix sp.)
•
REPAIR with supplements listed above
•
REBALANCE with probiotics
Summary It is hoped that this article has provided a comprehensive framework for your understanding and approach to addressing autoimmune disorders and their relationship to intestinal hyper-permeability.
•
Indirect-acting anti-inflammatory botanicals (oregano, berberine, artemisia)
In such complex dysregulated physiological conditions, a systematic approach to treatment with time for the body to heal and adjust is required.
•
Quercetin
As discussed, remember to:
•
Zinc-carnosine
•
Omega-3 fatty acids
•
Vitamin D
•
Digestive enzymes
The FOUR-Step Plan for gut health •
•
REMOVE foods, stress, lack of sleep and other factors that damage the gut
•
Detect and eliminate food sensitivities
•
Focus on optimizing GI mucosal immune function and the microbiome (use the Four-Step Food Plan as a basic framework)
•
Identify and eradicate infectious and parasitic triggers with antimicrobial therapy
•
Promote an antiinflammatory lifestyle
REPLACE digestive enzymes and healing foods (bone broth, fermented foods, coconut products (MCFA), etc.)
ANTI-AGING MEDICAL NEWS | FALL 2020
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Gut Hyperpermeability and Autoimmunity
REFERENCES 1. http://www.aarda.org/autoimmune-information/list-of-diseases/ 2. Fasano A and Shea-Donohue T, “Mechanisms of Disease: The Role of Intestinal Barrier Function in the Pathogenesis of Gastrointestinal Autoimmune Diseases,” Nature Clinical Practice Gastroenterology & Hepatology, Vol. 2, No. 9, 2005, pp. 416-422. 3. Mayes MD, “Epidemiologic Studies of Environmental Agents and Systemic Autoimmune Diseases,” Environmental Health Perspectives, Vol. 107, Supplement 5, 1999, pp. 743-748. 4. Fasano A, “Surprises from Celiac Disease,” Scientific American, Vol. 301, No. 2, 2009, pp. 54-61. 5. Vojdani A, “For the Assessment of Intestinal Permeability, Size Matters,” Alternative Therapies in Health and Medicine, Jan/Feb 3013, Vol 19. No.1
AUTHOR BIO
Julie Beck, DC, MS, CSCS, holds a doctorate in chiropractic and a masters in nutrition. Beck is a former medical educator for Emerson Ecologics and maintains a part-time functional medicine, chiropractic, and physical therapy practice.
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ANTI-AGING MEDICAL NEWS | FALL 2020
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DIM from Cruciferous Vegetables for Men’s Health By: Whitney Crouch, RDN, CLT The following article is not endorsed and/or supported by The American Academy of Anti-Aging Medicine. The purposes of this publication do not imply endorsement and/or support of any author, company or theme related to this article.
Cruciferous vegetables belong to the Brassica genus of plants and include foods such as broccoli, arugula, Brussels sprouts, mustard and collard greens, cabbage, and watercress. Known for their cancer-fighting biological properties and support of the body’s natural detoxification system, these veggies contain sulfur-containing chemicals called glucosinolates, which are responsible for the vegetable’s pungent aroma and bitter flavor.1 During the digestion of cruciferous vegetables, glucosinolates are broken down to form biologically active compounds such as indoles, nitriles, thiocyanates, and isothiocyanates.2 One of these compounds, indole-3carbinol (I3C), is then converted into 3,3’-diindolylmethane (DIM) in the stomach; both compounds are known for their health supportive characteristics.3 24
Studies investigating these unique nutritional bioactives, I3C and DIM, have found that I3C is unstable in the acidic stomach acid environment and is rapidly converted to DIM.4 To simplify the discussion, some of the observed effects of I3C will be assumed for DIM, except for any dose-specific references.4-6 I3C and DIM are best known for their use in cancer prevention applications and female hormone balance, with DIM regarded as a go-to support for reducing excess estrogens in the body.78 While it’s predominantly regarded as a women’s health ingredient, DIM is not a compound just for women.
DIM FOR MEN Prostate Cancer Prostate cancer is the most common nonskin cancer in American men, with a lifetime
ANTI-AGING MEDICAL NEWS | FALL 2020
DIM from Cruciferous Vegetables for Men’s Health
risk for diagnosis of approximately 15.9%.9 It is estimated that 164,690 new cases were diagnosed, and 29,430 patients died from prostate cancer in 2018.9 Nutrition represents a modifiable cancer risk factor that practitioners can and should leverage in their patients. Epidemiological evidence demonstrates that consumption of cruciferous foods has been associated with decreased prostate cancer incidence10 and risk.11 So, how much broccoli, you ask? Consuming ≥ 3 servings of cruciferous vegetables (as compared to < 1 serving/ week) was associated with a 41% risk reduction in prostate cancer.11
mg/kg) and chloroquine (60 mg/kg), taken 3x/week, significantly decreased prostate cancer (PC-3) tumor growth in vivo after 3 and 4 weeks of treatment.10 The mouse prostate cancer model used was a unique one, as the researchers performed a xenograft (i.e., tissue graft from a donor of a different species from the recipient) of human prostate cancer cells A more active type of DIM, 4,4’-Br2DIM, given at the same dose (10 mg/kg, 3x/week) was found to significantly inhibit tumor growth after 4 weeks of treatment, making DIM a novel addition to prostate health plans and prostate cancer treatments.10 Translation: DIM paired with chloroquine for 3 to 4 weeks can slow prostate tumor progression.
Crucifer bioactives I3C and DIM have been studied for their anticancer pathophysiological properties. Mechanistically, it is thought that the antiprostate cancer effects of I3C and DIM are driven by DIM’s inhibitory effects on androgen-mediated pathways, meaning multiple testosterone-producing pathways are reduced through different mechanisms of DIM’s bioactivity.8 Furthermore, DIM imparts anti-cancer effects via its ability to reduce cell proliferation, provoke cell cycle arrest, induce cell death (apoptosis) and autophagy in human prostate cancer cells.12-13
Next, a clinical study used a nutritional grade, absorption-enhanced DIM (BR-DIM) given in 225 mg doses 2x/ day for a minimum of 14 days in 41 Caucasian (55%) and African American (40%) patients with localized prostate cancer.13 Baseline plasma DIM blood levels were assessed in patients, who were given BR-DIM for 14-72 days before undergoing a radical prostatectomy; blood DIM levels were re-tested immediately prior to surgery and during a followup to surgery within 24 months postoperation. Prostate tissue DIM was also measured at the time of surgery.
A preclinical study in a mouse model found that a combination of DIM (10
Biologically significant levels of DIM concentrations were found in
ANTI-AGING MEDICAL NEWS | FALL 2020
25
DIM from Cruciferous Vegetables for Men’s Health
prostate tissue by day 14 of BR-DIM supplementation, with no incremental increases achieved with BR-DIM treatment of longer duration.13 Further, a reduction in PSA levels was observed in the majority (71%) of study participants.13 Lastly, BRDIM had a significant, anti-androgenic impact on the nuclear translocation of the androgen receptor (i.e., exclusion from the nucleus) in 96% of patients; this receptor plays a key role in prostate tumor pathogenesis via testosterone binding.13 Translation: BR-DIM treatment produced clinically relevant DIM levels in the prostate and reduced the effectiveness of androgen receptors to bind testosterone, which has potential chemopreventive implications for prostate cancer. Finally, a double-blind, randomized, placebo-controlled clinical trial examined the efficacy of a pharmaceutical DIMcontaining drug (900 mg/day DIM) in 21 patients with high-grade prostatic intraepithelial neoplasia (PIN), a major risk factor for development of prostate cancer.14 An interim analysis of data after 12 months of treatment demonstrated a significant reduction in the morphological index (based on histological examination of prostate biopsy specimens) in the treatment group as compared to placebo.14 Additional treatment group effects include an improvement in maximal urinary flow rate and a complete regression of PIN in 45% of patients. Translation: intermediate results from a DIM drug trial demonstrate significant clinical promise for patients with high-grade PIN. Other male-centric hormonal applications 26
In addition to its aforementioned role in hormone-related prostate cancer, DIM may support other areas of men’s health. Obesity A preclinical study in mice compared the effects of a high-fat diet (HFD) vs. control diet within the context of DIM supplementation.15 In the mice fed the HFD, 50 mg DIM per kg body weight suppressed HFD-induced obesity; the group receiving the HFD alone gained weight and fat tissue, while the group receiving the HFD plus DIM did not gain weight nor adipose tissue, likening them to the control diet group.15 Furthermore, cellular analyses revealed that DIM significantly inhibited adipogenesis of pre-adipocyte cells.15 In other words, DIM has anti-obesity properties. Estrogen-Related Effects More often discussed in women’s health conversations, one well-known characteristic of DIM is its ability to reduce excess estrogen in the body and convert the more carcinogenic type of estrogens (16-hydroxy and 16-methoxy estrogens) into the “good estrogens” (2-hydroxy and 2-methoxy estrogens).16 But, men make estrogens too through the conversion of testosterone into estradiol via the aromatase enzyme. By DIM reducing excess estrogens in men (possibly caused by genetics, diet, or xenoestrogen exposure), there may also be a reduction in estrogen-excess symptoms like fatigue, erectile dysfunction, obesity, and estrogen-related cancers.15-16
ANTI-AGING MEDICAL NEWS | FALL 2020
DIM from Cruciferous Vegetables for Men’s Health
Clinical Takeaways: •
DIM is not just an indole phytochemical that supports women’s health, but men’s health as well
•
DIM may be used as a preventative measure in men with certain risk factors for prostate cancer (e.g., PIN), and as an adjunct therapy during conventional treatment for certain types of prostate cancers
•
DIM may support healthy testosterone-to-estrogen balance
in males, which in turn can improve myriad symptoms and clinical manifestations of estrogen excess If you suspect estrogen excess or would like to learn more about DIM’s appropriateness for a specific prostate condition, consult with a qualified healthcare provider for hormone testing and personalized clinical recommendations.
CITATIONS 1. NIH. Cruciferous vegetables and cancer prevention. https://www.cancer.gov/ about-cancer/causes-prevention/risk/diet/cruciferous-vegetables-fact-sheet. Accessed December 18, 2018. 2. Hayes JD et al. The cancer chemopreventive actions of phytochemicals derived from glucosinolates. Eur J Nutr. 2008;47 Suppl 2:73-88. 3. Li Y et al. Recent progress on nutraceutical research in prostate cancer. Cancer Metastasis Rev. 2014;33(2-3):629-640. 4. Anderton MJ et al. Pharmacokinetics and tissue disposition of indole-3carbinol and its acid condensation products after oral administration to mice. Clin Cancer Res. 2004;10:5233–5241. 5. Weng JR et al. Indole-3-carbinol as a chemopreventive and anti-cancer agent. Cancer Lett. 2008;262:153–163. 6. Grose KR et al. Oligomerization of indole-3-carbinol in aqueous acid. Chem Res Toxicol. 1992;5:188–193. 7. Murillo G et al. Cruciferous vegetables and cancer prevention. Nutr Cancer. 2001;41(1-2):17-28. 8. Wang TT et al. Broccoli-derived phytochemicals indole-3-carbinol and 3,3’-diindolylmethane exerts concentration-dependent pleiotropic effects on prostate cancer cells: comparison with other cancer preventive phytochemicals. Mol Carcinog. 2012;51(3):244-256.
epidemiological evidence. Nutr Cancer. 2002;42(1):1-9. 11. Cohen JH et al. Fruit and vegetable intakes and prostate cancer risk. J Natl Cancer Inst. 2000;92(1):61-68. 12. Draz H et al. Autophagy inhibition improves the chemotherapeutic efficacy of cruciferous vegetable-derived diindolylmethane in a murine prostate cancer xenograft model. Invest New Drugs. 2018;36(4):718-725. 13. Hwang C et al. Anti-androgenic activity of absorption-enhanced 3, 3’-diindolylmethane in prostatectomy patients. Am J Transl Res. 2016;8(1):166-176. 14. Paltsev M et al. First results of the double-blind randomized placebocontrolled multicenter clinical trial of DIM-based therapy designed as personalized approach to reverse prostatic intraepithelial neoplasia (PIN). EPMA J. 2016;7:5. 15. Yang H et al. 3,3’-Diindolylmethane suppresses high-fat diet-induced obesity through inhibiting adipogenesis of pre-adipocytes by targeting USP2 activity. Mol Nutr Food Res. 2017;61(10). 16. Wendlová J. Scientific medicine in integrative treatment of erectile dysfunction. J Integr Nephrol Androl. 2015;2:5-18 17. Wu F et al. Levels of estradiol and testosterone are altered in Chinese men with sexual dysfunction. Andrology. 2016;4(5):932-938.
9. Siegel RL et al. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7–30. 10. Kristal AR et al. Brassica vegetables and prostate cancer risk: a review of the
WHITNEY CROUCH, RDN, CLT
Whitney Crouch is a Registered Dietitian who received her undergraduate degree in Clinical Nutrition from the University of California, Davis. She has over 10 years of experience across multiple areas of dietetics, specializing in integrative and functional nutrition and food sensitivities. When she’s not writing about nutrition or educating others, she’s spending time with her husband and young son. She’s often found running around the bay near her home with the family’s dog or in the kitchen cooking up new ideas to help her picky eater expand his palate.
ANTI-AGING MEDICAL NEWS | FALL 2020
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A Comprehensive Range of Practitioner-Grade Formulas to Support Hormone Health Hormones are involved in most basic processes within the body for both men and women. Hormones play a role in a variety of general and sex-specific functions, including mood, sexual libido, premenstrual syndrome (PMS), weight management, and energy levels. Metagenics builds upon this science to offer an extensive line of nutritional formulas that target specific support areas for men’s and women’s hormonal health.* • Axis Endo™ Specialized support for hormone metabolism in men and women* • EstroFactors® Features phytonutrients and BioResponse DIM® • Meta I 3 C® Designed to promote healthy estrogen metabolism and balance* • Testralin® Testosterone balance support*
Contact your Metagenics representative today to learn more, or visit Metagenics.com
*These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease. © 2018 Metagenics, Inc. All Rights Reserved.
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