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  • December 05, 2015 9:19 AM | Christiaan Killian (Administrator)
    NEAL ROUZIER, M.D.

    Introduction to Preventive Medicine

    If you want to think, feel, act, respond, perform, heal, exercise, and function the way you used to, then hormone replacement (HRT) is your answer. If you want to improve your skin, aesthetics (maintain muscle and burn fat), and look the way you used to, then HRT is your only option. If you want to regain strength, energy, endurance, and recovery, then HRT is you only hope. If you want to improve health, wellness, longevity, quality of life, then HRT is a must. If you want to improve libido, sexual response, erectile function, and orgasmic ability for both you and your spouse, then you both need to be on hormones. If you want to live a longer, happier, healthier life with less morbidity (increased health span), then HRT is for you. If you want to offer these same quality of life benefits for your patients, then you need to incorporate this into your practice. If you want to get it back again, then you must optimize all of your hormones. Sound far-fetched? Not according to the medical literature. There is tremendous scientific support in our medical literature demonstrating the benefits of hormone optimization which is termed anti-aging, age management medicine, or simply preventive medicine. This medical information is in so much demand by the public,  yet it is ignored by physicians.

    This presentation reviews the importance of HRT. What it is, what it isn't, and what it does from a scientific standpoint. Peer reviewed medical research is extensively reviewed to demonstrate all that is known in our literature, yet not embraced or utilized by most physicians and medical academies. This new trend in medicine will be reviewed and analyzed as to the validity of the claims and to enable you to understand the importance of this therapy for both you and your patients. There is no better compliment to your practice. Dr. Rouzier will explain how the practice of age management medicine has changed his practice of medicine, his life, the lives of his patients, and the lives and medical practice for so many of past course attendees.

    Objectives:

    1) Review the new trend in medicine of optimal hormone replacement therapy.

    2) Review the co-morbidities associated with low hormone levels.

    3) Discuss the scientific basis behind optimal hormone replacement = life extension = anti-aging = preventive medicine = age management medicine.

    4) Discuss the patient and consumer demands as well as awareness as to how any physician can incorporate age management medicine into their medical practice.

    5) Evaluate medical studies as they pertain to optimizing thyroid, estrogen, progesterone, DHEA, and testosterone and the resultant effects on health, wellness, debility, obesity and longevity.

    6) Interpret labs, establish protocols and manage cases.

    7) "Monday morning ready" to start treating your patients.


  • August 21, 2015 9:10 AM | Christiaan Killian (Administrator)



    Neal Rouzier's Interesting Case Studies


    These interesting and informative Case Studies were pulled and submitted by Neal Rouzier.

    Questions will by typed out and just hover over the "answer" text to see what Neal has to say.

    Doctor I’m bleeding!

    A 45 year old pre-menopausal woman presents with prolonged periods and heavy bleeding. Ultrasound shows no fibroids or polyps. Endometrial stripe is normal and endometrial biopsy is negative. Any endometrial pathology has therefore been excluded. What is the treatment to diminish bleeding acutely?

    1) BCP's  2) Progesterone in high doses  3) Mirena  4) IUD  5) Tranexamic acid (Lysteda)  6) Uterine (endometrial) ablation

    answer

    Question: Amenorrhea vs. Anovulation

    Your 21 year old daughter, a track star, has had no period for 2 years. No symptoms, hot flashes or night sweats or hormonal complaints. Recent OB-GYN tested DEXA and found T-score of -2.4. PMD gave her BCP’s to protect her bones. She doesn’t wish to take and refuses BCP’s. How would you treat your daughter? If it was you, how would you treat yourself?

    answer

    Question: An 80 year old female presents with history of vaginal bleed and endometrial proliferation.  The endometrial stripe measures 0.9 cm: biopsy is negative.  Patient can’t stop estrogen due to vasomotor symptoms and osteoporosis.  She did not tolerate Provera 5mg by PMD.  What is the treatment plan?

    answer

    Question: A 52 year old female presents with severe hot flashes. Her FSH = 56 and her estradiol = 210.  What is the treatment plan?

    answer

    Question: A 44 year old female on BCP’s for PCOS, present with PMS, fatigue, headaches and no libido.  Her total testosterone = 90 (high) and her free testosterone = 0.2 (low).  What is the treatment plan?

    answer

    Have other interesting cases, feel free to send them along.  Hope this is helpful and hope to see you soon at another Worldlink event.

    Sincerely,

    – Neal Rouzier, MD


  • February 25, 2015 9:12 AM | Christiaan Killian (Administrator)

     

    Dear Colleague,

    I am writing to bring to your attention a critically important matter affecting all of us in medicine. The evidence is undeniable: 75% of the maladies that cause our patients to consult with us are preventable or remediable through lifestyle & behavior changes. Moreover, the leading causes of death in the U.S. are largely preventable, for the same reasons. Tragically, sickcare medicine has itself become the 3rd leading cause of death, and at a staggering cost.

    Yet, randomized studies correlate physicians engaged in patient-centered care with fewer hospitalizations, fewer diagnostic tests and specialty referrals, and lower overall medical costs, while several studies document higher utilization rates for diagnostic tests, hospitalizations, prescriptions, and referrals among doctors who are poor communicators. Furthermore, treatment by empathic and communicative physicians has been correlated with improved clinical outcomes such as better control of diabetes. No new expensive oral antiglycemics or new sophisticated monitoring devices are required for this improvement; rather, it appears that when given a better relationship with their care givers, patients respond with better compliance, and, hence, better diabetes control.

    This evidence has not gone unnoticed, as the Institutes of Medicine, CMS and CG-CAHPS are reporting patients’ ratings of our compassion, empathy, communication skills and even patient experiences, as critical elements of quality. The question is, are you fully prepared?

    The New Art of Medicine Workshop is timely in that it prepares you to thrive in a healthcare system with an increasingly patient-centric focus, one that financially rewards practitioners based on the patient’s experience, the provider’s empathy & communication, and improved patient outcomes. This workshop will expand your attention from “What’s the matter” with your patient to include “What matters” to your patient. You will improve your competitive position, gain financial incentives with payer reimbursement, and grow a loyal patient base. If you are a practice leader who is not content to just wait and see what happens next, the New Art of Medicine Workshop is for you.

    Sincerely,

    Gregory W. Petersburg, D.O.


  • November 13, 2014 9:20 AM | Christiaan Killian (Administrator)
    NEAL ROUZIER, M.D.

    Press Release: Neal Rouzier M.D. wins Prestigious Alan P. Mintz Award in Age Management Medicine

    Winners exemplify clinical excellence in age management medicine and represent superior patient care, healthy living, better quality of life and entrepreneurship. 

    Salt Lake City, Utah – November 10, 2014 - Worldlink Medical is pleased to announce their lead instructor Neal Rouzier, M.D. as the recipient of the 2014 Alan P. Mintz, MD award.  Dr. Rouzier is the author of How to Achieve Healthy Aging: Why everyone should replace hormones, a review of the medical literature.  He is passionate about helping patients live a healthier life.

    This award named in remembrance of Alan P. Mintz, MD, a mentor, innovator and visionary in Age Management Medicine that inspired many with his brilliant insight and desire to help others live a vital life.  He forged new medical frontiers and embraced the spirit of determination and medical excellence.Dr. Rouzier is the eighth recipient of this award which follows his 2013 Worldlink Medical Lifetime Achievement Award for 20 years of dedication as an educator in the field of evidence based medicine.

    His clinical excellence, exemplified by his teaching style  is unique in ensuring clinical competency that includes extensive literature review combined with diagnosing, prescribing, monitoring and adjusting based on symptoms and lab tests.  Case management through case presentations helps solidify concepts learned and ensures a high level of training and competency for those attending.  His Four Part Training Series and Certification program is highly respected and sought after.

    Dana Burnett, Managing Director of Worldlink Medical “is not surprised he won this award.  His teaching style and evidence based approach has revolutionized the efficacy with how practitioners practice bio identical hormone replacement therapy.  Dr. Rouzier is a pioneer in the field and we are grateful for his ongoing contribution in preventive care and wellness.”

    Worldlink Medical is a non-profit academy for continuing Medical Education (CME) for healthcare practitioners.  Our mission links the science of medicine, the art of caring and the experience of learning to transform individuals, communities and the world.  Educational initiatives focus on upstream medicine and prevention as opposed to downstream sick-care medicine that relies on medication to treat symptoms but not the underlying causes of disease.  Estimates report that 60% of our population suffers from one or more chronic diseases; it is imperative that the private sector step up and support those suffering from disease and begin teaching their patients healthier lifestyle behaviors.  Worldlink Medical with the help of Dr. Rouzier is a leader in evidenced based training in helping practitioners optimize hormones for their patients.

     

  • July 24, 2014 9:24 AM | Christiaan Killian (Administrator)

    After a recent article on testosterone use was published in the Journal of the American Medical Association (JAMA), there has been an opportunity for law firms to capitalize on the suggested correlation between testosterone use and increased heart attack risk. However, the observational study behind the article suggesting such correlation has received significant criticism on the basis of flawed study designs and serious analysis errors. Dr. Neal Rouzier, BHRT pioneer and expert, has written a critical review of the study’s resulting article from JAMA and television advertisements for various law firms.

    Download the Article


  • March 14, 2014 9:27 AM | Christiaan Killian (Administrator)

    The information contained on this blog is for educational purposes only. Titles and institutional affiliation for individuals who contribute to this blog are for identification purposes only. The opinions expressed are solely those of the blog post author and do not represent the views of any organization that the post author is affiliated with or with the opinions of any other author who publishes on this blog.

    NEAL ROUZIER, M.D.

    It was bound to happen sooner or later. I recently saw an ad on television soliciting patients by a law firm. “If you have been taking testosterone and recently suffered a heart attack, then you may be entitled to a large compensation from the pharmaceutical company that caused your heart attack. A recent study showed that testosterone therapy can cause heart attacks. Contact the experts in pharmaceutical claims to get you the compensation that you deserve.” Perfect!

    Oddly enough only a few of my patients have contacted me out of the large population of men that I treat with testosterone, and I have heard from no one that stopped their testosterone. Patients seem to somehow understand that the recent media hype is just that, hype. On the other hand I have received emails (again) from several hundred physicians asking my take on the latest study and what advice I have for them. My advice is the same that I gave in November for the last negative article on testosterone: one (or two) negative observational studies of questionable power do not negate many other prior RCT’s that show benefit and lack of harm. Over 50 years of well designed controlled trials, as well as laboratory research, should not be ignored based on several observational studies of questionable design. All be it, clinical decision making should be the summation of all available data and not reflexive rejection of all past studies based on one recent observation. Had this study, or review, occurred 40 years ago it probably would be very much ignored today due to the succeeding 40 years of data after the study that supports safety and efficacy of testosterone administration. However since it is of recent publication, it catches the public eye as well as all the naysayer physicians (and legal zealots) that will jump on the bandwagon to condemn all the physicians (and patients) that take or prescribe testosterone. (Sounds just like the WHI all over again). The true challenge that we will face is to convince our peers that an MI that occurs in a man that has been on testosterone for years is probably not due to testosterone but rather the natural course of the disease. Nevertheless, there have now been several recent negative reviews (I have difficulty referring to them as studies) that should be addressed and not completely ignored. Forty years of positive studies of women’s hormones were suddenly challenged by the WHI and HERS trials that proved undiscovered harm of cardiac events in some older women (30 per 10,000) with pre-established heart disease. These recent reviews certainly require careful scrutiny but also concern if there is truly an early iatrogenic, thrombotic effect of testosterone that to date has not been evident. I therefore do not change my therapy based on several studies of weak data that is the opposite of the plethora of data showing safety and benefit. Rather, I base my therapy on a composite of many studies over several decades of research. As stated recently in Family Practice News, February 15, 2014: “The FDA has not concluded that approved testosterone formulations increase cardiovascular risk. Final recommendations are pending.” Hopefully the FDA will access all prior studies in addition to the recent study before coming to any conclusion.

    A Review of the Recent Study

    The gist of the PLOS study was that researchers encountered an unexpected increased incidence of MI shortly after initiating testosterone therapy. The risk was seen in older men, both with and without a prior history of heart disease, and in younger men with prior CVD. This same phenomenon was also observed in older women that started HRT in both the HERS and WHI trials, whereas we had 40 years of prior study demonstrating a protective effect of estrogen on CVD. Is there a pro-thrombotic effect of testosterone in men similar to the pro-thrombotic effect of menopausal hormones in older women many years out from menopause? Several recent studies seem to suggest this and therefore this phenomenon should not be ignored. There was also a similar pro-thrombotic effect in younger men with pre-existing CVD, whereas there was no pro-thrombotic effect seen in younger men who were healthy. This begs the question as to whether there is a pro-thrombotic effect of testosterone on diseased arteries similar to the pro-thrombotic effect that estrogen has on diseased vessels in women that start estrogen for the first time and are beyond the 10 year protective window since menopause as seen in the WHI. Oddly enough, and similar to that seen in the WHI study, after 3 months of TT the incidence of MI seemed to resolve once the men (and women) with the diseased vessels get weeded out. We then experience a protective effect on the vasculature due to the many positive effects demonstrated on lipids, lipoproteins, inflammatory cytokines, endothelium, visceral fat, and BMI. So far this phenomenon in men seems to be identical to that in women in the HERS and WHI trials with older men (and women) suffering an MI (plaque rupture) after initiation of HRT. However now we see an early and unexpected inflammatory effect seen in men with significant pre-existing disease that occurred late in the course of their vascular disease process causing rupture in plaque, destabilization and thrombosis. This effect in men, similar to women, shows that heart disease ≠ heart disease. One type of heart disease is slow deposition of plaque over years (protection against which has been clearly demonstrated for both estrogen and testosterone in multiple studies). A completely different type of heart disease that involves plaque rupture occurs only in mature plaque with a necrotic core that ruptures due to some inflammatory factor (as in matrix metalloproteinase or MMP-9) and occurs in older women with pre-established severely diseased vessels. As in the HERS and WHI, younger women that did not have diseased vessels did not suffer plaque destabilization and rupture as did older women, and these women derived CVD protection by prevention of plaque build-up. In other words, it requires healthy vessels to achieve benefit (prevention of plaque build-up) whereas diseased vessels may thrombose secondary to some undiscovered inflammatory effect similar to that caused by increased MMP from first pass effect of oral estrogen that ruptures plaque in severely diseased coronary arteries. If this truly is the same process, let us not repeat history and ignore these observed pro-thrombotic effects of HRT which can lead to an increase in CAD (plaque rupture but not plaque deposition) and CVD in women, just as we observed in the WHI and HERS trials. As we learned from the WHI, early administration of estrogen is protective and should be started early, long before some vessel becomes seriously diseased. On the other hand we really need to further investigate any possible thrombotic effect on diseased vessels so that we can avoid an increase in MI, just as we witnessed in the WHI and HERS studies. In women, avoiding first pass effect of oral estrogen by using transdermal estrogen eliminated that plaque rupture from oral estrogen as there is not any pro-thrombotic effect from transdermal estrogen as it does not raise MMP.

    I have read many different posts from physicians, all criticizing the study design and rejecting the outcomes. In fact I don’t think that I have read one physician rebuttal that did not reject the design and/or findings of this study. And I agree that we should not extrapolate a poorly designed and weak study to include all men on testosterone, i.e. don’t repeat the WHI fiasco. However, rather than rejecting and ignoring this study for its flaws, perhaps we should carefully reconsider our denigration of this study, and other recent studies, so that we don’t make the same mistakes that we did by rejecting the WHI and HERS analysis. As of right now, my take on this study is that there truly might be an early pro-thrombotic effect from testosterone administration as evidenced by 3 most recent studies demonstrating such risk. There is a pattern here that should not be ignored, yet should be further studied and evaluated. This would then allow us to be most cautious in our prescribing to older men with pre-established CVD so that we don’t cause any increase in morbidity or mortality. On the other hand, we should still continue to prescribe testosterone to all younger men (and healthy older men) just as we have been doing in order to prevent the plaque from forming in the first place. Prevention of ASVD thereby would prevent any future plaque rupture as there would not be any plaque present to rupture. However, once an older man develops this unstable vulnerable plaque, it could rupture upon starting testosterone for the first time. I will still continue to do what I have been doing by prescribing testosterone to most men, but I might be more cautious in prescribing testosterone for the first time to older men that have pre-existing disease or significant risk factors for such. In women the solution is simple by avoiding oral HRT that can cause plaque rupture through first pass effect that increases MMP that is responsible for the plaque rupture. Transdermal estrogen is the simple solution/prevention in older women that have diseased vessels as later studies demonstrate excellent safety of transdermal estrogen. Therefore we avoid oral estrogen in any women that may be at risk. The answer, however, is not as easy in men as we don’t know/understand the mechanism that is responsible for the plaque rupture and I’m not sure what the solution will be. However, according to the most recent study, if you believe it, there is no risk in younger men and TRT may certainly be of benefit, according to the last 50 years of studies. And the apparent risk was seen only in the first 90 days which should provide confidence in continuing TT in current users. We should use our medical literature to guide our therapy and learn to decipher and analyze these studies, keeping in mind that one or two studies do not negate 4 decades of study and our course of therapy should be based on the summation of all the data and studies, not on just one or two contradictory studies to dictate our therapy. Years of studies prove the effect of testosterone in preventing plaque deposition which should be our goal. Preventing the plaque from forming in the first place would thereby render any future pro-thrombotic effect of testosterone improbable. However lack of that beneficial effect of testosterone in protecting the vasculature, i.e. not utilizing testosterone for its anti-atherogenic effect, may eventually lead to this pro-thrombotic effect on already established mature plaque as seen in older women in the HERS and WHI trials. Knowledge of all the studies on women’s hormones, as presented in Parts III & IV of the WorldLink Medical courses, is tantamount to understanding the mechanism by which testosterone may do the same.

    In addition to the PLOS study which demonstrated harm in the first 90 days of initiation of therapy, which is the most recent published and criticized study, there was also a recent separate retrospective analysis of 8,000 men that also showed an increase in MI and CVA within the first year of therapy. In contrast to the PLOS study, this study is more similar to the WHI and HERS trials that demonstrated harm within the first year of initiating therapy. This early pro-thrombotic effect of testosterone then diminishes with time, resulting in less relative risk as time progresses which can also provide security to practitioners in not needing to terminate long-term administration. Again, as per recent FDA recommendations, men should continue their current course of treatment until final analysis is made by the FDA.

    What My Study Indicates

    Some others have posted criticism as to the type of study (pick and choose from a data bank without any control or randomization). Picking from a data bank sure can be fraught with error, slanted, and biased which detracts from the credibility of the study as opposed to having a randomized, controlled trial. Others have presented excellent rebuttals and criticisms. I have a very geriatric practice in Palm Springs and have an excellent patient population that provides a similar age range as did the article by Finkle et. al. In my population of older men that I have placed on testosterone, I have not encountered one patient that developed an MI while on testosterone or upon initiating it in over 15 years. It is true that some have moved or been lost in follow up, however during this time of initiation the patients are seen on a monthly basis and not one patient reported to us on follow up that an MI occurred. I had taken over a practice of 5,000 established patients. Out of this population, I have treated approximately 2,000 men and with an average age of 60-70 (that certainly would have included by chance many men with pre-existing heart disease). I feel confident that the population that I have scanned is quite similar to the one published in PLOS. When I took over my current practice, I solicited all male patients with the intent of initiating testosterone for purely preventive medicine reasons and cardiovascular protection, compatible with so much of the literature in the past 15 years. I thought that I was providing an excellent preventive service and treatment that which most physicians were unaware. The current search of my patient population also included new patients that were of varying age groups, some of which included older men similar to the age range of my pre-existing patient population. Just from natural selection, I would have imagined that at least one man would have ruptured plaque and had an MI, yet I did not find that in my records. More importantly, however, not one patient had suffered an MI after initiation of testosterone in my 15 years of treating men. The PLOS study demonstrated that in older men, as well as in younger men with pre-existing CVD, the risk of MI following initiation of TT is substantially increased. In my cohort of approximately 2,000 patients, which I feel is an excellent older cohort of men to search and evaluate, I did not find one patient that experienced an MI, either immediately after initiation of TT or thereafter. My patient population was quite small (2,000) in comparison to the large number (55,000) studied in the PLOS. Nevertheless I did not encounter any adverse event in the last 15 years. Of course my study is not a study, rather it is an anecdotal observation of “my” patient population which I feel is fairly well representative of an older population that might be prone to plaque rupture, but they didn’t! My study shows no increased risk of MI and prolonged safety of therapy. However it is an observation, not a RCT, and that’s all that should be surmised from my study population. Maybe it was the clean desert air that was protective and not the testosterone? Perhaps my caring staff was the protective effect? Regardless of whatever association I might claim, it does not prove that anything that I did, including administering testosterone, resulted in any protection or benefit and any claim by me is only speculation.

    The same critique of my study applies to the PLOS: small sample, subject to selection bias, so on and so forth. Everyone in every post has their own take or criticism of the PLOS article by which they reject the results or conclusions (and extrapolations) of the study. Nevertheless, three recent studies have raised some concerns about possible adverse cardiovascular outcomes from TT, especially myocardial infarction, and we should not ignore this. A meta-analysis of smaller studies also suggests an increase in cardiovascular risk. The recent VA study also reported an excess of events, however an identical study in a similar VA cohort 2 years ago did not. We should keep in mind though that these are observational studies in design, and other recent more powerful controlled trials did not show cardiovascular harm which has supported the long term safety seen in 40 years of study. I cannot emphasize the importance of realizing that one or two negative studies, that are weak studies in contrast to RCT’s, do not negate all of the past 40 years of positive studies that demonstrated the opposite of this study and that are RCT’s with more power and predictive value. A recent statement from the AACE is right on when they suggest that physicians and patients not jump to conclusions and stop the testosterone prescription, rather patients should continue taking testosterone until further evaluation and review by the FDA is complete. The PLOS study creates more questions than answers, but we should not change 40 years of practice and positive studies based on several observational studies. However we should not ignore them either.

    The Issue and Concern of Recent Studies

    The issue and concern with several of the recent studies, though, is the increase in events that appear very soon within 3 months of initiation of TT. This is similar to the harm seen in the first year of initiation of HRT in older women with pre-existing CVD. For decades the medical literature supported a protective effect of estrogen against cardiovascular disease. The medical establishment was shaken when 2 studies (HERS & WHI) demonstrated increased cardiovascular harm in older women with pre-existing disease that was felt to be due to plaque rupture from the enzymatic degradation of the inner necrotic core by MMP production through first pass liver effect that occurred within the first year of initiating HRT. Utilizing transdermal estrogen, and avoiding the first pass effect of oral HRT, has resulted in no further risk (plaque rupture) by HRT in older women that initiate HRT more than 10 years after menopause which is the time frame for them to develop mature vulnerable plaque that can rupture by enzymatic degradation by MMP-9. The current studies on TT have the same pattern of risk enhancement soon after initiation of therapy which is consistent with an effect of the drug on thrombosis. This underscores the concerns of initiating TT in men with pre-established disease as evidenced in these recent studies, and particularly in older men as well as younger men with more extensive coronary vascular disease. On a good note, and similar to the results seen in the HERS and WHI trials, this early pro-thrombotic risk diminishes with time such that after 90 days of therapy the risk decreases and TT (and HRT) become protective. This appears to be same with TT and it makes no sense to stop TT if there is a long-term protective effect once men pass that 3 month window of harm. This bodes well for both patients and practitioners in that once they have been on the therapy for 90 days, any risk subsides and therapy thereafter does not appear to be harmful. As the result, stopping TT does not appear to be indicated in men once they have been on TT for a period of time, and TT is protective once the patient is past that critical window of plaque rupture, and this applies to both men and women.

    On the other hand, a plethora of data and studies supports that low endogenous levels of testosterone may be positively associated with cardiovascular disease. Many RCT’s have demonstrated the protective effect of testosterone replacement, both on symptomatic improvement as well as CVD progression. I refer you to my prior post from November 2013 where I listed many of those trials providing evidence and confidence for those of us that continue to prescribe TT for health and wellness. However I urge caution in prescribing TT to any man with pre-existing CVD or to one that may have the undiagnosed disease with many risk factors. On the other hand it does not make sense to prematurely stop TT once a patient has passed the critical window of plaque rupture which seems to be 90 days, as per the recent studies. Utilize extreme caution when initiating TT and perhaps do further work up and evaluation to discover any undiagnosed CVD and thereby use caution in initiating therapy as well as thoroughly discussing the issues and concerns with the patient. Given the popularity of TT, the current study emphasizes the urgency for further study of this early pro-thrombotic effect and the need for addressing the potential risk of TT in men with pre-existing CVD.

    Lastly, and beyond the scope of this review, I found the comments from the many posts amazing, entertaining, fascinating, and troubling as to the proposed mechanism of harm of testosterone. These will be addressed in a separate post but briefly mentioned here. Similar points/concerns/causes for the increase in risk of CAD were also addressed by the authors of the PLOS study. However, most physicians do not understand the effects of testosterone on erythrocytosis or aromatization into estrogen, both of which are incorrectly claimed to result in thrombosis and clotting. Testosterone does not cause polycythemia, RBC clumping, hyperviscosity, or platelet aggregation as they surmised. Polycythemia (PV or polycythemia vera) does cause the foregoing, however testosterone does not cause polycythemia, rather testosterone produces physiologic erythrocytosis via increase in erythropoietin produced in the kidneys. Unfortunately everyone mistakenly makes claim that testosterone causes PV but it does not. See the this article on polycythemia vera and my article on polycythemia vs. erythrocytosis. If erythrocytosis truly caused thrombosis and “RBC clumping”, then we would witness a later and persistent effect on clotting as erythrocytosis (increase in RBC’s) occurs after several months of therapy and not much during the first three months of therapy which is the time frame of harm in the recent study. Therefore if erythrocytosis were the culprit, then we would continue to see the thrombosis escalate as time progresses but we don’t, either in this study or other long-term studies. The effect on thrombosis should escalate as the erythrocytosis progresses but it doesn’t. More importantly, if erythrocytosis truly caused clotting and RBC clumping, then everyone that lived at altitude (above 5,000 feet) would experience an increase in CAD, CVD, and RBC clumping and clotting. If this did occur, then everyone would run to the beach and not live at altitude. In addition, every patient with COPD with physiologically high RBC counts due to hypoxemia (which I see in the ER daily) would have significant increases in MI and CVA yet we don’t see that either. If we phlebotomized every COPD patient with erythrocytosis, they would all die from hypoxia. Physiologic erythrocytosis is never harmful, only beneficial, otherwise we would phlebotomize everyone that lives at altitude but we don’t. Testosterone causes the same physiologic effect as living at altitude and the effect is only on RBS’s, not platelets. Polycythemia is different and PV is not physiologic erythrocytosis. Polycythemia vera is an increase in multiple (poly) cells including white cells, red cells, and platelets with the resultant splenomegaly, not seen with testosterone use. It is the platelet count of over a million that causes clotting, not high RBC’s. Unfortunately we monitor phlebotomy by hemoglobin counts, and not by platelet counts, which makes us intuitively think that it is the RBC that is the important factor to lower whereas it is the high platelet count that is the culprit and not the high hemoglobin. Just because we monitor RBC counts and adjust phlebotomy based on H & H does not mean or prove that high hemoglobin causes any morbidity or mortality, as does PV. Phlebotomizing lowers platelets and that is the beneficial effect in protecting against thrombosis. The meta-analysis from the NEJM demonstrated that in over 40 years of studies on testosterone therapy, not one study showed any thromboembolic event to date. Polycythemia is a blood cell dyscrasia that causes increased clotting, DVT’s, cancer, myelofibrosis, myelodysplasia, and progression to leukemia. Does any study show that testosterone causes any of this? Absolutely not and therefore testosterone does not cause polycythemia, or an increase in WBC’s or platelets or splenomegaly, in spite of the literature incorrectly stating testosterone causes PV. Multiple published papers mistakenly claim that testosterone causes polycythemia whereas testosterone only causes erythrocytosis and patients should receive the same therapy as those with erythrocytosis that live at altitude-nothing. I recently treated a prominent physician who was overly phlebotomized by a prominent clinic which resulted in extreme fatigue, with a serum iron level of 5 and a ferritin level of 2! IV iron (Venofer) completely resolved the year long fatigue and the physician swore never to phlebotomize again. I’m still searching for that study that demonstrates high H & H with normal platelet count causes harm. Erythrocytosis is not PV and testosterone does not cause PV, regardless of the incorrect claims. My hemoglobin has been above 19 since I was 20 because I have worked and trained at a ski resort since I was 20. My platelet and white counts are normal. I once saw a Sherpa that had a hemoglobin of 23 as he frequently traveled between 20,000 to 30,000 feet. Phlebotomizing patients with PV saves lives as evidenced in the attached article. No study has ever shown benefit to phlebotomizing anyone with physiologic erythrocytosis and normal platelet counts.

    Estrogen in Men

    Last year I presented this lecture at AMMG on estrogen in men. It is commonly accepted that estrogen should be lowered in men due to the cardiovascular complications of high estrogen in men. Nothing could be further from the truth. You may view the lecture at WLM.com. Understanding that observation does not prove causation is paramount to understanding that estrogen does not cause harm in men. Every interventional trial (except for high dose DES) where estrogen has been administered to men has prevented heart disease, both for oral as well as transdermal estradiol. Every long-term study whereby estrogen is elevated through aromatization of testosterone into estrogen has resulted in cardiovascular benefit. Every study where estrogen is blocked or lowered has resulted in harm. Lowering estrogen in men has shown to increase the risk of cardiovascular disease, DM, lipid abnormalities, memory loss, Alzheimer’s disease, bone loss and osteoporosis, and loss of libido and EF. Raising estrogen in men, either via testosterone administration or estrogen administration, has shown protection against the foregoing. I was once tickled by an attendee’s comments that we only want to lower estrogen a little bit. Translation: you only want to increase the risk of CAD, CVD, osteoporosis, DM, and ED a little bit? The estradiol level of a young is 75-90 pg/ml. Should we start blocking estrogen in young men? View the lecture on the harm of using aromatase inhibitors in men.

    The authors of the PLOS study site the same observational studies, as does Life Extension and everyone else, where high estrogen levels in men are associated with increase in CVD. (Remember association does not prove causation). However, it is the increase in visceral fat that increases the production of estrone, and concomitantly estradiol, which only proves an association and not causation. In order to prove causation, one must intervene and administer estrogen. The results of the interventional, randomized trials prove the opposite of the observation that high estrogen is harmful. It is the increase in visceral fat, insulin resistance, inflammatory cytokines, and lipid abnormalities that cause the increase CVD risk, not the claimed estrogen elevation. And how do we then prove that? The answer is simply to intervene and administer estrogen in an interventional trial and observe if the increase in estrogen proves causative or protective. Every study (except the high dose DES) proves a protective effect of raising estrogen, and that applies to both oral and transdermal estrogen. It has been shown that the cardioprotective effects of testosterone are related to aromatization to estrogen. Block the testosterone and the cardioprotective effect of estrogen persists. Raise testosterone and block estrogen and the cardioprotective effect will thereby be eliminated as well as all the beneficial effects on lipids and lipoproteins. Every study whereby estrogen is raised by testosterone administration has resulted in long-term cardiovascular protection. The randomized trials whereby estrogen was administered to men resulted in cardiovascular protection. (View the lecture on line). The randomized trials whereby aromatization is blocked by anastrozole result in loss of CVD protection when estrogen is lowered. So then why is everyone promoting blocking estrogen when studies show harm to lowering estrogen and other studies show benefit when we intervene and raise estrogen? The reason is simply because they don’t understand the literature, the difference between observational vs. randomized trials, or the concept that observation does not prove causation, and the fact that multiple RCT’s prove estrogen’s cardiovascular protective effects, and that observing high baseline levels of estradiol in obese men with heart disease does not prove anything.

    Do Not Extrapolate Effects of Oral Estrogen

    Finally one should not extrapolate the first pass effect of oral estrogen on clotting factors to be the same as raising estrogen via aromatization from testosterone or by transdermal administration. The effect on clotting and clotting factors from oral estrogen is through the first pass liver effect. Transdermal estrogen has never been shown to have the thrombotic effects of oral estrogen, and neither has testosterone. The PLOS authors do make this mistake as testosterone, with the aromatization into estrogen, has never been shown to raise clotting factors, lower clotting inhibitors, or increase clotting as does oral estrogen, yet these authors make claim that raising estrogen via aromatization is the mechanism for the increase in thrombosis. Their extrapolation to testosterone causing the harm of oral estrogen and polycythemia is without any basis in fact.

    Although many articles have many postulated theories as to the cause of this newly discovered plaque rupture in recently treated men, we do not understand the mechanism as of yet. Perhaps some form of testosterone has a similar effect in raising matrix metalloproteinase as seen with oral estrogen thereby causing plaque rupture? Until that research is conclusive, speculation should be careful and cautious. In the interim we must be careful in administering testosterone to older men that may have significant cardiovascular disease. However don’t throw out 40 years of studies that demonstrate long-term cardiovascular protection by testosterone therapy. Treatment should be prevention in the first place by early administration of testosterone and continued indefinitely as per 40 years of study, and then we would never have to worry about that plaque rupture in the first place. Evidence, not conjecture, should guide clinical practice and policies. And don’t extrapolate evidence or conjecture.

    - Neal

    Related Resource:

    The Institute for Continuing Healthcare Education
    A Panel Discussion on the Importance of Early Diagnosis for Myeloproliferative Neoplasms


  • March 11, 2014 9:28 AM | Christiaan Killian (Administrator)

    The information contained on this blog is for educational purposes only. Titles and institutional affiliation for individuals who contribute to this blog are for identification purposes only. The opinions expressed are solely those of the blog post author and do not represent the views of any organization that the post author is affiliated with or with the opinions of any other author who publishes on this blog.

    As the popularity of bioidentical hormones continues to spread, more men and women are finding that balancing hormones improves vitality, health and well-being. But what does the research demonstrate? We’ve hand-selected nine articles with summaries and responses from Dr. Neal Rouzier’s library. The article reviewed in this post comes from the March 2012 issue of The Journal of Clinical Endocrinology and Metabolism.

    Misconception and concerns about bioidentical hormones used for custom-compounded hormone therapy

    (Bhavnani BR, Stancyzk FZ. J Clin Endocrinol Metab. 2012 Mar;97(3):756-759)

    Article Summary: As a review of BHRT dosage, forms, and claims are outlined in this article, the authors explain there is concern that the unregulated BHRT may be overdosed, treated with ineffective products, or contain unknown risks. The authors’ objective was to explain how BHRT may not be identical to hormones naturally produced in the body and that the lack of regulation could cause adverse effects in postmenopausal women.

    Neal Rouzier, MDNEAL ROUZIER, M.D.

    Neal’s Response: I absolutely agree with the conclusions of these authors and that is the main criticism of the bioidentical industry. The main risk that I perceive of compounded BHRT is failure to achieve therapeutic levels of HRT to guarantee therapeutic endpoints. Symptoms may improve for patients on BHRT; however, the doses used and the levels achieved may not provide cardiovascular, musculoskeletal, breast or uterine protection, which defeats the purpose of HRT replacement.

    Most patients that come to me from other BHRT practitioners are taking subtherapeutic amounts. Their prescriptions provide very low serum levels of HRT that will not be protective at all, and that pertains to hormones E2, P4, testosterone, DHEA and thyroid. (The author’s comments about overdosing and unknown risks are over-hyped, as I haven’t seen any overdoses of estriol in the ER lately. If saliva testing shows overdose, it does not correlate with an overdose when testing serum levels, which are more meaningful for hormone therapy.)

    My main criticism of the bioidentical industry is the lack of emphasis to maintaining scientific standards that have demonstrated scientific efficacy of HRT as carried out in the studies. When I prescribe compounded BHRT, I copy and maintain the same standards and levels as seen in the scientific literature that utilizes pharmaceutical BHRT, something that this author probably does not understand. I also have experienced many patients that come to me on conventional bioidentical therapy that do not have efficacious or therapeutic levels of conventional bioidentical hormones, and that does not provide much health benefit either.

    What’s Your Take?
    Tell us what you think of this research on bioidentical hormone therapy. Remember to check back regularly for more of these reviews from Neal’s library, and feel free to share additional articles or links to studies on bioidentical hormones.


  • November 15, 2013 9:29 AM | Christiaan Killian (Administrator)

     

    NEAL ROUZIER, M.D.

    JAMA 2013;310(17):1829-1836

    On the first day the JAMA article was released I received 500 emails from physicians and patients requesting my opinion of the article that demonstrated an increase in heart attacks and strokes in men treated with testosterone. Today is the second day and I’m afraid to turn on the computer. First of all this was an observational study that was retrospective in nature and this type of study is fraught with compounding biases that are difficult to control as expressed in the discussion section of this study. A randomized controlled trial (RCT) would have much more power than this type of study. Also the problem with an observation study is that it does not prove causation as would an interventional study in a blinded fashion. Therefore observational studies can’t prove causation as well as RCTs and what we should take away from the study is that which the researchers state in the last paragraph, that more studies are necessary before definitive conclusions can be made as to cause and effect. Also, treatment decisions should not be based solely on one study but rather on a trend of studies. Unfortunately the editorial comment section did not express this clearly.

    The discussion section of this article mentions that this is the only study that showed this adverse outcome and it was in a select group of individuals. All other studies have shown the opposite outcome, either no effect or protection against heart attacks. Since all other studies show the opposite, and one study does not negate all the other studies, and there were some biases in this study, I would suggest that we do not change anything that we do based on one study with flaws and biases when all other studies demonstrate protection against heart disease and stroke (see attached articles). And this was an observational study which has weaker power than a randomized controlled trial. I'm sure that other experts will voice the same opinion once they review the discussion section of this article as there were many biases and flaws in this study. A review of the index lists the studies that demonstrate protection against heart disease and strokes. In the “Longevity Section” that I present in the Part II course, all of the articles demonstrate improved longevity in those treated with testosterone, but increased morbidity and mortality in those men not treated with testosterone. The WHI study showed that Prempro increased heart attacks and strokes in certain individuals. Subsequent studies have proven that estradiol and progesterone, particularly in younger women, don't. Perhaps there is a confounding problem in older Veterans with cardiovascular disease that is different from other studies. However, as presented in the Part II course, every study that I review (and there are many) demonstrated a significant improvement in longevity and decreased morbidity and mortality in addition to improvement in all cardiovascular risk factors in men treated with testosterone as opposed to control groups treated with placebo (see attached studies).

    Had this study been published years ago, and all subsequent studies since then showed protection against cardiovascular disease, then this study would have probably been ignored and forgotten. However, since it is recent, then we tend to believe it and reject all the past studies that showed the exact opposite outcome. Nevertheless, one study does not negate many other studies that show opposite results and benefits. So I will log this study on the negative side for testosterone results but it is the only such study on this side. This is in contrast to all the other studies that show benefit of testosterone administration. It is interesting that this study appears now, just after I gave 2 lectures to a medical academy this past weekend in Las Vegas. The two one hour lectures were on all the studies of both estrogen and testosterone protecting against heart attacks and strokes. These reviews of the world's literature demonstrate all the various mechanisms of benefits of hormones in protecting the heart and brain against heart disease, stroke, dementia, and plaque deposition. The data and literature is overwhelming in favor of a protective effect of estrogen in women and testosterone in men. This recent study, although interesting and intriguing, does not change any of the evidence that I presented in these lectures nor does it change my treatment strategies. Until more studies demonstrate the same, I will continue to follow the scientific literature that demonstrates benefit. As per the suggestion from the authors, they state that more study is needed to evaluate these results. I recommend to patients and physicians that they continue the same treatment with both estrogen in women and testosterone in men based on all prior studies that show benefit in spite of this one negative study.

    Certain statements in the discussion section of the study deserve comment. The authors do note that other trials and meta-analyses do not demonstrate adverse cardiovascular outcomes. The trend so far in the literature has been a protective effect as trials demonstrated that testosterone therapy improves a number of intermediate outcomes and cardiac risk factors. This new JAMA study is the first and only study to demonstrate harm and should therefore be interpreted carefully in light of all the other studies demonstrating opposite results. In addition, the results of this study differ from a similar retrospective VA study by Shores et al that demonstrated a 39% reduction in mortality risk among patients treated with testosterone which again suggests caution in coming to conclusions only based on the present study. Different confounders and biases might account for the discrepancy. Multiple limitations of this study are noted by the authors that certainly can affect outcomes. All in all, it is an interesting study with unexpected results that are in discordance with all other studies and should not influence current therapy, but one that begs for more study.

    For those patients and physicians that are unfamiliar with the current literature on testosterone therapy, I have included 3 attachments that review various categories of hormone replacement. First are studies that review mortality in men treated with testosterone compared to control groups. Studies show improved survival in treated men versus untreated men. There are fewer heart attacks, cancer, and reduced mortality in men treated with testosterone (in contrast to the current study). Other studies go on to prove that low levels of testosterone increase morbidity and mortality in contrast to men with testosterone levels in the higher quartiles. Low levels of testosterone are predictive of an increase in all-cause mortality (CAD, CVD, cancer). So where would you like your levels to be? Other studies show that there was no increased risk of cardiac events in men treated with testosterone (in contrast to the current study).

    The second attachment lists all the articles that demonstrate all the physiologic benefits of testosterone administration on cholesterol, lipoproteins, insulin sensitivity, diabetes, inflammatory cytokines, endothelial dysfunction, atherosclerosis, blood pressure, memory loss, Alzheimer’s disease, mood, strength, energy, muscle mass, fat mass, osteoporosis, ED, sexual function, and all-cause mortality. Do you really want to stop the testosterone based on only one negative study? I’m not! What are the consequences of stopping or not taking it? Read the foregoing.

    The third attachment reviews beneficial effects on quality of life as well as disease protection. It is amazing the data on reduction of body fat, insulin levels, diabetes, inflammation, and vascular disease. “Testosterone serves to maintain health in every system of the body.” Levels of testosterone in the low to mid-normal range are associated with an increase in illness as listed above.” And don’t forget (pun intended) the protection against Alzheimer’s disease.

    Respectfully submitted, Neal Rouzier

    --

    Attachment 1

    Attachment 2

    Attachment 3

    --

    Read Dr. Josh Trutt's response to the JAMA article here.

    Read Dr. Mike Clark's response to the JAMA article here.

    Find out more about Dr. Rouzier here.


  • October 28, 2013 9:30 AM | Christiaan Killian (Administrator)

    When Dr. Rouzier walked into the meeting room for his Lifetime Achievement Award on October 18th, he was confronted with 110 people yelling, “Surprise!” It was no easy task keeping this event a secret from Neal during the 8 months of planning and emails to thousands of doctors, but it was truly a surprise that made an impact. As the lights came on, he was overwhelmed with a standing ovation for his achievements.It was an incredible evening of video clips, stories and what seemed like endless speeches by attendees about how their lives changed because of Dr. Rouzier. Both Neal and Carolyn received achievement and appreciation awards along with a book of letters and an array of gifts. Neal later commented it was without a doubt the happiest day of his life. A big thank you goes out to all those involved in making this an experience that will not be easily forgotten by those who attended.

    The event was held at the Green Valley Resort and Spa in Las Vegas, Nevada where hundreds of medical professionals, including doctors, nurses, pharmacists and students were able to attend as well as contribute to the fundraiser for MRSA research, a cause that is important to Dr. Rouzier.

    We appreciate those who were able to attend this event and contribute to the fundraiser for MRSA research, a cause that is important to Dr. Rouzier. We’d like to once again congratulate him on his Lifetime Achievement Award and thank him for his contributions to evidence-based medicine in the specialty of hormone replacement therapy and preventive care. For those of you unable to attend, we encourage you to watch the video shown at the event, which contains testimonials from a few of the many people that Dr. Rouzier has impacted. You can also view photos of the event, or go a step further and show your thanks by donating to MRSA Research.

    Catch a glimpse of what it was like to be there:
    Watch the Video
    See the Photos

    Say thanks once more—Donate to the cause important to Dr. Rouzier:
    Donate to MRSA Research 

  • July 10, 2013 9:36 AM | Christiaan Killian (Administrator)

     

    ALAN GABY, M.D.

    Helping patients successfully modify their dietary habits is often highly effective for preventing and treating a wide variety of illnesses and symptoms, especially when paired with appropriate supplements and other natural substances. This basic yet intricate knowledge is supported by scientific research and clinical experience that is reinforced by new studies every year. As described in Nutritional Medicine by Alan R. Gaby, M.D., unlike drug-based medical therapies that often trade negative side effects for symptom relief (e.g., osteoporosis in exchange for pain relief), nutritional medicine almost never causes serious adverse effects. To the contrary, nutritional therapies often produce positive side effects, such as “more energy, better mood, fewer cravings, better mental concentration, and less aches and pains.” To begin unraveling the intricacies of nutritional medicine, read on for an excerpt directly from Dr. Gaby’s book that provides an introduction to the practice of nutritional medicine and the synergistic effects of nutritional treatments. You can also attend CME accredited lectures on Nutritional Medicine taught by Dr. Gaby himself at the Part II and Part III Courses.

    NOTE:  The information in this post has been excerpted from Part 1 of the textbook:
    Gaby AR. Nutritional Medicine, 2011 (www.doctorgaby.com).

    Part 1 of Nutritional Medicine: Overview

     

    Why Nutritional Medicine?

    Scientific research and clinical experience have shown that dietary modifications and administration of nutrients and other natural substances are frequently effective for preventing and treating a wide range of symptoms and illnesses. Moreover, when properly administered, nutritional therapy has an excellent safety profile and almost never causes serious side effects. The nutritional approach to preventing and treating disease rarely subjects patients to the unpleasant trade-offs inherent in many drug treatments, such as statin-induced myalgia in exchange for a lower risk of having a heart attack; beta blocker-induced loss of joie de vivre in exchange for better control of heart failure; or glucocorticoid-induced osteoporosis in exchange for relief of arthritic pain. To the contrary, many of the “side effects” reported by patients who follow a nutritional program are positive, such as more energy, better mood, fewer cravings, better mental concentration, and less aches and pains.

    The Practice of Nutritional Medicine

    The practice of nutritional medicine includes several main components, the relative importance of which varies from one patient to another. For most patients, nutritional therapy starts with “cleaning up the diet” by emphasizing a wide variety of whole, unprocessed foods and minimizing intake of refined sugars, other refined carbohydrates, trans fatty acids, food additives, and other undesirable constituents of a typical Western diet. Restricting the use of salt, caffeine, and alcohol is also important for some individuals. In addition, emphasizing cooking methods that minimize the formation of potentially toxic compounds (such as cholesterol oxides, lipid peroxides, and advanced glycation end products) may be beneficial. Nutritional therapy also includes the use of a wide array of vitamins, minerals, amino acids, herbs, and other naturally occurring compounds, individualized according to the patient’s needs. This “natural pharmacopoeia” stands alongside the conventional pharmacopoeia of prescription and over-the-counter drugs. Depending on the clinical situation, these natural substances can be used as an adjunct or alternative to conventional medicine.

    Hypoglycemia / Allergy / Hypothyroidism / Candida

    In my experience, four distinct but overlapping metabolic/endocrine/immunological disorders frequently play a role in the pathogenesis of a number of chronic health conditions. Identification and appropriate treatment of these disorders is important for the successful practice of nutritional medicine. The first disorder, reactive hypoglycemia, is characterized by abnormalities of blood glucose regulation, as well as other accompanying metabolic and endocrine disturbances. Treatment of reactive hypoglycemia includes avoiding refined sugar, other carbohydrates, caffeine, and alcohol; eating small, frequent meals; and supplementing with vitamins, minerals, and other natural substances that aid in blood glucose regulation. The second common disorder is hidden food allergy. In many cases, identifying and avoiding allergenic foods can play a key role in restoring health. In many cases, identifying and avoiding allergenic foods can play a key role in restoring health. Third, a substantial minority of patients appears to have subtle hypothyroidism, despite the presence of normal laboratory tests for thyroid function. These patients benefit from treatment with low doses of thyroid hormone. Fourth is a clinical syndrome that has been called candidiasis or Candida-related complex. This syndrome is characterized by an overgrowth of, or hypersensitivity to Candida albicans. Symptoms overlap with those caused by reactive hypoglycemia, food allergy, and hypothyroidism. Treatment includes antifungal medication and dietary modifications similar to those used for reactive hypoglycemia and food allergy. Hypothyroidism and Candida-related complex are beyond the scope of this chapter.

    Individualizing Treatment

    Nutritional medicine is highly individualized, and effective treatment varies from one patient to another. For example, some patients with chronic fatigue respond best to dietary modifications such as avoiding refined sugar and eating 6 small meals per day, or identifying and avoiding allergenic foods. In other cases, the most effective treatment for fatigue is a low dose of thyroid hormone or a specific nutritional supplement, such as potassium magnesium aspartate, iron (to correct iron deficiency), or intramuscular vitamin B12 (even in the absence of vitamin B12 deficiency). Frequently, the best results are achieved with a combination of interventions.

    Clinical Assessment

    Determining which treatments are most likely to be effective for a particular patient requires a proper medical and dietary history, a good physical examination, and a working knowledge of the nutritional-medicine literature. Laboratory tests are essential in some circumstances (as in diagnosing iron deficiency), but may be of questionable validity or even misleading in other situations (as in identifying hidden food allergies or subtle nutritional deficiencies). In practicing nutritional medicine, I have rarely ordered laboratory tests other than those that might be ordered by a conventional medical doctor.

    Additive and Synergistic Effects

    A recurring theme in nutritional medicine is that combinations of interventions often have additive or synergistic effects, in that they are more effective than single interventions. For example, combinations of nutrients may be more effective than individual nutrients; the beneficial effects of dietary modifications are often more pronounced when combined with appropriate nutrients, hormones, and other natural substances; and the benefits of nutrients, hormones, and other natural substances are often more pronounced when patients also adhere to appropriate dietary recommendations. A corollary to these observations is that nutrients, hormones, and other natural substances are sometimes effective at lower doses when they are used in combination with other interventions than when they are given singly.

    Clinical observations regarding the existence of additive and synergistic effects are supported by both clinical and basic-science research. For example, anemia has been found in some studies to respond better to multiple nutrients than to a single nutrient. The combination of B6 and magnesium was reported to be more effective than either of these treatments alone in the treatment of autism. In addition, the homocysteine-lowering effect of folic acid was enhanced by the addition of vitamin B12.1 In dermatology, vitamin E has been used to increase the therapeutic effect of vitamin A. In healthy volunteers, the combination of vitamin C and vitamin E enhanced parameters of immune function to a greater extent than did either of these nutrients individually.2

    In mice with experimentally induced atherosclerosis, combined supplementation with vitamin E and coenzyme Q10 was more anti-atherogenic than was either supplement alone.In isolated rat hearts subjected to ischemia and reperfusion, various hemodynamic and metabolic abnormalities were prevented by simultaneous administration of carnitine and coenzyme Q10, but not by administration by either of these nutrients individually.4

    Possible Mechanisms

    There are a number of possible mechanisms by which dietary modifications and treatment with natural substances could have additive or synergistic effects. For example, dietary improvements might decrease inflammation and oxidative stress, thereby allowing nutritional supplements to be used for processes other than mounting an inflammatory response and quenching free radicals. In addition, certain nutrients enhance the absorption of tissue uptake of other nutrients. For example, vitamin C increases iron absorption and magnesium promotes the uptake of potassium from serum into cells. Some nutrients inhibit the degradation of other nutrients (e.g., flavonoids decrease vitamin C requirements by preventing the oxidation of vitamin C).5 6 Furthermore, certain nutrients may relieve biochemical “bottlenecks” by activating parallel pathways. For example, the conversion of homocysteine to methionine proceeds largely through a folate-dependent pathway, but it may also proceed through a separate pathway that requires betaine. Similarly, multiple biochemical pathways exist to detoxify xenobiotic chemicals, bacterial toxins, and endogenous metabolites.

    Synergy and the Art of Nutritional Medicine

    Because multiple nutritional interventions are often more effective than a single treatment, practitioners may be tempted to “throw everything but the kitchen sink” at various medical problems. However, nutritional “polypharmacy” is not without potential drawbacks, including high cost to the patient, increased time and effort involved in following the complex treatment regimens, and the possibility that ingesting numerous tablets and capsules will cause gastrointestinal or other side effects.

    The art of nutritional medicine includes being able to identify which dietary modifications and supplements are most likely to be beneficial for a particular patient, and which interventions are more likely to be ineffective or unnecessary. As with other healthcare disciplines, mastering the art of nutritional medicine requires education, contemplation, and practice. According to one of my mentors in medical school, Dr. Theodore Woodward, the better trained you are, the fewer tests you will need to perform and the fewer medications you will need to prescribe. That principle also applies to nutritional medicine.

     

    References

    1. Bronstrop A, Hages M, Prinz-Langenohl R, Pietrzik K. Effects of folic acid and combinations of folic acid and vitamin B-12 on plasma homocysteine concentrations in healthy, young women. Am J Clin Nutr 1998;68:1104-1110.
    2. Jeng KCG, Yang CS, Siu WY, et al. Supplementation with vitamins C and E enhances cytokine production by peripheral blood mononuclear cells in healthy adults. Am J Clin Nutr 1996;64:960-965.
    3. Thomas SR, Leichtweis SB, Pettersson K, et al. Dietary cosupplementation with vitamin E and coenzyme Q10 inhibits atherosclerosis in apolipoprotein E gene knockout mice. Arterioscler Thromb Vasc Biol 2001;21:585-593.
    4. Bertelli A, Ronca F, Ronca G, et al. L-carnitine and coenzyme Q10 protective action against ischaemia and reperfusion of working rat heart. Drugs Exp Clin Res 1992;18:431-436.
    5. Crampton EW, Lloyd LE. Quantitative estimation of effect of rutin on biological potency of vitamin C. Fed Proc 1950;9:355-356.
    6. Clemetson CAB, Andersen L. Plant polyphenols as antioxidants for ascorbic acid. Ann N Y Acad Sci 1966;136:341-376.

     


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