Winter 2015, Article 71

What the Heck Has Been Going on in My World?
By Mark A. Moyad, MD, MPH, University of Michigan

article #71 – Winter 2015

Note: A total of 71 (YES THAT IS 71…that’s a lot…even higher than the number of times my kids said “I am sorry and I will not do that again” and then they did that again!) times in a row (and for 16+ years!) I have written and volunteered for this newsletter. I have yet to receive any personal financial compensation or personalized classic timeless gifts such as PAACT complimentary lifelong mental health therapy for Dr. Moyad after Michigan lost to Michigan State in football on the last play of the game when we were all set to beat those evil guys and their “I am always serious and in a cranky mood” coach (although the guy is really a genius and needs to go coach another team far away, for example some team at the North Pole or Russia, because he is making me crazy) so I can quit seeing him finally semi-smile when he beats Michigan!!! At least it took a miracle to beat Michigan this year and that will be true in the future. Also, by the time you read this newsletter the Mighty Michigan versus the Overrated Ohio State Football game will be over and if we don’t beat those dudes, I’m going to need twice as much mental health therapy so PAACT should get ready to pay for my medical needs ASAP! However, if Michigan can beat Ohio State this year, then I’m going to be in a VERY HAPPY PLACE!!! In fact, if Michigan beats/upsets Ohio State this year, please send me beer and money, because I will have deserved it and if they lose please send me beer and money because I will deserve it and need it!

I WANT TO THANK YOU AGAIN FOR CONTINUING TO MAKE “THE SUPPLEMENT HANDBOOK” – my semi-new book a best seller. YEAH!! THANK YOU!!! Second, if you have not picked up a copy please get one on Amazon.com (the very cheapest place to procure a copy) to support my “Just for Men” fund because my hair is turning even more gray and thin with every issue of PAACT (because I’m getting older, not because I’m experiencing more stress – except when Rick Profit from PAACT sends me an email every 2.5 months stating “your column is due this Friday.” Then I experience stress and I place a small picture of him on my office wall and throw darts at it – especially trying

to hit his mid-section, but then after I turn the column in I feel bad that I did this and take his picture down, but I never tell him that I have this nefarious regular habit and I am sure there is no way he will ever find out that I temporarily throw darts at his picture – I mean how could he find out that I do this on a quarterly basis???)! And, for about 19 bucks (the cost of only 10 two dollar candy bars or a few boxes of Girl Scout cookies – I like the mint ones by the way) you get 512 pages of material on over 100 medical conditions and when not using this amazingly big book it also functions as a football or a Discus.

BREAKING NEWS!!!

325) HILLARY CLINTON EMAILS & President Bill Clinton and Monica Lewinsky! (Actually have nothing to do with this article I just wanted to get your attention).

MY TRIP TO ITALY AND WHAT IT MEANS FOR YOU = COFFEE HAS ANTI-CANCER EFFECTS (Maybe) AND POMEGRANATE DOES NOT???! HEY, THIS IS 3 ARTICLES IN ONE! A TRIFECTA! WHAT A DEAL!!!

(Reference: Moyad and Delta Airlines; Guercio BJ, et al. J Clin Oncol 2015, released early on-line; Liu H et al. Nutr Cancer 2015;67:392-400. & Discacciati A, et al. Ann Oncol 2014;25:584-591).

BOTTOM LINE

Italians drink a lot of coffee and now caffeinated, low or no calorie coffee has some preliminary evidence that it could

Cups of coffee with smoke and coffee beans on old wooden background

reduce the risk of colon and prostate cancer returning after treatment OR this positive evidence only exists because some men that drink a lot of coffee harbor a lot of other healthy behaviors. Regardless this is pretty cool stuff! And, pomegranate juice/extract? Let’s just say it’s not been a good year for pomegranate and prostate cancer evidence, especially when compared to placebo.  OUCH!!!

WHAT ELSE DO I NEED TO KNOW?

I just returned from a brief working trip that took me throughout Southern Italy – I know…life is really tough at times, but someone has to be Mark Moyad. Now I am semi- or actually fully addicted to coffee because in Italy it is ubiquitous, you can’t escape from it, which is kind of like those lawyer ads on TV that promise you big money if you just take someone to court, and they/lawyers do not get paid unless you get paid (wow!). That’s so kind! Expresso, cappuccino, café Americano …yummy for my tummy. I learned about all of them by trying them over and over again! Man, I had more energy than a 16-year old kid getting his driver’s license and a new car on the same day! However, wha t was really incredible is that I saw no one – not a single person in Italy use a “to go” cup or simply walk down the street drinking coffee – not a single person in any of the many cities I visited?! What the heck is going on? These well-dressed Italians (Man they look good even in the early morning…I mean who looks that good in the United States so early in the morning…apart from my wife of course – BOOM! Man, I am as smooth as a baby’s bottom) stand or sit in a café and drink and talk and then move on with big smiles on their faces.

Now it appears that coffee is healthy for you? Perhaps it’s not the coffee but the underlying comprehensive healthy behavior of the coffee drinker in some of these countries. They appear to regularly socialize, relax, remain strong spiritually, walk constantly, and eat very healthy diets, but only in small to moderate portions. For example, I ordered a crab-stuffed ravioli in Rome, a pizza in Naples, Caprese salad in Sorrento, and anchovies in Amalfi that I swear in every case were considered a main course, but were so small that in America they would not even qualify as an appetizer! In other words, the portion sizes were so tiny! I mean even their soda drinks were tiny! This must be the secret of the Mediterranean diet or perhaps it’s the fact that I dumped gallons of olive oil on everything because right now the oil is so fresh and yummy with bread and veggies and meat and fish and _______ (insert your favorite food)! You could almost drink the olive oil straight because it was so fresh in Italy! And, olives themselves were so fresh that I ate a plate of them at every meal! Just call me “Mayor of Olive City” because I LOVE to EAT OLIVES (get it…olive is like saying “I love” – in fact it you mouth the words “olive juice” from a distance to a friend or relative they actually think you are saying “I love you.” Try it sometime, it’s funny!).

Back to my story! Multiple new human (not mouse or rat) studies are also suggesting that coffee (especially the low or no calorie caffeinated type) itself has some anti-cancer/anti-inflammatory properties and could reduce insulin over-exposure, which means not only as a preventive, but also as a way to reduce cancer recurrence. Wow! Is this possible? I mean coffee actually does have some interesting compounds like “chlorogenic acid” that could be healthy! And, in a recent American colon cancer study of patients that had been treated for colon cancer the results were pretty good and got my attention (even though I never drank coffee before except one time in high school before I had to stay up all night for an exam that I think I ended up failing – thanks a lot coffee). In a recent study a total of 953 patients with stage III colon cancer during and 6 months after adjuvant chemotherapy who were prospectively followed over time and the dietary intake of a variety of foods and beverages were self-reported and recorded. Patients ingesting 4 cups/day or more of caffeinated coffee experienced a significant (p=0.002) 52% reduction of colon cancer recurrence or mortality (HR=0.48) versus never drinkers. Non-herbal tea and decaffeinated coffee were not associated with a clinical benefit. Greater coffee intake could be correlated with a significant reduction in colon cancer recurrence and mortality in patients with stage III colon cancer. I wanted to ignore past data that had been primarily retrospective and observational through the years but the accumulating data in cancer has become difficult to ignore.

Yet, is it really the coffee or the average healthy behavior of the coffee drinker that is the secret? It doesn’t even matter because the message of eating a healthy diet but in small portions and moving more and staying skinny is just part of the theme of the coffee drinker. If many Italians would just quit smoking they would live even better and longer, this is what they can learn from us in America (not smoking). Although, many Italians would then start struggling with massive weight gain, which has begun to occur. My trip to Italy was a beautiful educational experience that reinforced some of the similar cultural secrets to a better and/or longer life that I have witnessed from traveling throughout the world from Singapore to South Africa to South America over the past 30 years. However, the smoking part is devastating because although smoking DEFINITELY helps you stay skinnier it also increases the chances of making your life worse while you are living it and ending your life earlier and exposing all those arounds you to this carcinogen. DISGUSTING! In fact, a few times my wife and I walked into a store and were going to spend an obscene amount of money (aka 20-30 dollars) and the store employee or store itself smelled so much like tobacco we had to turn around and leave the store!

Interestingly, at the time I was writing this column, suffering from massive acid reflux and sleepless in Ann Arbor, moments from drinking coffee, there was another research study from the National Cancer Institute (aka NCI) that was published (Loftfield E, et al. Cancer Epidemiol Biomarkers Prev 2015;24:1052-1060.), which suggested that coffee is potentially associated with lower death rates from colon, endometrium, liver and prostate cancer and that improving insulin sensitivity and decreasing inflammation may be the reasons for this potential benefit. So, NCI researchers decided to measure blood levels of 77 immune system and inflammatory markers in over 1700 individuals. Coffee drinkers appeared to have lower blood levels of several inflammatory blood tests! Man, this is getting weird and awesome (kind of like watching your parents trying to operate an I-phone)! And now the bad news that has to do with another highly touted anti-cancer beverage (please read the next paragraph)!

Despite over 10+ years of excitement in the area of pomegranate extract or juice there were few long-term placebo comparative trials and this is what always worried me. It was also worrisome that when someone ingested pomegranate supplements (juice, pills…) there were no significant beneficial changes in weight/waist size, blood sugar, blood pressure, or LDL or “bad” cholesterol. HEART HEALTHY = PROSTATE HEALTHY = Moyad circa 1999 and beyond. It was for these and other reasons I have for years commented that pomegranate could be getting WAY, WAY too much hype and might not do well overall in more rigorous clinical trials and I predicted in my SUPPLEMENT HANDBOOK (available now on Amazon.com = shameless plug #345) that it would fail to work in bigger and better studies. Many people/experts that will remain nameless (until I see them and remind them that they were wrong), pushed the pomegranate agenda aggressively and I do not believe this was helpful. Regardless, here are the issues – after 3 high quality trials it seems that pomegranate is not working much better than a placebo for most individuals. One study was for advanced prostate cancer patients (Stenner-Liewen F, et al. Journal of Cancer 2013;4:597-605.), another was for patients having surgery for prostate cancer (Freedland SJ, et al. Cancer Prev Res 2013;6:1120-1127.), and the third and more recent major trial was for men with rising PSA after primary therapy (Pantuck AJ, et al. Prostate Caner and Prostatic Disease 2015;18:242-248). This is not good news for pomegranate juice or other products derived from the pomegranate, but I have always believed that eating a real and NATURAL (can I use that dirty word) POMEGRANATE will always be healthier than drinking the juice or taking the supplements. Now, that’s a clinical trial I would like to see….pomegranate juice versus supplements versus a pomegranate itself in a CAGE MATCH for a FIGHT WHERE WINNER TAKES ALL!!! My money is on the ignored low cost pomegranate fruit to win in a knockout in the second round!! Regardless, let me remind you what a “natural” pomegranate gives you and why it’s always a healthier choice (in my opinion) versus the pills or juice. It’s because there is approximately 3.5 GRAMS OF FIBER in a serving of pomegranate seeds, which is very high compared to many fruits and helps control the amount of sugar absorbed from the juice. And, if you remove the fiber and just keep the juice then what do you have apart from a lot of liquid sugar? I’m not sure what you have, this is why I put a question mark at the end of the last sentence.

Now, let me ask you 5 questions that are more important than any pomegranate or supplement product or almost any product on the market. PLEASE INSERT YOUR NUMBERS BELOW AND THEN BRING THEM TO ME WHEN YOU SEE ME AT A LECTURE, MEETING, BAR, OR A MCDONALD’S NEAR YOU!

1. Do you know exactly your weight/waist size?

2. Do you know exactly your last LDL cholesterol (aka “bad cholesterol”) value?

3. Do you know your blood sugar value?

4. Do you know your blood pressure numbers?

5. Do you know why Coach Jim Harbaugh at Michigan will win the national title in college football in 2017 and 2018 (rhetorical question…of course the answer is “because he is Jim Harbaugh the most brilliant coach in the history of college football” and because he went to grade school with another fabulous person named Mark Moyad…no kidding “St Francis of Assisi” in the 1970s, I think…it was while ago)?

Anyhow, let’s conclude this section on coffee by reminding you that the next time you go to Starbucks just order a tall medium or light coffee with no extras and that’s only 5 CALORIES!! If you don’t like coffee just order their OATMEAL (only 160 calories and 4 grams of fiber and virtually no sugar and 5 grams of protein) with a dash of milk and no extras – you will like it and your colon and prostate and heart and your sexual organs (I was going to use that “p” word for example, but PAACT is a family newsletter so using the word “penis” would have been inappropriate, so whenever you see the letter “p” by itself it means “penis” or it could also mean “PAACT” I guess…you decide) will say thank you very much for consuming such a healthy product!

326) What I ordered at McDonald’s the other day!

(Reference: McDonalds in Ann Arbor, MI or Detroit Airport or Denver, Colorado or coming to a McDonalds near you)

BOTTOM LINE

Fast food restaurants get a lot of criticism, as they should, because many items are as unhealthy as a swift kick in the groin area that just keeps on hurting, but once in a while they come up with a delicious low calorie option that should be given credit! So, let’s give them credit for inventing the EGG WHITE DELIGHT McMUFFIN! Hip, Hip, Hooray, it may actually be good for your waist and hip bones!

WHAT ELSE DO I NEED TO KNOW?

What tastes amazing, costs very little money, and only has 250 calories but also has 18 grams of PROTEIN (that’s a lot) and 7 grams of fat, zero trans-fat, only 30 milligrams of cholesterol, 1 gram of dietary fiber, 3 grams of sugar and 230 milligrams of calcium (that’s a lot) and again did I mention it tastes VERY YUMMY AND AMAZING AND IT MAKES ME FEEL FULL!!! IT IS THE EGG WHITE DELIGHT McMUFFIN!!! HIP, HIP, HOORAY!!! HIP, HIP, HOORAY!!! HIP, HIP, AND IT’S GOOD FOR YOUR HIP(s)!

Wait, Dr Moyad you are actually pushing fast food and McDonalds, which has arguably kept most cardiologists in business over the past few decades?! So, what’s the catch with this newer food or breakfast item besides the fact that McDonalds invented it? There is a catch – it contains 760 mg or 31% of your daily intake of SODIUM – YIKES!!! So, of course there’s a catch, but if this is all that you eat for breakfast and you regularly watch your sodium intake or in reality increase your potassium intake then WHO THE HECK CARES!!! I LOVE THIS NEW BREAKFAST ITEM!!! TRY IT AND AFTER YOU LOVE IT SEND ME A GIFT CERTIFICATE TO MCDONALD’S FOR CHRISTMAS or HANUKKAH or whatever you celebrate! Anytime is a good time to buy Mark Moyad a gift!!!

327) Why calcium supplements are not needed anymore for most people (exceptions include those on osteoporosis prescription drugs and steroids long-term like prednisone and those that rarely consume foods and beverages with calcium, which is hard to do by the way…did you see the amount of calcium in the McDonalds item from the previous news story Moyad discussed?)!   (Reference: Moyad MA. The Supplement Handbook-best book in world)

BOTTOM LINE

Calcium supplements (with or without vitamin D) have many risks including: increasing the risk of kidney stones, constipation (Hey, wait slow things down – get the joke…constipation? Really?), inflammation of the throat, swallowing problems, and even heart disease (controversial, but concerning). Additionally, there’s so much calcium in food and beverages today that people are being over exposed to it. The goal is to normalize your intake of calcium and vitamin D to prevent falls but there’s no reason to get excess amounts of calcium and vitamin D. I have written about this many times but there’s new information on the subject so let’s discuss it.

WHAT ELSE DO I NEED TO KNOW?

If you want to learn about the highest sources of calcium in foods and beverages go ahead and GOOGLE IT (or in reality I say “MICHIGAN IT” because one of the founders of google went to the University of Michigan and he loved it as much as Tom Brady loved it, because it’s the greatest school in the world.

I’m not biased at all….oh and did I mention it’s the greatest school in the world and Tom Brady went there and loves it!).

Calcium is so replete in multivitamins (heck I saw one the other day with 500 mg of it per multivitamin pill), food and fortified beverages today it has become easier than ever before to attain the recommended 1000-1200 mg per day (1000 mg in 19-50 year old males and females, 1000 mg in 51-70 year old males, 1200 mg in females 51 years and older and males 71+ years). The table on this page is a representation of how much easier it is to reach the RDA goal of calcium without having to take separate calcium supplements.

In fact, in the largest dietary supplement trial ever conducted on calcium supplements (WHI) the baseline intake of calcium from foods, beverages and supplements was already approximately 1150 mg/day of calcium before randomization to the calcium or placebo groups! In other words, many of us are already getting too much calcium or enough calcium.

The Women’s Health Initiative (WHI) was a double-blind, placebo-controlled clinical trial and the largest U.S. clinical trial to address the issue of calcium and vitamin D supplementation. This trial included 36,282 postmenopausal U.S. women who were to ingest 1000 mg elemental calcium carbonate plus 400 IU of vitamin D3 (OsCal® brand of calcium supplements, GSK Company) or placebo for 7 years. The average BMI was 29 (almost obese) and there were a greater number of obese versus overweight women in the trial, which interestingly appears to reflect the current U.S. population. The primary endpoint was the reduction in hip fractures, and secondarily total fractures and colorectal cancer. Calcium and vitamin D supplementation significantly increased hip and total bone mineral density (BMD) versus placebo (p<0.01), but there was no overall evidence to suggest a reduction in hip or total fracture risk. There was an increase in kidney stone risk and there were no impacts on cardiovascular events or colorectal cancer risk. This study, the largest of its kind, continues to suggest that normalization or increased calcium and vitamin D supplementation could improve bone mineral density and may have an impact on hip fracture risk but arguably only in those individuals that are not getting enough calcium and vitamin D. But, keep reading because you might be surprised as to how calcium and/or vitamin D might be reducing the risk of bone fractures, if they do at all.

A recent extensive analysis of the calcium and vitamin D supplementation data from the U.S. Preventive Services Task Force or USPSTF (the same group that now discourages PSA screening…love them or hate them) found treatment of vitamin D deficiency in some asymptomatic person might prevent falls (not fractures). They concluded their findings the following way: “Treatment with vitamin D, with or without calcium, may be associated with decreased risk for mortality and falls in older or institutionalized adults. Vitamin D treatment did not reduce fracture risk…” This is a critical initial finding from the research, which in my opinion also suggests cancer patients should normalize their calcium and vitamin D intakes to maximize the benefits of bone loss prevention and especially FALLS, which could lead to an increased risk of fractures. And, there is enough evidence from these past reviews of the data that calcium and vitamin D are also important for muscle health and coordination.

Additionally, most major trials of drug interventions to prevent bone loss and fractures in cancer patients, including denosumab (Xgeva®) and zoledronic acid (Zometa®), utilized some form of calcium (1000 mg per day) and vitamin D supplementation (400 or more IU per day) or normalization of intake to ensure adequate responses to these bone medications.

Thus, when these drugs received FDA approval in breast and prostate cancer it was due to phase-3 trial evidence of the drug with the use of calcium and vitamin D in combination (not by itself) to normalize daily intakes. So, how much vitamin D is enough? Well, the Institute of Medicine (IOM) has done a good job of simplifying the requirements. Age 18 to 70=600 IU of vitamin D a day and from the age of 71+ then 800 IU per day! That’s it!!!

Now, without going through all the side effects of taking calcium dietary supplements, which I have covered adequately in past PAACT issues (along with which calcium supplements are better or worse or pose less of a risk of kidney stones…) there is now a new issue “PILL ESOPHAGITIS” (inflammation of your food pipe). Pills come with unique side effects and although life-saving in many cases another reason not to ingest a pill unless needed is due to “pill esophagitis.” This is well-known in the pharmaceutical industry, for example, and often it is due to patients not drinking enough water or standing up when ingesting a pill (for example this is why all osteoporosis pills come with these instructions and warnings). The symptoms of pill esophagitis include difficulty swallowing, pain on swallowing and retrosternal pain. Yet, dietary supplements can also cause pill esophagitis and esophageal ulcers, so the concern or at least recognition over this side effect in the supplement industry should immediately match that of the pharmaceutical industry. Increasing awareness of dietary supplement side effects allows for the identification of pill side effects unique to the industry itself, especially when compounds such as “silicon dioxide” (aka “sand”) are utilized in some products to a large extent. Recently, recognition of an increased risk of 100% silicate based kidney stones can occur in products that contain ample amounts of this compound. And, this is just one of many compounds uniquely utilized in pills, especially supplements that were believed to be inert in humans.

However, back to the famous/infamous calcium supplements for a second because some are as large as the front door of your house (THAT IS A BIG FRONT DOOR Dr. Moyad). Recently there was a report that suggested over 23,000 emergency room visits occur PER YEAR because of dietary supplements (Geller AJ, et al. N Engl J Med 2015;373:1531-1540)! YIKES!!!! I actually think this number is a lot higher for many reasons that would be boring to you and would just take up a lot more space and I am getting tired typing (I have fingeritis, I wonder if I should call one of those lawyers on TV and hold PAACT responsible for this clear cut disease caused by PAACT)! Anyway what got missed in the publicity around this paper that mostly focused on weight loss supplements or energy products was the finding that “AMONG ADULTS 65 YEARS OF AGE OR OLDER, CHOKING OR PILL-INDUCED DYSPHAGIA” (problems with swallowing) was responsible for 38% of all those emergency department visits in this age group!!! And, more than half of the swallowing problems (54%) with pills from this study from emergency room departments around the U.S. were due to “CALCIUM PRODUCTS/SUPPLEMENTS!!!” This is another big problem with calcium supplements today because like multivitamins they are becoming too big or are too big! In the pharmaceutical world the FDA recommends that a pill should not be greater than 22 millimeters, but with supplements there is no recommendation or rule! GEESH!!

328) Fiber Primer and why getting more dietary (not supplemental fiber) is one of the keys to internal anti-aging! So, it’s a form of BOTOX®? YES!!! But, wait you have talked about this before in the PAACT newsletter and readers are sick of hearing about it! Nope! There is breaking news and new information on it and it has to do with PSA screening?! And, how about some of my favorite BOTOX jokes you have never heard and why exercise keeps things flowing and lets you sleep at night if your prostate is large and in charge?

(Reference: Moyad MA, 2015)

BOTTOM LINE

Consume more (soluble and insoluble) dietary fiber (20-30 grams/day or 14 grams per 1000 calories consumed), especially from food sources. “Fiber is nature’s internal Botox for the human body” (Moyad Circa 2014) and both soluble and insoluble fiber have unique and synergistic benefits when found together (as in most healthy dietary sources). OH BOY HERE GOES MOYAD AGAIN TALKING ABOUT FIBER!!! That’s correct! I have mentioned much of these benefits before, but let’s review again and add some new information! So, let’s get things moving (get it?) and talk fiber!

WHAT ELSE DO I NEED TO KNOW?

General and numerous health benefits are derived from consuming dietary fiber that have been well documented and include reductions in the following:

• Coronary heart disease (CHD) risk

• Stroke

• High blood pressure

• Diabetes

• Obesity

• All-cause mortality=death from all•causes (which is a good thing)

For example, a pooled analysis of past cohort studies of dietary fiber for the reduction of CHD (coronary heart disease) included research from 10 international studies and included the U.S. Over a period of 6-10 years of follow-up, and after multivariate adjustment it was revealed that each 10 gram/day increase of calorie-adjusted total dietary fiber was correlated with a 14% reduction in the risk of total coronary events and a 27% reduction in risk of coronary death. These findings were similar for both genders, and the inverse associations occurred for both soluble (also known as “viscous”) and insoluble fiber (both are found in most healthy food sources of fiber compared to commercial pills and powders that normally just or primarily contain “soluble” fiber).

Past studies have not observed a consistent benefit with one class of fiber over the other (soluble or insoluble). Recent large U.S. and other international studies have even found more striking overall potential benefits for consuming more dietary fiber. For example, the NIH-AARP U.S. prospective cohort found not only a lower risk of dying from cardiovascular, respiratory and infectious disease with greater intakes of fiber but a significantly lower risk of dying younger (“total death”) in men and women. This study may represent a major shift into the research behind fiber intake because now the potential health impact may be so much larger than first realized since reductions in the death rates of some of the largest causes of mortality may occur with greater fiber intakes.

Even minor additions of some commercial fiber sources (to your overall large dietary fiber intake) can positively impact medication dosages. A total of 15 grams of psyllium (Metamucil for example) husk supplementation daily with a 10 mg statin (simvastatin) was demonstrated to be as effective as 20 mg of this statin by itself in reducing cholesterol in a preliminary placebo-controlled study of 68 patients over 12-weeks. Although adding soluble fiber from commercial products appears to be safe and synergistic with cholesterol lowering medications, the first choice of increasing fiber intake should be FOOD SOURCES based on cost-effectiveness and simplicity. I’m not a big fan of Metamucil in large amounts, but if you need a little help getting to your daily fiber total, then Metamucil is an option.

More benefits should be emphasized so let’s do this – a meta-analysis of 24 randomized placebo-controlled trials of fiber supplementation found a consistent impact on blood pressure reduction. Supplementation with a mean dose of only 11.5 g/d of fiber reduced systolic blood pressure by –1.13 mm Hg and diastolic pressure by –1.26 mm Hg. The reductions were actually greater in older and more hypertensive individuals compared to younger and normotensive participants. Recent international studies continue to support the modest reduction or control in blood pressure with greater intakes of dietary fiber.

How much fiber should patients be consuming daily? Daily intakes of total fiber in the U.S. and many other Western countries is approximately 10-15 g/d, which is approximately only half or even less than half of the total amount consistently recommended by the American Heart Association (AHA) and American Dietetic Association (20-30 g/d) for adequate overall health. Another perspective on recommended fiber intake for children and adults is that for every 1000 calories of food and beverage consumed there should be at least 14 grams of fiber consumed.

Dietary fiber from food is easily achieved by low cost sources of soluble and insoluble fiber. For example, I often tell patients to consume a third of a cup of a bran cereal such as All-Bran Buds several times a week, which is approximately only the size of 1-2 liquor shot glasses, with flaxseed and some fruit, and before they leave the door in the morning approximately 20 grams of fiber will have already been ingested toward the 25-30 gram goal! Low cost fiber sources such as flaxseed can provide potentially numerous heart healthy and overall health benefits. Perhaps the low-cost and non-commercialization of this product on a large-scale has led to the lack of adequate education that I’ve observed on this product. Flaxseed is one of the highest plant sources of heart healthy omega-3 fatty acids, and chia seed is arguably the largest plant source of fiber and omega-3, and both of these additions to the overall diet would be ideal. Also, the
original Fiber One® cereal contains 14 GRAMS of fiber in just a half a cup! WHAMMMO! This definitely keeps the train moving!

Interestingly, the preliminary clinical trial data on ground flaxseed (average of 30 grams or 3 rounded tablespoons per day) in other hormone mediated cancers such as breast cancer has been as or more impressive (reduced proliferation rates or Ki-67, which is a marker of potential cell or abnormal cell growth). Thus, it shouldn’t be a surprise that preliminary data of flaxseed in prostate cancer is also impressive and similar to some of the breast cancer observations. Flaxseed oil also has preliminary data against cancer, but this and other oils are a large source of calories (120-130 calories/tablespoon) and contain no fiber so rarely have I recommended them over low cost flaxseed powder (similar to the real whole non-processed fruit versus the fruit juice debate mentioned earlier).

Overall dietary fiber intake (again not pills or powders) continues to garner evidence as a method of cancer prevention. Multiple mechanisms are potentially involved with this fiber benefit including:

• reduction in by-products of male and female hormones that could stimulate cancer growth

• reduction in insulin and growth factors/mitogens,

• reduction in inflammatory compounds potentially via production of short-chain fatty acids when fibers are fermented in the colon by flora and products of fermentation such as butyrate and propionate enter the circulation.

• plethora of heart healthy changes altering cancer risk/recurrence (lower weight/waist, reduced cholesterol and blood sugar…)

Still, fiber itself appears to have become overtly commercialized, and in my experience some patients are turning primarily toward powders and pills to solve their fiber deficit, and this is not only costly, but also provides primarily small amounts of soluble fiber that make it difficult to reach total fiber goals utilizing only these sources. For example, I often ask audiences and students how many fiber capsules/pills are needed to be consumed daily to obtain just 20-30 grams of fiber, and the answer always seems to provide adequate shock value (the answer is 30-50 pills a day or more depending on the commercial source)! A bolus of only soluble fiber without insoluble fiber can also create excessive bloating and other gastrointestinal issues because soluble fiber is utilized by gut bacteria and then subsequently converted to gaseous compounds (aka “passing gas”).

Processed soluble fibers abound today in protein bars and cookies and these items need to be avoided not only for a lack of evidence but again gastrointestinal discomfort with moderate to high intakes. Research continues to support the overall and heart healthy health benefits of fiber, especially when it’s primarily derived from food sources, because these sources also provide a unique and optimal balance of soluble and insoluble fiber. Another comprehensive list of dietary fiber benefits are found in the table on this page (see table) and this is why I often tell patients that “nature’s greatest internal Botox” has to be dietary fiber! The plethora of internal anti-aging effects it provides is noteworthy, from preventing cholesterol and glucose changes to preventing hemorrhoids, and it’s easy to forget that humans don’t just age externally but internally with time. Botox for cosmetic anti-aging is attention grabbing but why isn’t fiber just as notable for preventing internal aging?

I find it interesting that most fruits, veggies, beans, bran, oatmeal and other dietary sources of fiber are primarily an equal mix of soluble and insoluble fiber or insoluble fiber actually predominates over soluble in these products, while again most commercial products are basically almost all soluble fiber. They are both needed to improve overall health (Yin and Yang). The reason one can consume 2 medium apples (about 10 grams of fiber total) without experiencing significant bloating, gas or discomfort is the majority of the fiber is insoluble (about 30% soluble). Again, the reason one cannot consume a large bolus of processed or commercialized fiber supplements or powders is that the vast majority is soluble fiber.

Now, you think all of this information would be enough to make you run out and start gobbling (Is that even a word???)

It is on Halloween….bad joke…like most of my jokes) up a ton of fiber! Still, there is another reason to do this and this is the most surprising of all! You may remember the U.S. study called “PLCO” that demonstrated no benefit to general PSA screening and the USPSTF used this information to no longer recommend PSA screening. After that point all heck broke loose and people started arguing back and forth on whether or not PSA screening should be recommended or not. It was kind of like Republicans and Democrats arguing back and forth and not getting anywhere, which is what happens only 365 days a year (they get things done on the other days of the year). Yet, the USA PSA screening study known as “PLCO” was a well done study not just in terms of asking the screening question, but perhaps more importantly answering other important questions on diet and exercise and this is what gets missed or no one knows about! So, what other findings occurred in this famous study that hardly received any media attention. Here is one conclusion of a finding that was also uncovered in the PLCO study and I quote: “This large, prospective study within a population-based screening trial suggests that individuals consuming the highest intakes of dietary fiber have reduced risks of incident colorectal adenoma and distal colon cancer and this effect of dietary fiber, particularly from cereal and fruit, may begin early in colorectal carcinogenesis.” (Reference is Kunzmann AT, et al. Am J Clin Nutr 2015;102:881-890). THAT IS INCREDIBLE!!! So, while all these folks run around and argue whether or not an otherwise healthy man should be screened for prostate cancer, the same study that helped generate this controversy found that DIETARY FIBER (not fiber from pills) found a potential large reduction in colon cancer or precursors to colon cancer-premalignant lesions with fiber! Amazing! Okay, tell me more Dr. Moyad! Tell me more! Okay I will and quit yelling at me with exclamation marks!

In the same PLCO clinical study that generated so much controversy with PSA screening and found a potential great benefit with fiber, also found another potentially incredible benefit with physical activity or exercise that few people know about and again why these researchers did such an incredible job! Here is what they found: “we did find strong and significant associations between physically active lifestyle and nocturia….Combined with other management strategies, physical activity may provide a strategy for the management of BPH-related outcomes, particularly nocturia.” (Reference is Wolin KY, et al. Med Sci Sports Exerc 2015;47:581-592). SEE IF YOU UNDERSTAND THIS INCREDIBLE FINDING! The same study that generated the PSA controversy and found that dietary fiber could be colon healthy also found that exercise could reduce the risk of getting up at night to urinate (NOCTURIA) when a man has prostate enlargement or BPH! This is amazing!!!

In the meantime, it you are not convinced that you should be more physically active and consume more fiber you could instead pay a ton of money for the real BOTOX. Ahhh, yes the real BOTOX, which is really expensive and comes with many jokes such as:

• “People tell me that Botox is way too expensive but I just met 10 people who paid for the treatment and they didn’t look surprised!”

• “There was some major recent controversy over Botox injections but these stories never seem to make the headlines!”

Okay, that’s it! I actually don’t have any good Botox jokes, but I don’t know how to use an iron so I did inject my favorite shirt with Botox before my last talk so that there would be no wrinkles in it – Ouch! That was bad!

329) Over the next 2 years there is a good chance there will be a new Shingles vaccine and it could be one of the best preventive vaccines ever invented! Keep asking your doctor about it!

(Reference: Himal L, et al. N Engl J Med 2015;372;2087-2096)

BOTTOM LINE

The company GSK has a new shingles vaccine and you should ask your doctor about it over the next year or two. Cross your fingers! If this gets approved it could be incredible because it would be over 97% effective for all age groups from 50 and older! The current shingles vaccine is not that great especially as you get older it gets weaker and weaker. However, this is not the case with the GSK vaccine!

WHAT ELSE DO I NEED TO KNOW?

The current shingle vaccine (Zostavax®) isn’t that great as you get older, but it’s all we have right now! For example, it’s 64% effective for those in their 60s but when you are age 70 and older it’s only 38% effective compared to 70% effective for those ages 50-59 years! So, we can do better and better may be right around the corner! A new vaccine that may hit the market in 2017 is currently MORE THAN 97% EFFECTIVE REGARDLESS OF AGE!!! THAT WOULD BE INCREDIBLE! Notice how I like the word “incredible” because it is incredible. GSK completed a study in 2015 with more than 15,000 patients age 50 and older (some 80 years and older). Currently only about 1 out of 4 individuals age 60 and older get the currently available Zostavax vaccine, but if this new one becomes available, I hope we get close to 100% of the people that need it get vaccinated. What’s the catch with the new GSK vaccine if it becomes available? Well, the study was over about 3 years, so long-term, researchers are not sure if the results will continue to be this amazing. Also, you will need 2 shots separated by 2 months when or if you get it. Still, if these results stand then I wouldn’t hesitate to get this vaccine when it comes out, also because side effects are not greatly different compared to a placebo vaccine.

And, now another new study from Sweden or as I like to say “Svvvvvveeeden” (because it sounds so much cooler) continues to demonstrate an increased risk for stroke and other unpublicized problems when getting Shingles! So, yes I do think the Shingles vaccine will eventually demonstrate that it can prevent cardiovascular disease including shingles! The risk of stroke and sepsis (serious infections) were significantly higher in the 12 months after getting shingles from this population study of over 13,000 cases of shingles! Yikes! Some researchers theorize that the shingles virus can actually infect arteries in the brain and others suggest that it creates a full body long-term inflammatory response that increases the risk of a number of cardiovascular problems. It’s interesting that in this recent study it was found that even younger individuals had a much larger risk of stroke if they had shingles. This is scary stuff and another reason why I am a BIG, BIG FAN of the current and future shingles vaccines. Finally, I think the potential for another benefit could occur with shingles and that is a reduction in the risk of COLD SORES! What? Moyad has lost it (but he never had “it”) and thinks the future shingles vaccine could prevent cold sores?! Yes, because cold sores are in the herpes virus family, which is a large family of viruses that also includes shingles. In fact, there are several studies now showing that there is an increased risk of being infected or bothered by one condition if you already have the other and vice versa. HOW MUCH FUN IS THIS STUFF (not shingles or cold sores but just this information is fun right?)!!!

I just love to talk about cold sores and shingles especially at the family dinner right after the family begins to take their first bite! It’s really great watching everyone get sick or look horrified at the table (reminds me of the holidays). You should try this some time, it will definitely get the attention of everyone and it’s also educational!

THAT’S ALL FOLKS…. See you in the SPRING, when I will write about many other serious issues and give timeless advice in the next newsletter, such as: why it’s never good to carry a heavy, hard to manage chainsaw in a crowded male nudist camp, it’s never good to talk about shingles and cold sores at the dinner table, it’s never a good thing to hear a surgeon say “I can’t find my glasses” right before you receive anesthesia as a patient, it’s never a good thing to take a laxative, a sleeping pill and a Viagra at the same time, and why it’s never good to tell someone you love them and then burp loudly.




Fall 2015, Article 70




Article #69, Summer 2015

What the Heck Has Been Going on in My World?
By Mark A. Moyad, MD, MPH, University of Michigan
article #69 – Summer 2015

 

A total of 69 times in a row (and for 15+ years!) I have written and volunteered for this newsletter, and I have yet to receive any personal financial compensation or personalized classic timeless gift s such as: a PAACT complimentary concert tickets to see a Justin Bieber concert or a back stage pass to meet Miley Cyrus (wait I don’t even want those things), a package of Double-Stuff Oreo Cookies (amazing), McDonalds French Fries (doubly amazing), Five-Guys Junior Hamburger (triply amazing) or a Del Taco baby Burrito with extra green sauce (quadrupley amazing) and finally a free PAACT state-of-the-art elliptical or treadmill machine and church pew because after I eat all that stuff (aka junk food that tastes incredible) I will need a few hours to run it off and pray real hard that it does not stick to my belly, coronary or penile arteries forever!” YIKES!!!

FIRST AND FOREMOST I WANT TO THANK ALL OF YOU FOR MAKING “THE SUPPLEMENT HANDBOOK” – my new book a best seller in the winter and spring of 2015! AN AMAZON BEST SELLER!!! YEAH!! THANK YOU!!! Second, if you have not picked up a copy please get one on Amazon (the cheapest place to procure a copy) to support my beer fund!  For less than 20 bucks you get 512 pages of material on over 100 medical conditions and when not using this amazingly big book it also functions as a beer coaster or a potato chip or pizza plate holder when you’re watching the big game on TV (or for those in my kids generation – watching the big game on your computer or phone (because 20 years from now someone is going to read this column and ask “What is a TV”?). NOT BAD!

314) If you cannot tolerate your statin/cholesterol lowering drug or need to go to a lower dosage of a statin drug because of side effects then Zetia (ezetimibe) is NOW an option and it’s also being studied as an anti-prostate cancer drug! How groovy/awesome is that!

BREAKING NEWS!

(Reference: IMPROVE-IT Investigators. New England Journal of Medicine, published on June 3, 2015.)

BOTTOM LINE

LOWER IS BETTER! The combination of a statin drug with ezetimibe (also known as “Zetia”10 mg per day) resulted in a greater reduction of LDL (aka “bad cholesterol”) and reduced cardiovascular events greater than a statin alone. Side effects including muscle, gallbladder, and liver side effects and rates of cancer, over the course of the clinical trial, were the same in both groups (a good thing). It’s also being studied right now against prostate cancer but this is very preliminary.

WHAT ELSE DO I NEED TO KNOW?

Ezetimibe (Zetia) blocks the absorption of cholesterol from food/intestines and it’s a prescription drug. Someone can expect to get a 15-25% reduction in LDL with one pill of ezetimibe (not bad). However, here is the most recent, fabulous news!  JUST PUBLISHED clinical trial data (called “IMPROVE-IT”) with statins have actually found a moderate positive impact on clinical endpoints and not just cholesterol values with ezetimibe.  This should increase the use of ezetimibe immediately in those patients with problems taking statins or higher dosages of statins and reignite the discussion of a “lower is better” philosophy, because in high-risk patients ezetimibe and simvastatin lowered LDL to almost 53 mg/dl compared to approximately 70 mg/dl in simvastatin only participants. TELL ME MORE!!! (Okay, when you see all CAPS in texting it means you are YELLING – so I WILL STOP YELLING AND TELL YOU MORE!). The IMPROVE-IT trial was more specifically a double-blind, randomized trial of 18,144 patients from 1147 medical centers in 39 countries who had been hospitalized for an acute coronary syndrome (acute heart attack or high-risk unstable chest pain) within the previous 10 days. Th e combination of simvastatin (used to be known as Zocor-a statin drug) at 40 mg and ezetimibe (again Zetia) at 10 mg was compared to simvastatin (40 mg) by itself. The primary endpoint of this trial was the combined end point of cardiovascular death, nonfatal heart attack, unstable chest pain needing re-hospitalization, coronary revascularization (procedure like bypass or stent placed 30 or more days after randomized in the trial) or nonfatal stroke. The average age of the participants was 63-64 years of age (50 years or older to be eligible), 76% were male, 84% were Caucasian, 61% had hypertension, 27% had diabetes and 33% were current smokers! Additionally the mean BMI was 28, which is overweight, and the mean LDL was 84 mg/dl before they the trial started. YIKES!!! Apart from the fact that they already had a low LDL, these were not the healthiest group of boys and girls.  In fact, I was really disappointed that the researchers and the editorial in this New England Journal of Medicine article point out that this group as a whole was very unhealthy. And, apart from the higher smoking rate this group is actually reflective of the U.S. population! DOUBLE YIKES!!! Okay, back to our story boys and girls and dog (my dog Chauncey is watching me while I’m typing this article probably, wondering why PAACT has never given him a free official PAACT bone, squeeze toy or squirrel look alike)!

The median follow-up in this clinical trial was 6 years and the LDL cholesterol average at the end of the trial was 54 mg/ dl in the combination statin-ezetimibe group and 69.5 mg/d in the statin only group. The rate of the primary endpoint at 7 years was 32.7% in the combination group and 34.7% in the statin only group, which is only an absolute difference of 2 percentage points but this was still significant (p=0.02). Muscle, gallbladder, and liver side effects and cancer were similar between the two groups. Discontinuation of the medication in either group because of side effects was approximately 10-11% (again no difference). However, in reality compliance was a big issue throughout the trial because 42% of the participants in IMPROVE-IT (combination or statin alone group) stopped their study medication prematurely (for any reason), which is about 7% per year, which actually closely resembles what has been observed in other trials! In other words, it’s not the side effects that are causing patients to stop these drugs but the lack of compliance (boredom, forget, don’t like it, would rather be watching Tiger baseball or Michigan football, travels a lot… blah, blah, blah). I make fun of this but with lifesaving drugs or even supplements that help it is hard to find folks that will take pills almost all the time. So, this is why I always say that I love it when someone does not qualify for taking any pills because they are so healthy because pill taking is a PAIN IN THE GLUTEUS MAXIMUS (aka “buttocks” as Forest Gump used to say…and “Life is Like a box of chocolates – you never know what you are going to get unless of course you see the one in the box with nuts in it before you bite it then you know it is going to taste great!” Sorry I digressed!

BACK TO THE STORY….Adding ezetimibe lowered LDL by 24%. Keep in mind that no differences between the groups were found for death from cardiovascular disease or death from any cause (cancer…), but significant reductions were found in the combination group for the rates of heart attack and ischemic stroke [113]. This is a credible finding since the differences began to emerge after 1-year into the trial and it was only conducted for about 6 years (not a long time actually). Thus, overall it represents a moment where a non-statin therapy to reduce LDL can also reduce cardiovascular outcomes (something missing with niacin, and others). It appears that lower is better, and had these patients started with higher LDL levels arguably even better results would have been observed. It is also interesting that in the combination group the reduction in the inflammatory blood marker hs-CRP was also significantly reduced compared to the statin only group. This is part of the reason that I believe ezetimibe should continue to be studied against breast and prostate cancer marker.

Still, the IMPROVE-IT trial offers important new evidence for the “LDL Hypothesis” that lowering of this blood marker is the primary driver of what changes cardiovascular risk (after the first year of the study the LDL was 53 mg/dl in the combination group and 70 mg/dl in the statin only group. I know that there are many nice folk out there that want you to believe that cholesterol has nothing to do with heart disease and I think you know how I feel about that, which is similar to how I feel when Michigan State or Ohio State beats Michigan in any sport (it is just plain wrong).  Despite just a 2% difference in the primary endpoint in favor of the combination group, this is almost identical to what would have been predicted from past trials based on the LDL difference!

Again, offering more evidence for the LDL hypothesis. Ezetimibe was being studied by Harvard researchers in their laboratory, and they found preliminary evidence years ago that it may have some anti-prostate cancer effects. Regardless, this drug represents new options or hope for those that cannot achieve their target LDL with diet, exercise and statins. This also offers hope for new medications in the pipeline such as “PCSK9 inhibitors” that reduce LDL via reducing/blocking LDL receptor removal to allow for more LDL to be cleared from the circulation, and these agents have the ability to lower LDL (bad cholesterol) as much as 60%. ZOWIE BATMAN! However, the problem with these drugs is that they are supposed to be given by subcutaneous injection once every 2-4 weeks, and with overall compliance in the IMPROVE-IT trial not being very good, this is not a good sign of future drug compliance if PCSK9 blockers work. Personally, I don’t get excited about sticking myself with a needle every few weeks unless of course it helps me with my…you know what down there…. in my pelvic region! I mean my wallet or helps to make me more money! What were you thinking I was thinking???????!


315) Statins don’t work in women? Hmm really? 
BREAKING NEWS!(Reference: Wang A, Aragaki AK, Tang JY, Kurian AW, Manson JE, Chlebowski RT, et al. Statin use and all-cancer mortality: prospective results from the Women’s Health Initiative. J Clin Oncol 2015;33 (suppl; abstr 1506). & THE SUPPLEMENT HANDBOOK by Dr. MOYAD (Hey I know that dude he is the one that I love to love…okay I made that part up…but my new bestselling book is real.)

BOTTOM LINE

Interestingly, at the time of this chapter’s submission, data from the noteworthy Women’s Health Initiative (WHI) clinical trial was released at the annual American Society of Clinical Oncology (ASCO) meeting (again the largest cancer meeting and it is held in Chicago – the place with the big tower and beautiful winters). The study enrolled women aged 50-79 from 1993-1998 at 40 U.S. clinical centers. There were a total of 146,326 participants with a median follow-up of 14.6 years. A total of 23,067 incident cancers and 3,152 cancer deaths were observed. Numerous confounding variables were adjusted for, and compared with those that never used statins, those that did use statins had a significant 22% reduction in cancer mortality.  The reduction in cancer death was not associated with statin potency, duration or type of statin itself. Current statin use was associated with significantly reduced mortality of numerous cancer types, including breast, colorectal, ovarian, digestive, and bone/connective tissue cancer deaths. Interestingly, statin use was not associated with a decrease in cancer incidence despite its impact on mortality (THIS IS WHAT HAS ALSO BEEN OBSERVED IN PROSTATE CANCER BY THE WAY OR AS I LIKE TO TEXT “FYI”). The conclusion of the study was as follows: “In a cohort of postmenopausal women, regular use of statins or other lipid-lowering medications may decrease cancer mortality, regardless of the type, duration, or potency of statin medications used.” Thus, in the worst case scenario if cholesterol lowering does not alter the course of breast cancer and continues to only lower the risk of morbidity and mortality in women that is still a worst case scenario with ample merit don’t you agree? So, why wasn’t this headline news? Beats me! It doesn’t prove cause and effect but it’s one of the largest indirect looks ever conducted in women. Maybe the media was too obsessed with important stuff that day like whether or not Kim Kardashian was going to

–       STATIN PRIMARY PREVENTION TRIALS ONLY AND IMPACT ON WOMEN  (insert table here)

wear the blue or the black dress at a Hollywood party! COME ON PEOPLE WAKE UP! FYI – I think she should go with the black dress because like my wife she looks stunning in black and then for shoes I am thinking Jimmy Choo or Manolo Blahnik shoes which are actually on sale this week at Neiman Marcus…. sorry I digress again! Darn it!

STATIN PRIMARY PREVENTION TRIALS ONLY AND IMPACT ON WOMEN TRIAL

WHAT ELSE DO I NEED TO KNOW?

The leading cause of death in the U.S. for women and men is cardiovascular disease (CVD), and this has been the case for 116 of the last 117 years. CVD causes more deaths than cancer and chronic lower respiratory diseases (CLRD) combined. CVD causes 1 death per minute among females in the U.S. or over 400,000 deaths, which is approximately the same number of female lives lost by cancer, CLRD, and Alzheimer disease combined. The most recent U.S. statistics have recorded the following: approximately 41,000 deaths were from breast cancer, 70,500 female deaths from lung cancer, one in 30 deaths are from breast cancer whereas 1 in 7 was from coronary heart disease (CHD), and 1 in 4.5 females died of cancer and 1 in 3.1 died of CVD. CVD is also still a disease of the young and old. Approximately 150,000 Americans died of CVD last year who were less than 65 years of age and over one third of CVD deaths occurred before the age of 75 years (life expectancy is 78.7 years). The number 1 cause of death in women and men from age 65 and older is CVD (number 2 is cancer). Thus, it could be argued that the overall impact of lipid lowering with statins or lifestyle changes should be of paramount importance in women treated for breast cancer, concerned about prevention and a reduction in all-cause mortality.

BUT, DOC MOYAD I HEAR ALL THE TIME THAT STATINS HAVE NO EVIDENCE OF WORKING IN WOMEN! Well, that statement makes me as mad as at long-tailed cat stuck in a room full of rocking chairs or a mouse stuck in a room full of mouse traps or a hamster stuck in a room with a defective spinning wheel or….you get the idea! This is not accurate. Statins like any drug or supplement comes with benefits and catches and ideally I don’t want anyone taking any pills, but for the women (and men) that really need them it has changed lives so let’s review the trials with women that were healthy but at an increased risk of a cardiovascular events. Here we go…..Interestingly, in the AFCAPS/TexCAPS study, the effect of lovastatin on the risk of first major coronary event was greater in woman versus men (-46% vs -37%), but the number of women having such an event was small (20 out of 997), so there was no treatment difference between genders.  In the MEGA study, which used pravastatin, there was a 37% reduction in men versus 29% for women. Almost 70% of the participants in MEGA were women, but interestingly the average BMI was 23-24, which is far below what is observed in U.S. trials (BMI of 27-28) for men and women. In the JUPITER trial, which was stopped in 1.9 years because of its significant impact on reducing CVD events the average LDL reductions were 50% and high-sensitivity C-reactive protein (hs-CRP) was reduced by 37%. Positive impacts were observed in all subgroups evaluated and risk reduction in the rosuvastatin group was -46% for women and -42% for men. Women in JUPITER experienced a significant reduction in revascularization/unstable angina (-76%), and there was a non-significant reduction in nonfatal heart attacks (-44%) or heart disease death (-27%).  However, it needs to be reiterated that this trial was stopped in 1.9 years for already meeting its primary endpoint and other primary prevention trials also had short follow-up and smaller numbers of events. Thus, I find it striking in primary prevention that some “experts” make claims that the impact of statins in women is not known. A -76% in revascularization procedures means that these women were NOT getting BYPASS SURGERY or STENTS placed in their arteries and this is one thing that ALWAYS gets missed when talking about cholesterol lowering.  These medications have dramatically reduced the need for getting your chest cracked up and needing bypass surgery!  (SEE CHART ABOVE)

Statins, Safety and Type 2 Diabetes…THIS STUFF IS REAL!

In the appropriate individuals statins reduce all-cause mortality, cardiovascular events (especially costly cardiovascular procedures) and are of low cost (5 are now generic) and well tolerated overall. Regardless, the primary issue that still needs to be resolved is whether or not statins significantly increase the risk of diabetes, and if so is that risk negligible or relevant?  For example, it may be dose-related or primarily in those with diabetes risk factors. In the notable JUPITER trial there were 2.5 cardiovascular events or deaths avoided for each potential case of diabetes with rosuvastatin (Crestor). Thus, for most qualifying individuals the benefit appears to outweigh the risk, but more answers and clarity on this topic are desperately needed. The association of statins and type-2 diabetes is indeed a real finding from meta-analyses but causality has not been proven, but it appears women, the elderly and those on higher dosages may be at higher risk. Recent laboratory evidence suggests a potential mechanism of action whereby statins increase the risk of diabetes.  Investigators from McMaster University in Ontario, Canada have found that these drugs may activate an immune response pathway that hinders insulin signaling. Multiple statins activate NLRP3/caspase-1 inflammasome, a multiprotein complex (SAY WHAT?), which is known to encourage inflammation and insulin resistance. Interestingly, combining a statin with the drug glyburide (an inhibitor of NLRP3/caspase-1) suppressed these harmful effects in fat tissue of obese mice.  These negative effects of statins were also not found in mice genetically engineered to lack expression of NLRP3/caspase-1 inflammasome. WHAT ALL THIS SCIENTIFIC MUMBO JUMBO (Hey that was an elephant! Oops – his name was Dumbo) MEANS IS THAT NO ONE SHOULD TAKE A STATIN WITHOUT REALIZING THAT YOU WANT TO BE ON NO PILL OR THE LOWEST DOSE POSSIBLE BECAUSE HIGHER DOSES PROBABLY DO INCREASE THE RISK OF DIABETES IN SOME FOLKS!  Thus, especially in high-risk patients there may be value in monitoring insulin sensitivity during statin use and using anti-diabetes medications may even further reduce risk. Ultimately, if the overall risk of type 2 diabetes becomes consistently clinically significant researchers may find a way to improve this drug class or reduce diabetes risk with another pill, for example CoQ10 supplementation is also being investigated for this purpose.  Still, one mantra of this drug class (and others) NEEDS TO BE REPEATED… It appears more relevant than ever that DOCTORS need to encourage patients to be on the lowest dosage of a statin, along with moderate to aggressive lifestyle changes to maintain small dosage needs (or no drug). PATIENTS NEED TO TRY TO BE ON THE LOWEST DOSE OR NO DRUG…In fact, there is also recent data to suggest that consistent lifestyle changes such as exercise may provide similar benefits to these and other preventive medications at least in a secondary prevention setting. For example, a total of 4 exercises and 12 drug meta-analyses and the addition of 3 recent exercise trials were utilized in a recent investigation for a total of 305 randomized control trials with over 339,000 participants. A total of over 14,700 participants were randomized to exercise in 57 trials (Naci H, et al. BMJ 2013;347, published October 1, 2013). Four conditions with evidence on the impact of exercise on mortality outcomes were the focus: secondary prevention of coronary heart disease, rehabilitation of stroke, treatment of heart failure and the prevention of diabetes. No statistical differences were found between exercise and drug interventions in the secondary prevention of heart disease and pre-diabetes. Exercise was more effective compared to drug treatment among patients with stroke, and diuretics were more effective than exercise in heart failure. More studies are needed but current randomized data suggest the mortality benefits of exercise and prescription medications are similar in the secondary prevention of heart disease, rehabilitation after stroke, prevention of diabetes and even provide unique benefits in heart failure. It will be of enormous interest in the future to determine the impact of exercise on a variety of other diverse and similar medical conditions.

316) Statins and prostate cancer treatment. And the beat goes on….BREAKING NEWS AGAIN…JUST KEEP ON BREAKING…

(Reference: Harshman LC, J Clin Oncol 2015;33: Abstract 148 & Hamilton RJ, et al. J Clin Oncol 2015;33: Abstract 145.)

BOTTOM LINE

Recently, at ASCO (largest cancer meeting in the world, a large study from Harvard and Canada concluded with the following statement below (note: this does not prove cause and eff ect but

makes the lower cholesterol and statin theory against prostate cancer more interesting don’t you think? -“…statin use at the time of ADT initiation was associated with a significant increase in TTP on ADT even after adjusting for established prognostic factors.” (n=926 folks) Moyad comment – Patients appeared to have a better response to hormone therapy if they were also

taking a statin drug. -For ADT following primary or salvage radiation-“statin use was associated with improved overall and prostate cancer-specific survival and improved quality of life.” In terms of intermittent androgen deprivation (IAD)-“more off treatment intervals and longer off treatment.” (n=1364 folks studied) Moyad comment – Patients had a better response to IAD if they were on a statin drug.

WHAT ELSE DO I NEED TO KNOW?

I have nothing else to say except if men and women reduce their cholesterol while being treated for breast or prostate cancer and it doesn’t work in fighting cancer, then I apologize that all it might do is reduce the number 1 cause of death in men and women for 114 of the last 115 years. HEART HEALTHY = PROSTATE HEALTHY!!! (Moyad Trademark Circa 2003 in the medical literature and if you do not believe me look it up. So, if you use these terms at any point in your life you need to donate some money to PAACT and then donate some Money to the Moyad Beer fund, which is also known as MBF. T-shirts will be available soon!).

317) Metformin, breast cancer and a phase 3 trial! Why do I have to know about this? Please read on…AND TEACH ME ABOUT THIS DRUG and REMEMBER THAT EXERCISE AND DIET WORKED BETTER THAN THIS DRUG TO PREVENT TYPE 2 DIABETES (but you never get to hear about this!).

(Reference: Goodwin PJ, et al. Eff ect of metformin vs placebo on weight and metabolic factors in NCIC CTG MA.32. J Natl Cancer Inst 2015;107: epub ahead of print. & Diabetes Prevention Program or DPP in New England Journal of Medicine 2002.)

BOTTOM LINE

Metformin (generic “natural” drug derived from the French Lilac”) given to non-diabetic women in the hope of preventing breast cancer from returning at least appeared to make participants more heart healthy! So, should patients ask their doctors about it in order to lose a little weight, drop their blood sugar and prevent type II diabetes if they are at higher risk? Yes, but remember that exercise and weight loss via diet arguably worked better in preventing type 2 diabetes.

WHAT ELSE DO I NEED TO KNOW?

(THIS IS A LONG ARTICLE SO BUCKLE UP…IT’S INTERESING, BUT IT’S ABOUT AS LONG-WINDED AS My grandfather when he talks about the positives and negatives of his colon health and latest bowel movements just as I am about to take the first bite of my pizza…sorry Grandpa I suddenly lost my appetite!) Metformin has actually been available in Europe since the 1950s but was not approved by the U.S. FDA until December 30, 1994.  An extended release (XR metformin) version was approved in October 2000. Metformin was actually first synthesized and found to lower blood sugar in rabbits in the 1920s and then put aside for decades because of an increase in insulin synthesizing/utilization research. A 1957 published clinical trial of diabetes (by French physician Jean Sterne – who coined the name of metformin as the glucose eater or “Glucophage”…REMEMBER THIS DRUG NAME) was then completed and the U.K introduced it in 1958 and Canada in 1972. Metformin is now considered a first-line drug treatment along with diet and exercise for adult and pediatric patients with type 2 mellitus because of its favorable overall profile (glucose control, weight loss and low risk of hypoglycemia). It is arguably the only drug proven to prevent pre-diabetes (high-risk diabetes patients) from becoming diabetes and is a primary treatment in patients with metabolic syndrome. Overall, few drugs in medicine cost less with such a long-term safety profile and even added potential heart health benefits. WOW and WOW SPELLED BACKWARDS!!  Metformin works by reducing liver glucose production (“inhibiting gluconeogenesis”) and increasing skeletal muscle tissue uptake of glucose. Metformin essentially leads to a maximum 75% reduction in liver glucose production. It also reduces blood insulin levels (not directly), increases insulin sensitivity, suppresses synthesis of proteins, fatty acids and cholesterol, and increases the utilization of free fatty acids.  Metformin has also demonstrated some evidence of reduced intestinal glucose absorption. Metformin increases insulin sensitivity by activating hepatic and muscle AMP-activated protein kinase (AMPK – “metabolic master switch”), which results in reduction of fatty acid synthesis and stimulation of fatty acid oxidation in the liver and increase in muscle glucose absorption.  BLAH! BLAH! BLAH!  Metformin is generally available in 500, 850, and 1000 mg tablets. The starting dose is 500 mg twice a day or 850 once a day, given with meals. The most common dosage utilized in the Diabetes Prevention Program (DPP) was 850 mg twice a day. In general, clinical experience suggests 500 mg once a day with a meal and increasing dose in 500 mg increments every 2-4 weeks until maximum dosage is achieved. Metformin XR can be prohibitively expensive and available in 500- and 750-mg tablets utilized with the evening meal.  The half-life of metformin is on average 5-6-hours in plasma (longer retention in red blood cells or blood-up to 18 hours), which suggests 94% of the drug is removed by the body in 24 hours. This short half-life emphasizes the need for daily compliance whether it is for patients or when measuring glucose and other parameters in clinical trials.  Metformin is limited by gastrointestinal complications (soft stool, diarrhea, gas, abdominal pain and more rarely nausea and vomiting) in up to 50% of patients, but these adverse effects are usually transient and resolve within days to weeks of initiating treatment. Additionally, gastrointestinal side effects are reduced greatly by again, titrating increasing dosages of the drug every 2-4 weeks (for example 500 or 850 once a day for 2 weeks and then 500 mg additional) and when it is consumed with food.  Although food has been reported to reduce the rate and extent of metformin absorption by increasing the time to peak plasma concentration by approximately 40 minutes, but this appears to be a small issue especially compared to the overall importance of long-term compliance. Less than 5% of patients in clinical trials are not able to tolerate the drug due to side effects. Extended release (XR) metformin appears to improve gastrointestinal tolerability and can be given once a day, but is more expensive (no thanks!).  Metformin can reduce vitamin B12 and/or potentially magnesium levels, so these values should be monitored by the doctor that you adore or love the most in your life (not a romantic love but a “hey let me buy you a cold beer” kind of love). It has been known that this drug interferes with B12 absorption in the last part of the small intestine and can lower B12 in 10-30% of patients. The reduction of B12 by metformin appears to be dose-dependent.  Rarely, patients complain of a “metallic taste” with the drug, which has been more commonly found with similar medications.  Regardless, “metallic taste” has been reported in clinical trials in approximately 3 to 11% of patients. It also appears to be self-limiting with only 0.5% of patients complaining of metallic taste after 3 months of treatment. Regardless, a reduction in dose or the passing of time appears to resolve this issue almost immediately in patients distressed by this issue.  The most serious concerning adverse event with metformin is lactic acidosis, where a low pH in body tissues and blood (acidosis) along with increases in lactate is problematic. The overall incidence of lactic acidosis on metformin has been estimated to be less than 1 case per 1000 total patient years on the drug. In other words, it has become as rare as almost any other drug especially when working closer with your doctor.  Still, metformin is contraindicated in some individuals because of impaired kidney function and the potential concerns of lactic acidosis (many doctors think this is overrated and metformin should be available over the counter, but that’s not going to happen. You should talk to your doc about these things and not a newsletter with a guy that likes to make funny jokes a lot for personal therapy who also happens to be a doctor).  Iodinated contrast media administration given for some imaging tests could result in lactic acidosis in a patient utilizing metformin. However, this rare adverse effect occurs if the contrast causes renal failure. Metformin is excreted primarily by the kidneys so continued utilization of metformin after the initiation of kidney failure causes toxic concentrations of the drug and subsequent lactic acidosis. In order to avoid this complication metformin should be withheld after the administration of contrast agent for 48 hours, and if renal function is normal after 48 hours from receiving contrast then metformin can be reinitiated. However, despite what the package insert recommends, which is also to withhold metformin 48 hours before contrast medium is given, others have argued there is no justification for this before and then after procedure (for 48 hours). Still, it seems prudent to stop metformin two days before and after contrast in any person with a hint of kidney issues simply because the benefit exceeds the risk in my opinion THE TRIAL THAT SHOCKED THE WORLD (DPP = Diabetes Prevention Program)!!!

This landmark trial was published on February 7, 2002 in the New England Journal of Medicine. This trial consisted of 3234 non-diabetic individuals with elevated fasting blood glucose (mean of 106 mg/dl and hemoglobin A1c of 5.9% and 67% with a fasting glucose of 95-109 mg/dl and 33% with 110-125 mg/dl) were assigned to placebo, 850 mg metformin twice daily (850 mg for first month then 850 mg twice a day thereafter) or lifestyle changes with a goal of at least 7% weight loss (via low-fat low caloric diet) with 150 minutes of physical activity per week. Mean age and BMI was 51 years and 34, respectively, with 68% women, 45% members of a minority group and 20% 60 years of age or older. However, almost 33% of the participants had a baseline BMI of 22 to 29! Approximately 70% of the participants had a family history of diabetes and 16% of the women had a history of gestational diabetes. The average follow-up was only 2.8 years and compared to placebo the group utilizing metformin reduced the risk of diabetes by 31% (95% CI 17- 43) and the lifestyle intervention reduced the incidence by 58%. (LIFESTYLE CHANGES BEAT ONE OF THE BEST SELLING DRUGS OF ALL TIME…EXTRA, EXTRA, READ ALL ABOUT IT IN THE PAACT NEWSLETTER).  In addition, one of the key findings of this landmark publication was the “lifestyle intervention was significantly more effective than metformin.” In fact, the number needed to treat (NNT) or to prevent one-case of diabetes over 3-years for metformin was 13.9 persons for metformin and 6.9 for lifestyle-intervention.  Regardless of BMI group (22-<30, 30-35 or >35) metformin or lifestyle was beneficial in reducing the incidence of diabetes regardless of gender and race or ethnic group, but metformin appeared to have a greater impact in those with a BMI of 35 or more. Overall, treatment effects did not significantly differ by gender or race or ethnic group. Daily caloric intake was reduced by 249 kcal in the placebo group, 296 in the metformin group, and 450 kcal in the lifestyle group (p<0.001). The average weight loss was 0.1, 2.1 (4.6 pounds), and 5.6 kg (OVER 12.3 POUNDS) in the placebo, metformin, and lifestyle groups (p<0.001). Interestingly, side effects with metformin were significantly (p<0.02) greater than placebo in terms of gastrointestinal symptoms (diarrhea, flatulence, nausea, and vomiting), but were significantly (p<0.02) lower with lifestyle changes compared to placebo!!!!!! YEAH BABY!!! LIFESTYLE RULES!!!   Anti-Cancer!? Now, perhaps, the most observed and truly landmark event is a phase 3 trial being conducted in North America, the United Kingdom, and Switzerland and it has already completed enrollment of 3649 non-diabetic women receiving conventional treatment for T1-3, N0-3, M0 breast cancer diagnosed during the previous 12 months. Interestingly, patients needed to have a fasting glucose of less than or equal to 126 mg/dl (7.0 mmol/L), which is the threshold for diabetes diagnosis, but essentially enrolls only pre diabetics or those with normal blood sugar. Women with a history of lactic acidosis, current use of diabetes drugs, previous or recurrent breast cancer, greater than moderate intake of alcohol or “marked” liver, kidney, or cardiac abnormalities were excluded. Subjects were randomized to metformin 850 mg oral caplet twice a day for 5 years, which included a 4-week initial metformin acclimatization period of 850 mg a day for 4 weeks and then the addition of another 850 mg per day.  Interestingly, this study also included a metabolic substudy that has been completed!!! AND YOU ARE ABOUT TO GET THE BREAKING NEWS RESULTS!!! Th e first 492 individuals with fasting blood samples at baseline and after 6-months were included. Mean age, BMI, and glucose of participants in the substudy was 52 years, 27-28, and 95 mg/d or 5.3 mmol/L (range 88-101 mg/dl or 4.9-5.6 mmol/L), respectively. The results from this substudy were impressivem because the results below “did not vary by baseline BMI or fasting insulin” including the following:

• Weight reduced 1.7 kg (3.7 pounds) or -2.3% with metformin and increased 0.5 kg or +0.7% with placebo (p<0.001). BMI change vs placebo also was significant (p<0.001).

• Glucose reduced 1.9% with metformin and increased 1.9% with placebo (p=0.002).

• Insulin reduced 11.1% with metformin and did not change with placebo (p=0.002)

• hs-CRP was unchanged with metformin and increased 6.7% with placebo (p=0.002).

• Leptin (hormone that when it goes down is a symbol that the drug has positive/beneficial metabolic changes…

GOOD NEWS!!!) reduced 9.5% with metformin and increased 10.7% with placebo (p<0.001).   Interestingly, members of this research group had found previously that higher insulin levels in breast cancer were associated with two times the risk of distant recurrence and three times the risk of death.

318) Adult vaccines may reduce your risk of a heart attack and have anti-cancer eff ects? Has Moyad lost it? (well yes, I never had “it” but I do believe this preliminary research!). VACCINES = HEART HEALTHY!!!  (References:  1. Corrales-Medina VF, et al. JAMA 2015;313:264-274.  2. Mitchell DA, et al. Nature March 19 2015.).

BOTTOM LINE

If you qualify for any adult vaccine right now, please go get it because it may not only reduce your risk of cardiovascular disease (CVD) but it might also enhance the effects of your cancer treatment. This is preliminary research but who caresthis is a SIDE BENEFIT (get it….not a side effect) of some of these adult vaccines.

WHAT ELSE DO I NEED TO KNOW?

Vaccines are no longer helpful just for kids, they are incredibly helpful for adults! Adult men and women need to be more vigilant about getting them. People will not hesitate to take an unproven supplement to boost or support the immune system but they are probably not aware that there are vaccines that do a much better job of doing this than any other over the counter pill.

I have explained in the past how many adult vaccines like the fl u vaccine are heart-healthy and you need to get these vaccines for all the side benefits! And now comes the latest research that preventing pneumonia might fight heart disease and other vaccines could enhance the effects of cancer treatment! Okay, this is preliminary stuff but it’s quite groovy, cool, and hip! A recent study of over 5800 adults found that pneumonia might be an independent risk factor for cardiovascular disease (CVD)! Hospitalization for pneumonia was associated with an increased short- and long-term risk of CVD! Why? Infections can cause proinflammatory changes in the composition of heart disease plaques and make them more vulnerable to causing sudden cardiac events (heart attack, stroke…). And, in other research it seems when someone suff ers from a serious infection like pneumonia and recovers, the inflammation in the body continues for arguably months and months after the time the person has recovered. So, you feel better but the body is still dealing with all the effects of the infection. Not nice!  Additionally, in a somewhat stunning recent small randomized human study with brain tumors researchers gave a small number of individuals a tetanus/Td shot (actually tetanus/ diphtheria toxoid) to enhance their immune response to an experimental dendritic cell immune therapy and for some of the patients it did appear to provide a “boost” or enhanced treatment effect! In fact, it appeared to significantly enhance survival in patients with glioblastoma. Among the 6 patients that received the Td shot, three lived between 20 and 24 months from diagnosis, and three lived longer than 3 years – including one patient that is still alive after 9 years. And, this data compares with a median survival of 18.5 months in the control group of this study. Researchers thought the Td shot would work by causing an immune response locally at the vaccine site but were surprised that it actually appeared to cause a systemic (body wide effect) immune response. This is only a small human study of brain cancer. However, I do think it is time to get excited about getting both pneumonia vaccines if you qualify. PCV13=Prevnar and PPSV23=Pneumovax since September 2014 are now both recommended just not at the same time, so talk to your doctor because if you are 65 years or older or in many other special circumstances you may qualify ASAP. Also, for all those adults that have let too much time go by since they had their tetanus shot or never had one – it is time to go in there and get it ASAP if you qualify!

319) Ginseng looks good again to battle cancer-related fatigue (CRF)!! This is really getting interesting! And, it should be an option now because many of the new drugs work very well, but fatigue is a big problem in some patients (for example with Xtandi, chemotherapy, hormone suppression or listening to your kid tell you the many reasons why they could not clean up there room over the past month – that is also exhausting after a while). BREAKING NEWS! YEAH!!!

(Reference: Yennurajalingam S, et al. Integrative Cancer Therapies 2015; and Barton DL, J Natl Cancer Inst 2013;105:1230-1238 and Moyad MA. Th e Supplement Handbook, 2014.)

BOTTOM LINE

If you are experiencing fatigue from cancer treatment or just trying to prevent it then 1000-2000 mg American ginseng (3- 5% ginsenosides) is a good option and/or 800 mg per day of Panax ginseng (Asian ginseng at 7% or more ginsenosides) may also soon be a good option. This research was done at two places you may never have heard of – Mayo Clinic and MD Anderson Cancer Center (sarcasm alert #546). Look at Ginseng Board of Wisconsin web site for the low cost brand that was tested in the Mayo clinic trial (www.ginsengboard.com). Also, several clinical trials of weight lift ing or resistance exercise just 2-3 times a week also reduces CRF.

WHAT ELSE DO I NEED TO KNOW?

It was already time to make ginseng an option for cancer related fatigue in 2013 when the Mayo clinic and 40 other medical centers completed the results of an 8-week study of American ginseng 2000 mg per day versus placebo to reduce fatigue and it worked! They used a ginseng from the Ginseng Board of Wisconsin (www.ginsengboard.com) so this is the one I recommend! The one from the big clinical trial is the one you can trust. The reason this needs to be an option soon is simply due to the LACK OF OPTIONS FOR CANCERRELATED FATIGUE (CRF) THAT ARE SAFE. How bad is CRF?! In clinical studies it can range as high as 60-90% and it’s also a limiting factor of one of the best prostate cancer drugs ever invented known as “Xtandi.” In this new MD Anderson Cancer Center study 30 patients with CRF (rated as 4 or more out of 10 on a scale) ingested 800 mg a day of Panax ginseng (Asian ginseng prepared from the root with 7% or more ginsenosides – the active ingredient) for 29 days. Median age of patients was 58 years and capsules were provided by Indena S.p.A. (Milan, Italy).  It’s also interesting that 10 of the patients were being treated for genitourinary cancers. Feelings of well-being and score for appetite significantly improved as well as fatigue on ginseng. The median improvement was a nice 5 points on a scale! This is outstanding, but keep in mind that this is preliminary but past research really supports that this is a real impact! Th e results of this small study not only show efficacy that the product was safe and no side effects were associated with the supplement. It also suggests that again not just fatigue but appetite, quality of life and pain improved over 4 weeks. A total of 63% of the patients noted moderate to vast improvement in their CRF with ginseng treatment.  Ginseng appears to be impacting or reducing the effects of pro-inflammatory compounds via some mechanism that is being studied now at Mayo Clinic and many other centers. Ultimately the study concluded in the following way “We conclude that high-dose Panax Ginseng is safe and tolerable and rapidly improves CRF. Our findings also suggest that PG can improve symptoms such as pain, appetite, sleep disturbances, and overall Quality of Life. Randomized, placebo-controlled trials of Panax Ginseng are justified.” BEAUTIFUL SENTENCE DON’T YOU THINK?! (of course it is!).  THAT’S ALL FOLKS…. See you in FALL, when I will write about many other serious issues and give timeless advice in the next newsletter, such as why it is never good to wait more than 1.214 seconds to say “ABSOLUTELY NOT” if your spouse asks you if he or she “looks fat in this new summer outfit?”  And why it is never smart to drink 5 glasses of water before renewing your driver’s license at the DMV with the no on-site bathroom (you are number 103 and they just called number 12 and now it is decision time folks).