I think most of us can agree that we want to age as gracefully as possible. But, what does this mean? While we may want to avoid physical ailments, such as achy joints and musculoskeletal pain, cognitive decline seems to be one of the scarier prospects as we age. The one organ in our body that we can’t yet transplant is the brain, so we really need to keep it in the best shape possible. We will all experience some form of age-related cognitive decline. But what about more significant changes in brain function?

The prevalence of mild cognitive impairment is hard to quantify, but roughly 16 to 22 percent of us will experience it (1). The reason for the range is that it is difficult to define but is thought of as a disorder that is between normal cognition and dementia. However, it is not a normal stage of aging. Mild cognitive impairment may lead to dementia, which is defined as affecting the memory and also at least one other part of the brain, such as executive functioning (2). The most common form is Alzheimer’s disease.

Who is at highest risk for decline from mild cognitive impairment and dementia? It turns out that this is a potential question of gender. Of those with mild cognitive impairment, women tend to worsen at an almost two times faster rate than men (3). However, researchers were baffled as to why.

There are preventions and treatments that may alter these different disorders that affect our mental functioning.

There may also be tests to determine whether you are at increased risk for dementia. These range from a short mental exam in the physician’s office to a saliva test that measures cortisol levels, the stress hormone. Higher levels of cortisol at night than normal were associated with significantly less brain volume and reductions in cognitive function in participants who did not have signs of impairment yet (4).

As “location, location, location” is important to real estate, it seems that lifestyle modifications including exercise, diet and overall brain fitness may be important to cognitive functioning.

Where do drugs fit in terms of treating dementia? The main class of drugs, cholinesterase inhibitors, seems to disappoint and also appears to have significant side effects.

Let’s look at the evidence.

Side effects of medication

Unfortunately, we do not have medication that is a silver bullet to successful outcomes in dementia. The mainstay medications are among a class referred to as anti-cholinesterase inhibitors, drugs that have a mild effect on dementia. These drugs include Aricept (donepezil), Exelon (rivastigmine) and Razadyne (galantamine). In a recent study, results showed that anti-cholinesterase inhibitors caused significant weight loss (5). Compared to those not on anti-cholinesterase inhibitors, there was a 23 percent increased risk of at least 10 pounds or more in unintentional weight loss over 12 months. There were more than 6,000 patients who were 65 years and older involved in the VA health systems retrospective study. This means that approximately 1 in 21 patients treated with these drugs may experience harmful weight loss over one year. Talk to your doctor about the risks and benefits of this drug class.

Exercise, exercise, exercise

Why? There are three recent studies showing exercise’s beneficial impact on cognitive functioning. Exercise may play a role in not just prevention but also in treatment.

Two of the studies were presented at the Alzheimer’s Association International Conference. In one, results show that exercise actually reduced tau proteins in patients over the age of 70 with prediabetes and amnestic mild cognitive impairment (6). These are patients considered at very high risk for Alzheimer’s disease.

The patients who saw a benefit did moderate to high intensity aerobic exercise compared to those who did stretching. The key to success in patients who are older (55 to 89 years) was to gradually increase the intensity and duration of exercise over a six-week period until 30 out of 45 minutes were spent at 75 to 85 percent of their maximum heart rate. The frequency of exercise was four days a week. The exercise increased blood flow to areas of the brain typically affected by Alzheimer’s disease.

In another study, results show that walking 40 minutes in addition to warm-up and cool-down periods, totaling one hour of exercise three times a week, could improve cognition in those with vascular cognitive impairment (VCI), another form of dementia (7). This population was composed of 56- to 96-year-olds with mild VCI. The duration of the study was six months.

A third exercise study was a randomized controlled trial (RCT), the gold standard of studies. In this study, participants trained to moderate to intensive aerobic exercise levels, 70 to 80 percent of maximum heart rate (8). The subgroup population that maintained at least an 80 percent adherence to the exercise regimen saw a significant positive change in the Symbol Digit Modalities Test (SDMT), a test used for attention and mental speed, compared to the control. However, the primary end point did not reach statistical significance. There was also an improvement in neuropsychiatric symptoms in the treatment group. These patients trained over a four-month period and had mild to moderate Alzheimer’s disease at baseline. This is the first study to indicate that exercise could have an impact on those with Alzheimer’s disease. The median age was 72 for the treatment group.

The role of diet

In a study, those who had the greatest adherence (top tertile) to the MIND diet were cognitively 7.5 years younger compared to those who had the least adherence (bottom tertile) (9). The MIND diet is a modified combination of the Mediterranean diet and the dietary approach to stop hypertension (DASH) diet. This was a prospective (forward-looking) observational study over a 4.7-year period involving almost 1,000 patients with a mean age of 81 years.

Lifestyle modifications

So far, we have seen the potential benefits of diet and exercise as separate entities. But what if we brought numerous components of lifestyle modifications together? In the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) study, results show that a multidisciplinary approach to lifestyle modifications potentially slowed cognitive decline in a healthy older population (10). The treatment arm participants had a 25 percent improvement in cognitive scores, compared to the control group given health advice only. The lifestyle modifications in the treatment arm included diet, exercise, brain training and management of vascular risk factors. This was a large, 1,260-participant, RCT involving 60- to 70-year-olds over a two-year duration. The population, though healthy, was at risk for mild cognitive impairment.

Testing for risk

In a study involving the Memory Binding Test (MBT), those who did not perform well were at a significantly greater risk of amnestic mild cognitive impairment and dementia (11). This is a test that can be performed in a physician’s office in about 10 minutes. The test involves associative binding between two word lists. Those who do poorly on the test are at 2.5 times increased risk of amnestic mild cognitive impairment and at a greater risk of dementia. The test had good durability with up to a decade of follow-up.

Thus, lifestyle modifications, with or without medications may have powerful effects in preventing and potentially treating mild cognitive decline and dementia.

References:

(1) Lancet. 1997;349(9068):1793; Ann Intern Med. 2008;148(6):427. (2) uptodate.com. (3) AAIC 2015. Posters P4-108. (4) Neurology. Online 2015 Aug 19. (5) J Am Geriatr Soc. 2015;63(8):1512-1518. (6) AAIC 2015. Oral presentations 0504-05. (7) AAIC 2015. Oral presentations 05-04-04. (8) EAN 2015. Abstract O310. (9) Alzheimers Dement. 2015 Jun 15. (10) Lancet. 2015 Jun 6;385(9984):2255-2263. (11) AAIC 2015. Abstract O3-10-04.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com or consult your personal physician.

Millions of Americans take herbal supplements. In fact, a survey from 2007 showed that 18 percent of Americans used herbal supplements in the previous year (1). Many take them on a daily basis, hoping they will prevent disease, keep them healthy, or even help treat disease, with or without conventional drugs. Many think that herbal supplements, unlike most medications, are natural substances, and therefore are likely to be safe.

Herbs have been used for thousands of years. Hippocrates, the father of medicine, recognized that there may be potential benefits of taking St. John’s wort for the treatment of mood disturbances. Another substance, saw palmetto, was used by the Egyptians for urinary tract problems in the 15th century B.C. (2).

However, even with a long tradition, are they really safe and effective? Even more, are we getting what the label says is in the bottle? Earlier this year, the NYS Attorney General performed DNA tests on 78 bottles of herbal supplements at Target, GNC, Walmart and Walgreens. Eighty percent did not contain the labeled ingredients, and some contained high levels of mercury, arsenic and lead (3). They also contained some substances that patients may be allergic to when the label on the bottle claimed otherwise.

The problem lies with the fact that herbal supplements are self-regulated. Manufacturers must label them with a disclaimer, saying that the content and health claims have not been reviewed by the FDA and that they are not meant to treat or prevent disease. Would you be comfortable buying drugs that were self-regulated? Probably not!

Many think the worst thing that could happen is they don’t help. Unfortunately, this may not be the worst effect. They may or may not work – the research on most is not very compelling. They also may be harmful on several levels: some cause interactions with drugs, such as Coumadin; some are incorrectly labeled regarding contents or doses; some include unlabeled medications in the bottles; and some cause side-effects. Just because they are said to be natural, doesn’t mean they’re safe.

Let’s look at the evidence.

Content of herbal supplements

We want to be certain that the contents in the bottle match what is on the label. Unfortunately, the recent investigation isn’t the first time the issue has been raised. An earlier study found that not all herbal supplements contain what is claimed, and some contain potentially harmful contaminants or inaccurate concentrations. Canadian researchers tested 44 herbal supplements from a dozen companies in the U.S. and Canada (4). They found that only 48 percent contained the herb that was on the label. In addition, about one-third of these supplements also contained fillers or contaminants. For example, a bottle labeled St. John’s wort actually contained a laxative from a plant called Alexandrian senna, and no St. John’s wort. With two other popular herbs, ginkgo biloba, used for memory, and echinacea, used to treat or prevent colds, there were fillers and potentially harmful contaminants in the bottles. These were identified using a sensitive DNA testing technique called DNA barcoding.

Black Cohosh

Black cohosh is used by women to help treat vasomotor symptoms, specifically, hot flashes associated with menopause. In a local study done at Stony Brook University Medical Center, as many as 25 percent of the bottles tested did not contain black cohosh (5). They tested 36 bottles acquired from brick-and-mortar chain stores and online. David Baker, M.D., an Obstetrics/Gynecology professor, also utilized the DNA barcoding technique mentioned above.

Ginkgo Biloba

Does ginkgo biloba live up to its claim of helping improve memory or prevent dementia? Unfortunately, in the first, large, double-blinded, randomized controlled trials (RCT), the gold standard of trials, results were disappointing (6). Ginkgo biloba was no better in preventing dementia or Alzheimer’s disease than a placebo. There were more than 3,000 participants in the trial; most did not have cognitive issues, but 14 percent had mild cognitive impairment. The treatment group took 120 mg of ginkgo biloba.

This is only one, albeit large, well-designed, study. But at least this supplement is safe, right? Well, in a toxicology study using lab animals, results demonstrated an increased risk of developing cancer, especially thyroid and liver cancers, as well as nasal tumors (7). Researchers point out that, while this is an interesting finding, it does not mean necessarily that the results are transferable to humans. Also, the doses used in this toxicology study were much higher, when compared to those taken by humans.

Red yeast rice and Phytosterols

Lest you think that herbs are not effective, red yeast rice is an herbal supplement that may be valuable for treating patients with elevated levels of cholesterol. In a study in patients with high cholesterol who refused or had painful muscle side effects from statin treatment, results showed that red yeast rice and lifestyle changes were effective in lowering LDL “bad cholesterol” levels (8). Patients making lifestyle changes alone were able to lose weight and maintain lower LDL levels over one year. The patients taking red yeast rice maintained LDL reductions over the year, as well. When phytosterols were added for patients taking red yeast rice, there was no further improvement in cholesterol levels. Again, some herbs may be effective, while others may not.

Resources

By no means are all herbs suspect, but you need to perform some due diligence. What can be done to make sure that doctors and their patients are more confident that the herbal supplements contain what we think? Well the best would be if an agency like the FDA would oversee these products. However, since that has not happened yet, there are resources available. These include Consumer Labs (www.Consumerlabs.com), Center for Science in the Public Interest (www.CSPInet.org), and NIH National Center for Complementary and Alternative Medicine Herb Fact Sheets (www.nccam.nih.gov/health/herbsataglance.htm), and Natural Medicines Comprehensive Database (www.naturaldatabase.com).

Conclusion

When taking herbal supplements, it is very important that patients share this information, including the brand names and doses, with their doctors and pharmacists. Herbal supplements may interact with medications, but they also may not contain labeled ingredients, and could have detrimental effects. If you have symptoms that are not going away, it could be due to these supplements. The best natural approach is always lifestyle modification.

Herbal supplements are sorely lacking proper regulation. So caveat emptor — buyer beware when it comes to taking herbal supplements.

References:

(1) Natl Health Stat Report. 2008. (2) JAMA. 1998;280(18):1604. (3) NYTimes.com. (4) BMC Medicine 2013, 11:222. (5) J AOAC Int. 2012 Jul-Aug;95(4):1023-34. (6) JAMA 2008;300:2253. (7) ntp.niehs.nih.gov. (8) Am Heart J. 2013;166(1):187-196.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com or consult your personal physician.

There is some thought that obesity may be reaching a plateau. Is this true? It depends on how the data is analyzed. According to one recent study, yes; it is plateaued when looking at short, two-year periods from 2003 to 2011 (1).

However, another, more recently published, study shows a picture that is not as positive (2). The study’s authors believe obesity has not plateaued; when looking over a longer period of time, statistics say that obesity has reached a new milestone.

There are now more obese patients in the United States, 67.6 million, compared to those who are overweight, 65.2 million. This is based on a study that reviewed data from the National Health and Nutrition Examination Survey (NHANES). These results were in adults over the age of 25. This should be an eye-opener. In fact, the researchers go even further to estimate that from the 1988-1994 survey to the 2007-2012 survey NHANES data show that 8 percent more women and 12 percent more men became overweight or obese.

Unfortunately, according to one study, the probability is not very good for someone to go from obese to “normal” weight in terms of body mass index (3). In this observational trial, results show that an obese man has a 0.5 percent chance of achieving normal weight, while a woman has a slightly better chance, 1 percent. This study used data from the UK Clinical Practice Datalink. The data were still not great for men and women trying to achieve at least 5 percent weight loss, but better than the prior data. Patients who were more obese actually had an easier time losing 5 percent of their body weight.

What are two major problems with being obese? One, obesity is a disease in and of itself, as noted by the American Medical Association in 2013 (4). Two, obesity is associated with — and is even potentially a significant contributor to — many chronic diseases such as cardiovascular disease (heart disease and stroke), high blood pressure, high cholesterol, atrial fibrillation, diabetes, cancer, cognitive decline and dementia. When I attended the 28th Blackburn Course in Obesity Medicine in June 2015 at Harvard Medical School, a panel of experts noted that there are over 180 chronic diseases associated with obesity. In this article, we will focus on one significant multifaceted disease, cancer.

Watch out for cancer

One of the more unpredictable diseases to treat is cancer. What are the risk factors? Beyond family history, and personal history, obesity seems to be important. In fact, obesity may be a direct contributor to 4 percent of cancer in men and 7 percent of cancer in women (5). This translates into 84,000 cases per year (6). On top of these stunning statistics, there is about a 50 percent increased risk of death associated with cancer patients who are obese compared to those with normal BMIs (7).

What about with breast cancer?

The story may be surprising and disappointing. According to an analysis of the Women’s Health Initiative, those who were obese had increased risks of invasive breast cancer and of death once the diagnosis was made (8). The severity of the breast cancer and its complications were directly related to the severity of the obesity. There was a 58 percent increased risk of advanced breast cancer in those with a BMI of greater than 35 kg/m2 versus those with normal BMI of <25 kg/m2. And this obese group also had a strong association with estrogen-receptor-positive breast cancer.

However, those who lost weight did not reduce their risk of breast cancer during the study. There were 67,000 postmenopausal women between the ages of 50 and 79 involved in this prospective (forward-looking) study. The researchers do not know why patients who lost weight did not reduce their risk profile for cancer and suggest the need for further studies. This does not imply that lifestyle changes do not have beneficial impact on breast cancer.

Why might this be the case with cancer and obesity?

We find that fat is not an inert or static substance, far from it. Fat contains adipokines, cell-signaling (communicating) proteins that ultimately may release inflammatory factors in those who have excessive fat. Inflammation increases the risk of tumor development and growth (9).

What can we do?

There is a potentially simple step that obese cancer patients may be able to take — the addition of vitamin D. In a recent study in older overweight women, those who lost weight and received vitamin D supplementation were more likely to reduce inflammatory factor IL-6 than those who had weight loss without supplementation (10). This was only the case if the women were vitamin D insufficient. This means blood levels were between 10 and 32 ng/mL to receive vitamin D.

Interestingly, it has been suggested that overweight patients are more likely to have low levels of vitamin D, since it gets sequestered in the fat cells and, thus, may reduce its bioavailability. Weight loss helps reduce inflammation, but the authors also surmise that it may also help release sequestered vitamin D. The duration of this randomized controlled trial, the gold standard of studies, was one year, involving 218 postmenopausal women with a mean age of 59. All of the women were placed on lifestyle modifications involving diet and exercise. The treatment group received 2,000 IU of vitamin D3 daily. Those women who received vitamin D3 and lost 5 to 10 percent of body weight reduced their inflammation more than those in the vitamin D group who did not lose weight.

What does medicine have to offer?

There are a host of options ranging from lifestyle modifications to medications to medical devices to bariatric surgery. Recently, the FDA approved two medical devices that are intragastric (stomach) balloons (11). The balloons are filled with 500 mL of saline after inserting them in the stomach via upper endoscopy. They need to be removed after six months, but they give the sense of being satiated more easily and help with weight loss. One, the ReShape Dual Balloon, is intended to go hand-in-hand with diet and exercise. It is meant for obese patients with a BMI of 30-40 kg/m2 and a comorbidity, such as diabetes, who have failed to lose weight through diet and exercise. In a randomized controlled trial involving 326 obese patients, those who received the balloon insertion lost an average of 14.3 lb in six months, compared 7.2 lb for those who underwent a sham operation.

Lifestyle modifications

In an ode to lifestyle modifications, a recent study of type 2 diabetes patients showed that diet helped reduce weight, while exercise helped maintain weight loss for five years. In this trial, 53 percent of patients who had initially lost 23 lb (9 percent of body weight) over 12 weeks and maintained it over one year were able to continue to maintain this weight loss and preserve muscle mass through diet and exercise over five years (12). They also benefited from a reduction in cardiovascular risk factors. In the initial 12-week period, the patients’ HbA1C was reduced from 7.5 to 6.5 percent, along with a 50 percent reduction in medications.

We know that obesity is overwhelming. It’s difficult to lose weight and even harder to reach a normal weight; however, the benefits far outweigh the risks of remaining obese. Lifestyle modifications are a must that should be discussed with your doctor. In addition, there are a range of procedures available to either help jumpstart the process, accelerate progress or to help maintain your desired weight. Choose wisely with the help of your physician.

References:

(1) JAMA 2014;311:806-814. (2) JAMA Intern Med 2015;175(8):1412-1413. (3) Am J Public Health 2015;105(9):e54-9. (4) ama-assn.org. (6) cancer.gov/cancertopics/factsheet/risk/obesity. (7) N Engl J Med 2003;348:1625-1638. (8) JAMA Oncol online June 11, 2015. (9) Clin Endocrinol 2015;83(2):147-156. (10) Cancer Prev Res 8(7):1-8. 2015 (11) fda.gov (12) ADA 2015 Abstract 58-OR.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com or consult your personal physician.

Dehydration is a topic that is often overlooked or given only cursory thought, but it’s very important. Dehydration is simple to avoid, right? Not necessarily. The problem is that we may be dehydrated prior to experiencing symptoms of thirst. In the heat of summer or while exercising, you’re more likely to think about hydration, though you may not actually hydrate enough; however, it’s relevant year-round. Complications and symptoms of dehydration can be mild to severe, ranging from constipation, mood changes, headaches and heart palpitations to heat stroke, migraines and heart attacks.

Effect on headaches and migraines

Temperature is a potential trigger for headaches and migraines. As the temperature rises by intervals of nine degrees, the risk for headaches and migraines increases by 8 percent (1). This study involved 7,054 participants from one emergency room site. Warmer temperatures can potentially reduce blood volume in the body, causing dilation of the arteries, resulting in higher risk of headaches and migraines.

In another study, those who drank four cups more water per day had significantly fewer hours of migraine pain than those who drank less (2). Headache intensity decreased as well. Anecdotally, I had a patient who experienced a potentially dehydration-induced migraine after playing sports in the sweltering heat. He had the classic aura and was treated with hydration, acetaminophen and caffeine, which helped avoid much of the suffering.

Impact on heart palpitations

Heart palpitations are very common. They are broadly felt as a racing heart rate, skipped beat, pounding sensation or fluttering. Dehydration and exercise are contributing factors (3). They occur mainly when we don’t hydrate prior to exercise. All we need to do is drink one glass of water prior to exercise and then drink during exercise to avoid palpitations. Though these are not usually life-threatening, they are anxiety-producing for patients.

Heart attacks

The Adventist Health Study, an observational study, showed a dose-response curve for men (4). In other words, group 1, which drank >five glasses of water daily, had the least risk of death from heart disease than group 2, which drank >three glasses of water daily. Those in group 3, which drank <two glasses per day, saw the least amount of benefit, comparatively. For women, there was no difference between groups 1 and 2; however, both fared better than group 3. The reason for this effect, according to the authors, may relate to blood or plasma viscosity (thickness) and fibrogen, a substance that helps clots form.

Stroke outcomes

Researchers at Johns Hopkins presented findings at the International Stroke Conference 2015 that suggest dehydrated stroke patients have a four times increased risk of having more severe outcomes between hospital admission and discharge than those without dehydration.

Dehydrated patients who presented to the emergency room within 12 hours of an ischemic (low blood flow caused usually by a clot) stroke had poorer outcomes four days later than those who were not dehydrated (5). Stroke severity was similar between the two groups, and none of these patients had kidney failure. The researchers used National Institutes of Health Stroke Scale (NIHSS) to assess daily stroke severity and used magnetic resonance imaging to calculate the number of resulting brain lesions.

The authors suggest that additional research is necessary to determine appropriate methods for rehydration that will avoid exacerbating some underlying medical conditions, like congestive heart failure.

There were some limitations of this study, including its small size, 126 patients, use of indirect markers to measure dehydration and varied MRI timing. It was also not clear whether the dehydration may have caused the strokes, or whether they were a result of medications that negatively affect the kidneys (6).

In an editorial response Dr. Jeffrey Berns, the editor-in-chief of Medscape Nephrology, noted that the above study was not one of dehydration but rather one of volume depletion (7). This is important because you can treat with the wrong substance and cause a negative effect. Dehydration results in elevated sodium in the blood and increased serum osmolarity, turning it a dark color — not to be confused with certain foods or medications that can color your urine.

However, volume depletion is a clinical diagnosis that might affect kidneys by raising the BUN/creatine ratio. If you treat the latter with water, you may cause low blood levels of sodium, which can be dangerous. Interestingly, in my clinical practice, I treat volume depletion and dehydration similarly with smoothies that predominantly contain fruits and vegetables. Regardless of which diagnosis, you may be able to treat with fluids that contain electrolytes, particulates and that are nutrient-dense.

Mood and energy levels

One small study found that mild dehydration resulted in decreased concentration, subdued mood, fatigue and headaches in women (8). In this small study, the mean age of participants was 23, and they were neither athletes nor highly sedentary. Dehydration was caused by walking on a treadmill with or without taking a diuretic (water pill) prior to the exercise. The authors concluded that adequate hydration was needed, especially during and after exercise. I would also suggest, from my practice experience, hydration prior to exercise.

Different ways to remain hydrated

Now we realize we need to stay hydrated, but how do we go about this? How much water we need to drink depends on circumstances, such as diet, activity levels, environment and other factors. It is not true necessarily that we all should be drinking eight glasses of water a day. In a review article, the authors analyzed the data but did not find adequate studies to suggest that eight glasses is supported in the literature (9). It may actually be too much for some patients.

You may also get a significant amount of water from the foods in your diet. A nutrient-dense diet, like the Mediterranean or DASH diets, has a plant-rich focus. A study mentions that diets with a focus on fruits and vegetables increases water consumption (10). As you may know, up to 95 percent of fruit and vegetable weight can be attributed to water. An added benefit is an increased satiety level without eating calorically dense foods.

The myth: Coffee is dehydrating

In one review, it was suggested that caffeinated coffee and tea don’t increase the risk of dehydration, even though caffeine is a mild diuretic (11). With moderate amounts of caffeine, the beverage has a more hydrating effect than the diuretic effect.

Thus, it is important to stay hydrated to avoid complications — some are serious, but all are uncomfortable. Diet is a great way to ensure that you get the triple effect of high amounts of nutrients, increased hydration and sense of feeling satiated without calorie-dense foods. However, don’t go overboard with water consumption, especially if you have congestive heart failure or open-angle glaucoma (12).

References:

(1) Neurology 2009 Mar 10;72(10):922-927. (2) Handb Clin Neurol 2010;97:161-172. (3) Clevelandclinic.org. (4) Am J Epidemiol 2002 May 1; 155:827-833. (5) International Stroke Conference (ISC) 2015. Abstract T MP86. Presented Feb. 12, 2015. (6) Medscape Feb. 19, 2015. (7) Medscape Mar. 27, 2015. (8) J. Nutr. Feb. 2012 142:382-388. (9) AJP -Regu Physiol 2002;283(3):R993-R1004. (10) Am J Lifestyle Med 2011;5(4):316-319. (11) Exerc Sport Sci Rev 2007;35(3):135-140. (12) Br J Ophthalmol 2005:89:1298-1301.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com or consult your personal physician.

Cancer, a word that for decades was whispered as taboo, has become front and center in the medical community. Cancer is the number one killer of Americans, at least those <85 years old, even ahead of cardiovascular disease (1). We have thought that diet may be an important component in preventing cancer. Is diet a plausible approach?

An article published in the New York Times, entitled “An Apple a Day and Other Myths,” questions the validity of diet in the prevention of cancer. This article covers cancer in general, which is a huge and daunting topic.

The article’s author references a comment by Walter Willet, M.D., a professor and chair of the Harvard School of Public Health’s Epidemiology and Nutrition Department as indicating that the research is inconsistent when it comes to fruits and vegetables. The article goes on to state that even fiber and fats may not play significant roles in cancer.

I don’t necessarily disagree with their assessment. However, I would like to emphasize that Dr. Willet also commented that there are no large, well-controlled diet studies. This leaves the door open for the possibility that diet does have an impact on cancer prevention. I would like to respond.

As Dr. Willet hinted, the problem with answering this question may lie with the studies themselves. The problem with diet studies in cancer, in particular, is that they rely mainly on either retrospective (backward-looking) or prospective (forward-looking) observational studies.

Observational studies have many weaknesses. Among them is recall bias, or the ability of subjects to remember what they did. Durability is also a problem; the studies are not long enough, especially with cancer, which may take decades to develop. Confounding factors and patient adherence are other challenges, as are the designs and end points of the studies (2). Plus, randomized controlled trials are very difficult and expensive to do since it’s difficult and much less effective to reduce the thousands of compounds in food into a focus on one nutrient. Let’s look at the evidence.

The EPIC trial
Considered the largest of the nutrition studies is the European Prospective Investigation into Cancer and Nutrition (EPIC). It is part of what the author is using to demonstrate his point that fruits and vegetables may not be effective, at least in breast cancer. This portion of the study involved almost 300,000 women from eight different European nations (3). Results showed that there was no significant difference in breast cancer occurrence between the highest quintile of fruit and vegetable consumption group compared to the lowest. The median duration was 5.4 years.
Does this study place doubt in the diet approach to cancer? Possibly, but read on. The most significant strength was its size. However, there were also many weaknesses. The researchers were trying to minimize confounding factors, but there were eight countries involved, with many different cultures, making it almost impossible to control. It is not clear if participants were asked what they were eating more often than at the study’s start. Risk stratification was also not clear; which women, for example, might have had a family history of the disease.

Beneficial studies with fruits and vegetables
Also using the same EPIC study, results showed that fruit may have a statistically significant impact on lung cancer (4). Results showed that there was a 40 percent decrease in the risk of developing lung cancer in those that were in the highest quintile of fruit consumption, compared to those in the lowest quintile. However, vegetables did not have an impact. The results were most pronounced in the northern European region. I did say the answer was complex.
Ironically, it seems that some other studies, mostly smaller studies, show potentially beneficial effects from fruits and vegetables. This may be because it is very difficult to run an intensive, well-controlled, large study.

Prostate cancer
Dean Ornish, M.D., a professor of medicine at UC San Francisco Medical School, has done several well-designed pilot studies with prostate cancer. His research has a focus on how lifestyle affects genes. In one of the studies, results of lifestyle modifications showed a significant increase in telomere length over a five-year period (5).
Telomeres are found on the end of our chromosomes; they help prevent the cell from aging, becoming unstable and dying. Shorter telomeres may have an association with diseases, such as cancer, aging and morbidity (sickness). Interestingly, the better patients adhered to the lifestyle modifications, the more telomere growth they experienced. However, in the control group, telomeres decreased in size over time. There were 10 patients in the lifestyle (treatment) group and 25 patients in the control group — those who followed an active surveillance-only approach.
In an earlier study with 30 patients, there were over 500 changes in gene expression in the treatment group. Of these, 453 genes were down-regulated, or turned off, and 48 genes were up-regulated, or turned on (6). The most interesting part is that these changes in gene transcription occurred over just a three-month period with lifestyle modifications.
In both studies, the patients had prostate cancer that was deemed at low risk of progressing into advanced or malignant prostate cancer. These patients had refused immediate conventional therapy including hormones, radiation and surgery. In both studies, the results were determined by prostate biopsy. These studies involved intensive lifestyle modifications that included a low-fat, plant-based, vegetable-rich diet. But as the researchers pointed out, there is a need for larger randomized controlled trials to confirm these results.

Cruciferous vegetables
A meta-analysis involving a group of 24 case-control studies and 11 observational studies, both types of observational trials, showed a significant reduction in colorectal cancer (7). This meta-analysis looked at the effects of cruciferous vegetables, also sometimes referred to as dark-green, leafy vegetables.
In another study that involved a case-control observational design, cruciferous vegetables were shown to significantly decrease the risk of developing multiple cancers, including esophageal, oral cavity/pharynx, breast, kidney and colorectal cancer (8). There was also a trend that did not reach statistical significance for preventing endometrial, prostate, liver, ovarian and pancreatic cancers. The most interesting part is that the comparison was modest, contrasting consumption of at least one cruciferous vegetable a week with none or less than one a month. However, we need large, randomized trials using cruciferous vegetables to confirm these results.
In conclusion, it would appear that the data are mixed in terms of the effectiveness of fruit and vegetables in preventing cancer or its progression. The large studies have flaws, and pilot studies require larger studies to validate them. However, imperfect as they are, there are results that indicate that diet modification may be effective in preventing cancer. I don’t think we should throw out the baby with the bath water.
There is no reason not to consume significant amounts of fruits and vegetables in the hopes that it will have positive effects on preventing cancer and its progression. There is no downside, especially if the small studies are correct.

References:
(1) CA Cancer J Clin. 2011;61(4):212. (2) Nat Rev Cancer. 2008;8(9):694. (3) JAMA. 2005;293(2):183-193. (4) Int J Cancer. 2004 Jan 10;108(2):269-276. (5) Lancet Oncol. 2013 Oct;14(11):1112-1120. (6) Proc Natl Acad Sci U S A. 2008 Jun 17;105(24):8369-8374. (7) Ann Oncol. 2013 Apr;24(4):1079-1087. (8) Ann Oncol. 2012 Aug;23(8):2198-2203.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com or consult your personal physician.

Ah, the warm summer months are upon us. I don’t want to be Debbie Downer, yet again, but I want to make you aware that tick season is here. In fact, according to Sam Telford, M.D., an infectious disease professor at Tufts University, we are at the peak of the season in the next few weeks to a month (1). He was talking about New England; however, the University of Rhode Island has raised its tick alert to the highest levels — red for both New England and the Mid-Atlantic states, including Long Island. Thus, it is good timing to talk about Borrelia burgdorferi, better known as the bacteria that causes Lyme disease. This bacteria is from the spirochete class and is typically found in the deer tick, also known as the blacklegged tick.

What do deer ticks look like? They are small and can be as tiny as a pencil tip or the size of a period at the end of a sentence. The CDC.gov site is a great resource for tick images and other information related to Lyme disease.

What if you have been bitten by a tick? The first thing you should do is remove it with forceps, tweezers or protected fingers (paper) as close to the skin as possible and pull slow and steady straight up. Do not crush or squeeze the tick, for doing so may spread infectious disease (2). In the study, petroleum jelly, fingernail polish, a hot kitchen match and 70 percent isopropyl alcohol all failed to properly remove a tick. The NIH recommends not removing a tick with oil (3).

When a tick is removed within 36 to 48 hours, the risk of infection is quite low, according to the CDC (4). However, a patient can be given a prophylactic dose of the antibiotic doxycycline, one dose of 200 mg, if the erythema migrans, or bulls-eye rash — a red outer ring and red spot in the center —  has not occurred, and it is within 72 hours of tick removal (5). Those who took doxycycline had significantly lower risk of developing the bulls-eye rash and thus Lyme disease; however, treatment with doxycycline did have higher incidence of nausea and vomiting than placebo.

What are the signs and symptoms of Lyme disease? There are three stages of Lyme disease: early stage, where the bacteria are localized; early disseminated disease, where the bacteria have spread throughout the body; and late-stage disseminated disease. Symptoms for early localized stage and early disseminated disease include the bulls-eye rash, which occurs in about 80 percent of patients, with or without systemic symptoms of fatigue (54 percent), muscle pain and joint pain (44 percent), headache (42 percent), neck stiffness (35 percent), swollen gland (23 percent) and fever (16 percent) (6).

Early disseminated disease may cause neurological symptoms such as meningitis, cranial neuropathy (Bell’s palsy) and motor or sensory radiculoneuropathy (nerve roots of spinal cord). Late disseminated disease can cause Lyme arthritis (inflammation in the joints), heart problems, facial paralysis, impaired memory, numbness, pain and decreased concentration (3).

How do we prevent this disease? According to the CDC, we should wear protective clothing, spray ourselves with insect repellent that includes at least 20 percent DEET, and treat our yards (4). Always check your skin for ticks after walking through a woody or tall grassy area. Many of us on Long Island have ticks in the backyard. My golden retriever, Buddy, whom I loved dearly, died of Lyme complications, and my mom’s golden retriever has tested positive.

DIAGNOSIS OF LYME DISEASE
Many times Lyme disease can be diagnosed within the clinical setting. However, when it comes to serologic or blood tests, the CDC recommends an ELISA test followed by a confirmatory Western blot test (4). However, testing immediately after being bitten by a tick is not useful, since the test will tend to be negative, regardless of infection or not (7). It takes about one to two weeks for IgM antibodies to appear and two to six weeks for IgG antibodies (8). These antibodies sometimes remain elevated even after successful treatment with antibiotics.

THE CARDIAC IMPACT
What are some of the complications of Lyme disease? Lyme carditis is a rare complication affecting 1.1 percent of those with disseminated disease, but it can result in sudden cardiac death due to second or third degree atrioventricular (AV) node conduction (electrical) block. Among the 1.1 percent who had Lyme carditis, there were five sudden deaths (9). If there are symptoms of chest pain, palpitations, lightheadedness, shortness of breath or fainting, then clinicians should suspect Lyme carditis.

DOES CHRONIC LYME DISEASE EXIST?
There has been a debate about whether there is something called “chronic Lyme” disease. The research, unfortunately, has not shown consistent results that indicate that it exists. In the most recent report, chronic Lyme is refuted (10). In the analysis, the authors comment that the definition of chronic Lyme disease is obfuscated and that extended durations of antibiotics do not prevent or alleviate post-Lyme syndromes, according to several prospective trials. The authors do admit that there are prolonged neurologic symptoms in a subset population that may be debilitating even after the treatment of Lyme disease. These authors also suggest that there may be post-Lyme disease syndromes with joint pain, muscle pain, neck and back pain, fatigue and cognitive impairment.

When asked what was more important, longevity or healthy aging (quality of life), more people choose the latter. Why would you want to live a long life, but be miserable? Well, it turns out the two components are not mutually exclusive. I would like you to ponder the possibility of a third choice, “all of the above.” Would you change your answer and, instead of making a difficult choice between the first two, choose the third?
I frequently use the example of Jack LaLanne, a man best known for popularizing fitness. He followed and preached a healthy lifestyle, which included diet and exercise. He was quite a motivator for many and ahead of his time. He died at the ripe old age of 96.

This brings me to my next point, which is that the number of 90-year-olds is growing by leaps and bounds.

According to the National Institutes of Health, those who were more than 90 years old increased by 2.5 times over a 30-year period from 1980 to 2010 (1). This group is among what researchers refer to as the “oldest-old,” which includes those age 85 and older.

What do these patients have in common? According to one study, they tend to have fewer chronic morbidities or diseases. Thus, they tend to have a better quality of life with a greater physical functioning and mental acuity (2).

In a recent study of centenarians, genetics played a significant role. Characteristics of this group were that they tended to be healthy and then die rapidly, without prolonged suffering (3).

Another benchmark is the amount of health care dollars spent in their last few years. Statistics show that the amount spent for those who were in their 60s and 70s was significantly higher, three times as much, as for centenarians in their last two years (4).

Factors that predict one’s ability to reach this exclusive club may involve both genetics and lifestyle choices.

One group of people in the U.S. who lives longer lives on average than most is Seventh-day Adventists. We will explore why this might be the case and what lifestyle factors could increase our potential to maximize our healthy longevity. Exercise and diet may be key components of this answer. Now that we have set the tone, let’s look at the research.

EXERCISE
For all those who don’t have time to exercise or don’t want to spend the time, this next study is for you. We are told time and time again to exercise. But how much do we need, and how can we get the best quality? In a recent study, the results showed that 5 to 10 minutes of daily running, regardless of the pace, can have a significant impact on lifespan by decreasing cardiovascular mortality and all-cause mortality (5).
Amazingly, even if participants ran less than six miles per week at a pace slower than 10-minute miles, and even if they ran only one to two days a week, there was still a decrease in mortality compared to nonrunners. Here is the kicker: those who ran for this very short of amount of time potentially added three years to their lifespan. There were 55,137 participants ranging in age from 18 to 100 years old.
An accompanying editorial to this study noted that more than 50 percent of people in the United States do not meet the current recommendation of at least 30 minutes of moderate exercise per day (6). Thus, this recent study suggests an easier target that may still provide significant benefits.

DIET
A long-standing paradigm is that we need to eat sufficient animal protein. However, there have been cracks developing in this façade of late, especially as it relates to longevity. In a recent observational study using NHANES III data, results show that those who ate a high-protein diet (greater 20 percent from protein) had a twofold increased risk of all-cause mortality, a four times increased risk of cancer mortality and a four times increased risk of dying from diabetes (7). This was over a considerable duration of 18 years and involved almost 7,000 participants ranging in age at the start of the study from 50 to 65.
However, this did not hold true if the protein source was from plants. In fact, a high-protein plant diet may reduce the risks, not increase them. The reason for this effect, according to the authors, is that animal protein may increase insulin growth factor-1 and growth hormones that have detrimental effects on the body.
Interestingly, those who are over the age of 65 may benefit from more animal protein in reducing the risk of cancer. However, there was a significantly increased risk of diabetes mortality across all age groups eating a high animal protein diet. The researchers therefore concluded that lower animal protein may be wise at least during middle age.
The Adventists Health Study 2 trial reinforced this data. It looked at Seventh-day Adventists, a group whose emphasis is on a plant-based diet, and found that those who ate animal protein up to once a week had a significantly reduced risk of dying over the next six years compared to those who were more frequent meat eaters (8). This was an observational trial with over 73,000 participants and a median age of 57 years old.

INFLAMMATION
You may have heard the phrase that inflammation is the basis for more than 80 percent of chronic disease. But how can we quantify this into something tangible? In the Whitehall II study, a specific marker for inflammation was measured, interleukin-6. The study showed that higher levels did not bode well for participants’ longevity (9). In fact, if participants had elevated IL-6 (>2.0 ng/L) at both baseline and at the end of the 10-year follow-up period, their probability of healthy aging decreased by almost half.
The takeaway from this study is that IL-6 is a relatively common biomarker for inflammation that can be measured with a simple blood test offered by most major laboratories. This study involved 3,044 participants over the age of 35 who did not have a stroke, heart attack or cancer at the beginning of the study.
The bottom line is that, although genetics is important for longevity, so too are lifestyle choices. A small amount of exercise, specifically running, can lead to a substantial increase in healthy lifespan. While calories are not equal, protein from plants may trump protein from animal sources in reducing the risk of mortality from all-cause, diabetes and heart disease.
This does not necessarily mean that one needs to be a vegetarian to see the benefits. IL-6 may be a useful marker for inflammation, which could help predict healthy or unhealthy outcomes. Thus, why not have a discussion with your doctor about testing to see if you have an elevated IL-6? Lifestyle modifications may be able to reduce these levels.

REFERENCES:
(1) nia.nih.gov. (2) J Am Geriatr Soc. 2009;57:432-440. (3) Future of Genomic Medicine (FoGM) VII. Presented March 7, 2014. (4) CDC.gov. (5) J Am Coll Cardiol. 2014;64:472-481. (6) J Am Coll Cardiol. 2014;64:482-484. (7) Cell Metab. 2014;19:407-417. (8) JAMA Intern Med. 2013;173:1230-1238. (9) CMAJ. 2013;185:E763-E770.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.