This is the first of a two-part series on salt. Salt, or sodium, is one of the most pervasive essential nutrients in our diet. While we need exogenous (external) salt, the debate on the amount we need continues. Are we getting too much or too little? A recently published study would indicate that the extremes – too much and too little – are dangerous. The newspaper headlines from this study suggest that reducing sodium may be harmful.

Is this true or is it hyperbolized? We will investigate this study in much more detail. However, I will say this: Many Americans get far more than the recommended amount of sodium intake, regardless of which guidelines you are using. Very few individuals suffer from dietary sodium deficiency.

So what are the guidelines, and how much are Americans consuming on average? According to the Centers for Disease Control, the U.S. government recommends no more than 2,300 mg of sodium per day (1). But for those who are over 50 years old, are African American or who have high blood pressure, diabetes or chronic kidney disease, then sodium should be restricted to less than 1,500 mg per day. One teaspoon of salt is the equivalent of 2,300 mg of sodium. The World Health Organization recommends less than 2,000 mg per day (2) and the American Heart Association recommends less than 1,500 mg for everyone (3). This is approximately two-thirds of a teaspoon of salt. The average amount Americans consume is 3,300 mg per day.

This is not about the salt shaker, though. Most people protest that they don’t use salt or processed foods, which are notoriously high in sodium. Sodium lurks in many places, though.

What are the potential obscure sources of sodium? Participants in a recent study were able to identify that processed foods were a major source of sodium and its excess; however, less than one-third knew that bread, pasta, cereal and cheese were major sources (4). Other sources include soups (yes, even many “healthy” soups); many frozen foods; condiments, including salad dressings; and sauces, especially spaghetti sauces, regardless of whether or not they are organic. So, if we include bread, sauces and cheese, that makes pizza one of the worst offenders! Also remember that eating out significantly contributes to increased sodium intake.

I had an interesting situation occur recently with a patient. After one month, he came back for a visit. During that month he went on vacation for a couple of weeks. We looked at his body composition. While he gained 5 pounds, what was surprising was that he actually lost 12 pounds of body fat, but gained 17 pounds of water weight. He had said he was eating really well. Unfortunately, he was unable to control for salt intake while eating out. Thus, as a consequence, he had significantly swollen ankles and significantly increased blood pressure that was uncontrolled. Even over a short period of time, salt can have a large impact on the body.

What are the potential short-term symptoms of too much salt? They can include headaches, dizziness, dehydration, edema (swelling), arrhythmias and weight gain.

Too much salt can increase our risk of disease or exacerbate pre-existing diseases. For instance, salt can raise blood pressure and contribute to kidney stones, osteoporosis, diabetes and chronic kidney disease. It can also exacerbate autoimmune disease, such as rheumatoid arthritis and Sjögren’s, and increase the risk of cardiovascular disease and mortality from CVD and all-causes (5). There are several studies that emphasize the impact of sodium on cardiovascular disease globally.

Also, don’t fall for the idea that when we exercise most of us need sodium replenishment. If we exercise strenuously – on the level of football players or marathon runners – then, yes, we need more sodium (6). However, for the rest of us who exercise no more than 90 minutes every day at a vigorous pace, it is unlikely that we require additional sodium.

One of the most frequent questions I am asked is whether there are any benefits from using Himalayan salt, kosher salt or sea salt instead of regular table salt. When we talk about symptoms or disease consequences from excessive salt consumption, it doesn’t matter whether the source is a more sophisticated form of salt. The effects are the same. Salt is salt! Let’s look at the evidence.

Impact of salt extremes

In the Prospective Urban Rural Epidemiology study, an observational study, results showed that participants who were at the “extremes,” those who had high amounts of sodium and those who had low amounts of sodium, all experienced higher risk of cardiovascular events and all-cause death (7). When blood pressure was factored in, those in the higher sodium group did not have significantly increased cardiovascular events.

There were three groups in the study: those who excreted high amounts of sodium, defined as greater than 6,000 mg or the upper “extreme”; moderate amounts, defined as 3,000 mg to 6,000 mg; and low amounts, defined as less than 3,000 mg or the lower “extreme.” There were over 100,000 participants from 17 countries. The duration of the study was approximate 3.5 years. The amounts of urinary sodium excreted were based on an estimated 24-hour urine output, which is a way of measuring sodium intake. The results also showed that increasing potassium levels greater than 1,500 mg had the opposite effect of sodium, decreasing the risk of cardiovascular events and death. The potassium levels were a 24-hour estimate, as well.

A weakness of this study was that data were based on one urinary sodium excretion in the morning and then extrapolated out to 24-hour urine output, which is considered a better biomarker. Nonetheless, there was only one reading per participant and this was not a 24-hour reading. Thus, this is not a very accurate way to measure sodium, since it was a single snapshot view.

Even if one did suffer from not enough sodium, causing hyponatremia (low sodium in the blood), eating more from the diet might perpetuate increased thirst and, thus, potential fluid overload. This could lead to edema and even lower sodium.

Therefore, from this study, we don’t know if sodium of less than 3,000 mg per day is dangerous. There were two times more participants who had high sodium excretion compared to low sodium excretion, and there were seven times as many participants with sodium levels greater than 4,000 mg than those with levels less than 3,000 mg. Granted, low sodium may be an issue, but what is really too low? We don’t know, and it does not happen often.

We as a society consume much more than any of the guidelines suggest. It would be a disservice to believe that adding more salt to your diet would not be harmful or that not reducing your intake is okay. So don’t reach for the salt shaker and read labels carefully. Rather reach for foods that have high levels of potassium and naturally occurring sodium such as green leafy vegetables.

References:

(1) www.cdc.gov. (2) www.who.int. (3) www.heart.org. (4) Appetite. 2014;83C:97-103. (5) www.uptodate.com. (6) Evid Based Nurs. 2014;17:92. (7) N Engl J Med. 2014;371:612-623.

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.

Weight loss should be a rather simple concept. It should be solely dependent on energy balance: the energy (kilocalories) we take in minus the energy (kilocalories) we burn should result in weight loss if we burn more calories than we consume. However, it is much more complicated. Frankly, there are numerous factors that contribute to whether people who want or need to lose weight can.

The factors that contribute to weight loss may depend on stress levels, as I noted in my previous article, “Ways to counter chronic stress.” High stress levels can contribute to metabolic risk factors such as central obesity with the release of cortisol, the stress hormone (1). Therefore, hormones contribute.

Another factor in losing weight may have to do with our motivators. We will investigate this further.

And we need successful weight management, especially when approximately 70 percent of the American population is overweight or obese and more than one-third is obese (2).

Recently, obesity in and of itself was proclaimed a disease by the American Medical Association. Even if you don’t agree with this statement, excess weight has consequences, including chronic diseases such as cardiovascular disease, diabetes, osteoarthritis and a host of others, including autoimmune diseases. Weight has an impact on all-cause mortality and longevity.

It is hotly debated as to which approach is best for weight loss. Is it lifestyle change with diet and exercise, medical management with weight loss drugs, surgical procedures or even supplements? The data show that, while medication and surgery may have their places, they are not replacements for lifestyle modifications; these modifications are needed no matter what route is followed.

But the debate continues as to which diet is best. We would hope patients would not only achieve weight loss, but also overall health.

Let’s look at the evidence.

Low-carbohydrate diets versus low-fat diets

Is a low-carbohydrate, high-fat diet a fad? It may depend on diet composition. In a newly published study of a randomized controlled trial, the gold standard of studies, results showed that a low-carbohydrate diet was significantly better at reducing weight than low-fat diet, by a mean difference of 3.5 kg lost (7.7 pounds), even though calories were similar and exercise did not change (3).

The authors also note that the low-carbohydrate diet reduced cardiovascular disease risk factors in the lipid (cholesterol) profile, such as decreasing triglycerides (mean difference 14.1 mg/dl) and increasing HDL (good cholesterol). Patients lost 1.5 percent more body fat on the low-carbohydrate diet, and there was a significant reduction in inflammation biomarker, C-reactive protein. There was also a reduction in the 10-year Framingham risk score. However, there was no change in LDL (bad cholesterol) levels or in truncal obesity in either group. This study was 12 months in duration with 148 participants, predominantly women, with a mean age of 47, none of whom had cardiovascular disease or diabetes, but all of whom were obese or morbidly obese (BMI 30-45 kg/m2).

Although there were changes in biomarkers, there was a dearth of cardiovascular disease clinical endpoints. This begs the question: Does a low-carbohydrate diet really reduce the risk of developing cardiovascular disease or its subsequent complications? The authors indicated this was a weakness since it was not investigated.

Digging deeper into the diets used, it’s interesting to note that the low-fat diet was remarkably similar to the standard American diet; it allowed 30 percent fat, only 5 percent less than the 35 percent baseline for the same group. In addition, it replaced the fat with mostly refined carbohydrates, including only 15 to 16 g/day of fiber.

The low-carbohydrate diet participants took in an average of 100 fewer calories per day than participants on the low-fat diet, so it’s no surprise that they lost a few more pounds over a year’s time.

Patients in both groups were encouraged to eat mostly unsaturated fats, such as fish, nuts, avocado and olive oil.

As David Katz, M.D., founding director of Yale University’s Prevention Research Center noted, this study was more of a comparison of low-carbohydrate diet to a high-carbohydrate diet than a comparison of a low-carbohydrate diet to a low-fat diet (4).

Another study actually showed that a Mediterranean diet, higher in fats with nuts or olive oil, compared to a low-fat diet showed a significant reduction in cardiovascular events — clinical endpoints not just biomarkers (5). However, both of these studies suffer from the same deficiency: comparing a low-carbohydrate diet to a low-fat diet that’s not really low in fat.

Diet comparisons

Interestingly, in a meta-analysis (a group of 48 RCTs), the results showed that whether a low-carbohydrate diet (including the Atkins diet) or a low-fat diet (including the Ornish plant-based diet), the results showed similar amount of weight loss compared to no intervention at all (6). Both diet types resulted in about 8 kgs (17.6 pounds) of weight loss at six months versus no change in diet. However, this meta-analysis did not make it clear whether results included body composition changes or weight loss alone.

In an accompanying editorial discussing the above meta-analysis, the author points out that it is unclear whether a low-carbohydrate/high animal protein diet might result in adverse effects on the kidneys, loss of calcium from the bones or other potential deleterious health risks. The author goes on to say that for overall health and longevity and not just weight loss, micronutrients may be the most important factor, which are in nutrient-dense foods.

A recent Seventh-day Adventist trial would attest to this emphasis on a micronutrient-rich, plant-based diet with limited animal protein. It resulted in significantly greater longevity compared to a macronutrient-rich animal protein diet (7).

Psyche

Finally, the type of motivator is important in whatever our endeavors. Weight loss goals are no exception. Let me elaborate. A recently published study followed West Point cadets from school to many years after graduation and noted who reached their goals (8). The researchers found that internal motivators and instrumental (external) motivators were very important.

The soldiers who had an internal motivator, such as wanting to be a good soldier, were more successful than those who focused on instrumental motivators, such as wanting to become a general. Those who had both internal and instrumental motivators were not as successful as those with internal motivators alone. In other words, having internal motivators led to an instrumental consequence of advancing their careers.

When it comes to health, an instrumental motivator, such weight loss, may be far less effective than focusing on an internal motivator, such as increasing energy or decreasing pain, which ultimately could lead to an instrumental consequence of weight loss.

There is no question that dietary changes are most important to achieving sustained weight loss. However, we need to get our psyches in line for change. Hopefully, when we choose to improve our health, we don’t just focus on weight as a measure of success. Weight loss goals by themselves tend to lead us astray and to disappoint, for they are external motivators. Focus on improving your health by making lifestyle modifications. This tends to result in a successful instrumental consequence.

References:

(1) Psychoneuroendocrinol Online. 2014 April 12. (2) JAMA 2012;307:491–497. (3) Ann Intern Med. 2014;161:309-318. (4) Huffington Post. 2014 Sept. 2. (5) N Engl J Med. 2014;370:886. (6) JAMA. 2014;312:923-933. (7) JAMA Intern Med. 2013;173:1230-1238. (8) Proc Natl Acad Sci U S A. 2014;111:10990-10995.

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.

The end of the Labor Day holiday represents the unofficial end of summer, the beginning of the academic calendar and noticeably shorter daylight hours. The pace of life tends become more hectic. Although some stress is valuable to help motivate us and keep our minds sharp, high levels of constant stress can have detrimental effects on the body.

It is very likely that there is a mind-body connection when it comes to stress. In other words, it may start in the mind, but it can lead to acute or chronic disease promotion. Stress can also play a role with your emotions, causing irritability and outbursts of anger, and possibly leading to depression and anxiety. Stress symptoms are hard to distinguish from other disorders but can include stiff neck, headaches, stomach upset and difficulty sleeping. Stress may also be associated with cardiovascular disease, with an increased susceptibility to infection from viruses causing the common cold and with cognitive decline and Alzheimer’s (1).

A stress steroid hormone called cortisol is released from the adrenal glands and can have beneficial effects in small bursts. We need cortisol in order to survive. Some of cortisol’s functions include raising the glucose (sugar) levels when they are low and helping reduce inflammation and stress levels (2). However, when cortisol gets out of hand, higher chronic levels may cause inflammation, leading to disorders such as cardiovascular disease, as recent research suggests. Let’s look at the evidence.

Inflammation may be a significant contributor to more than 80 percent of chronic diseases, so it should be no surprise that inflammation is an important factor with stress. In a recent meta-analysis (a group of two observational studies), high levels of C-reactive protein, a biomarker for inflammation, were associated with increased psychological stress (3).

What is the importance of CRP? It may be related to heart disease and heart attacks. This study involved over 73,000 adults who had their CRP levels tested. The research went further to suggest that increased levels of CRP may result in more stress and also depression. With CRP higher than 3.0 there was a greater than twofold increase depression risk. The researchers suggest that CRP may heighten stress and depression risk by increasing levels of different proinflammatory cytokines, inflammatory communicators among cells (4).

In one recent study, results suggested that stress may influence and increase the number of hematopoietic stem cells (those that develop of all forms of blood cells), resulting in specifically an increase in inflammatory white blood cells (5). The researchers suggest that this may lead to these white blood cells accumulating in atherosclerotic plaques in the arteries, which ultimately could potentially increase the risk of heart attacks and strokes. Chronic stress overactivates the sympathetic nervous system — our “fight or flight” response — which may alter the bone marrow where the stem cells are found. This research is preliminary and needs well-controlled trials to confirm these results.

Stress may increase the risk of colds and infection. Cortisol over the short term is important to help suppress the symptoms of colds, such as sneezing, cough and fever. These are visible signs of the immune system’s infection-fighting response. However, the body may become resistant to the effects of cortisol, similar to how a type 2 diabetes patient becomes resistant to insulin. In one study of 296 healthy individuals, participants who had stressful events and were then exposed to viruses had a higher probability of catching a cold. It turns out that these individuals also had resistance to the effects of cortisol. This is important because those who were resistant to cortisol had more cold symptoms and more proinflammatory cytokines (6).

When we measure cortisol levels, we tend to test the saliva or the blood. However, these laboratory findings only give one point in time. Thus, when trying to determine if raised cortisol may increase cardiovascular risk, the results are mixed. However, in a recent study, measuring cortisol levels from scalp hair was far more effective (7). The reason for this is that scalp hair grows slowly, and therefore it may contain three months’ worth of cortisol levels. The study showed that those in the highest quartile of cortisol levels were at a three-times increased risk of developing diabetes and/or heart disease compared to those in the lowest quartile. This study involved older patients between the ages of 65 and 85.

Lifestyle plays an important role in stress at the cellular level, specifically at the level of the telomere, which determines cell survival. The telomeres are to cells as the plastic tips are to shoelaces; they prevent them from falling apart. The longer the telomere, the slower the cell ages and the longer it survives. In a recent study, those women who followed a healthy lifestyle — one standard deviation over the average lifestyle — were able to withstand life stressors better since they had longer telomeres (8).

This healthy lifestyle included regular exercise, a healthy diet and a sufficient amount of sleep. On the other hand, the researchers indicated that those who had poor lifestyle habits lost substantially more telomere length than the healthy lifestyle group. The study followed women 50 to 65 years old over a one-year period.

In another study, chronic stress and poor diet (high sugar and high fat) together increased metabolic risks, such as insulin resistance, oxidative stress and central obesity, more than a low-stress group eating a similar diet (9). The high-stress group was caregivers, specifically those caring for a spouse or parent with dementia. Thus, it is especially important to eat a healthy diet when under stress.

Interestingly, in terms of sleep, the Evolution of Pathways to Insomnia Cohort study shows that those who deal with stressful events directly are more likely to have good sleep quality. Using medication, alcohol or, most surprisingly, distractors to address stress all resulted in insomnia after being followed for one year (10). Cognitive intrusions or repeat thoughts about the stressor also resulted in insomnia.

Psychologists and other health care providers sometimes suggest distraction from a stressful event, such as television watching or other activities, according to the researchers. However, this study suggests that this may not help avert chronic insomnia induced by a stressful event. The most important message from this study is that how a person reacts and deals with a stressors may determine whether they suffer from insomnia.

Constant stress is something that needs to be recognized. If not addressed, it can lead to suppressed immune response or increased levels of inflammation. CRP is an example of an inflammatory biomarker that may actually increase stress. In order to address chronic stress and lower CRP, it is important to adopt a healthy lifestyle that includes sleep, exercise and diet modifications. A good lifestyle may be protective against cell aging when exposed to stressors.

References:

(1) Curr Top Behav Neurosci. 2014 Aug. 29. (2) Am J Physiol. 1991;260(6 Part 1):E927-E932. (3) JAMA Psychiatry. 2013;70:176-184. (4) Chest. 2000;118:503-508. (5) Nat Med. 2014;20:754-758. (6) Proc Natl Acad Sci U S A. 2012;109:5995-5999. (7) J Clin Endocrinol Metab. 2013;98:2078-2083. (8) Mol Psychiatry Online. 2014 July 29. (9) Psychoneuroendocrinol Online. 2014 April 12. (10) Sleep. 2014;37:1199-1208.

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.

With diabetes, we tend to concentrate on the stabilization of the disease as a whole. This is a good thing. However, there is not enough attention spent on microvascular (small vessel disease) complications of diabetes, specifically diabetic retinopathy, which is an umbrella term. There are at least three different disorders that make up diabetic retinopathy. These are dot and blot hemorrhages, proliferative diabetic retinopathy and diabetic macular edema. The latter two are the most likely disorders to cause vision loss. Our focus for this article will be on diabetic retinopathy as a whole and diabetic macular edema.

Diabetic retinopathy is the No. 1 cause of vision loss in those who are of working age, 25 to 74 years old (1). Risk factors include duration of diabetes, not well-controlled glucose (sugars), type 1 more than type 2, smoking, high blood pressure, kidney disease, pregnancy and high cholesterol (2).

What is diabetic macula edema, also referred to as DME? This disorder is edema, or swelling, due to extracellular fluid accumulating in the macula (3). The macula is a yellowish oval spot in the central portion of the retina — in the inner segment of the back of the eye — and it is sensitive to light. The macula is the region with greatest visual acuity. Hence, when fluid builds up, there is potential loss of vision.

Whew! Did you get all that? If not, to summarize: diabetic macula edema is fluid in the back of the eye that may cause vision loss. DME affects approximately 1 in 25 patients with diabetes according to a recent study (4). However, the results also showed that this number is significantly greater (2.6 times) in blacks compared to non-Hispanic whites. And the highest risk factor for DME was for those with the longest duration of diabetes. Ironically, an oral class of drugs, thiazolidinediones, which includes rosiglitazone (Avandia) and pioglitazone (Actos), used to treat type 2 diabetes may actually increase the risk of DME. However, the results on this are conflicting.

DME is traditionally treated with lasers. But intravitreal (intraocular — within the eye) injections of a medication known as ranibizumab (Lucentis) may be a route that is as effective as laser. Studies suggest that injections alone may be as effective as injections plus laser treatments, though the studies are in no way definitive. Unfortunately, many patients are diagnosed with DME after it has already caused vision loss. If not treated after having DME for a year or more, patients can experience permanent loss of vision (5).

In a cross-sectional study (a type of observational study) using NHANES data from 2005-08, among patients with DME, only 45 percent were told by a physician that the diabetes had affected their eyes (6). Approximately 46 percent of patients reported that they had not been to a diabetic nurse educator, nutritionist or dietician in more than a year — or never. The problem is that the symptoms of vision loss don’t necessarily occur until the latter stages of the disorder. According to the authors, there needs to be an awareness campaign about the importance of getting your eyes examined on an annual basis if you have diabetes. Many patients are unaware of the association between vision loss and diabetes.

According to a study, there is good news in that the percentage of patients reporting visual impairment from 1997 to 2010 decreased (7). However, the absolute number of patients with vision loss has actually continued to grow, but at a lesser rate than diabetes as a disease has grown.

Treatment laser and injection

There seems to be a potential paradigm shift in the making for the treatment of DME. Traditionally, patients had been treated with lasers. The results from a recent randomized controlled trial, the gold standard of studies, showed that intravitreal (delivery directly into the eye) injections with ranibizumab (Lucentis), whether given prompt laser treatments or treatments delayed for at least 24 weeks were equally effective in treating DME (8).

In fact, some in the delayed group, 56 patients or about half, never even required laser treatments at all. Unfortunately, intravitreal injections may be used as frequently as every four weeks. Though in practice, ophthalmologists generally are able to inject patients with the drug less frequently. However, the advantage of receiving prompt laser treatments along with the injections was a reduction in the median number of injections by four over a five-year period.

Increased risk with diabetes drugs

You would think that drugs to treat type 2 diabetes would prevent DME from occurring as well. However, in the THIN trial, a retrospective (backward-looking) study, a class of diabetes drugs, thiazolidinediones, including Avandia and Actos, actually increased the occurrence of DME compared to those who did not use these oral medications (9). Those receiving these drugs had a 1.3 percent incidence of DME at year one, whereas those who did not had a 0.2 percent incidence. This incidence was persistent through the 10 years of follow-up. To make matters worse, those who received both thiazolidinediones and insulin had an even greater incidence of DME. There were 103,000 diabetes patients reviewed in this trial. It was unclear whether the drugs, because they were second line treatments, or the severity of the diabetes itself may have caused these findings.

This is in contrast to a previous
ACCORD eye substudy, a cross-sectional analysis, which did not show an association between thiazolidinediones and DME (10). This study involved review of 3,473 participants who had photographs taken of the fundus (the back of the eye).

What does this ultimately mean? Both of these studies were not without weaknesses. It was not clear how long the patients had been using the thiazolidinediones in either study or whether their sugars were controlled and to what degree. The researchers were also unable to control for all other possible confounding factors (11). Thus, there needs to be a prospective trial done to sort out these results.

Diet

The risk of progression of diabetic retinopathy was significantly lower with intensive blood sugar controls using medications, one of the few highlights of the ACCORD trial (12). Medication-induced intensive blood sugar control also resulted in more increased mortality and no significant change in cardiovascular events. But an inference can be made: a nutrient-dense, plant-based diet that intensively controls blood sugar is likely to decrease the risk of diabetic retinopathy complications (13) (14).

The best way to avoid diabetic retinopathy is obviously to prevent diabetes. Barring that, it’s to have sugars well controlled. If you or someone you know has diabetes, it is imperative that they get a yearly eye exam from an ophthalmologist so that DME and diabetic retinopathy, in general, is detected as early as possible, before permanent vision loss can occur. It is especially important for those diabetes patients who are taking the oral diabetes class thiazolidinediones, which include rosiglitazone (Avandia) and pioglitazone (Actos).

References:

(1) Diabetes Care. 2014;37 (Supplement 1):S14-S80. (2) JAMA. 2010;304:649-656. (3) www.uptodate.com. (4) JAMA Ophthalmol online. 2014 Aug. 14. (5) www.aao.org/ppp. (6) JAMA Ophthalmol. 2014;132:168-173. (7) Morb Mortal Wkly Rep. 2011;60:1549-1553. (8) ASRS. Presented 2014 Aug. 11. (9) Arch Intern Med. 2012;172:1005-1011. (10) Arch Ophthalmol. 2010 March;128:312-318. (11) Arch Intern Med. 2012;172:1011-1013. (12) www.nei.nih.gov. (13) OJPM. 2012;2:364-371. (14) Am J Clin Nutr. 2009;89:1588S-1596S.

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 medicalcompassmd.com.

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 medicalcompassmd.com and/or consult your personal physician.

Niacin has recently become a highly contested drug. In my last article, “Reducing triglycerides,” I mentioned that niacin has powerful effects to treat elevated triglycerides, but that the clinical benefit of this effect is questionable.  Here, I will expand on issues related to niacin.

What is niacin? It is a B vitamin, specifically B3.  It is one of the few supplements that is regulated by the FDA in higher doses as a medication.  It is also known as nicotinic acid and is a coenzyme involved in oxidation-reduction, where electrons are exchanged.  These reactions provide a source of energy  for organisms (1).

Just like with triglycerides, niacin seems to have a powerful effect on HDL  “good” cholesterol, by raising HDL levels as much 30-35 percent (2). While this is an impressive number, once again, it has become debatable whether this raising of HDL is clinically beneficial.

In several recent trials, niacin showed unexpectedly disappointing results in reducing the potential for cardiovascular disease and events. It also demonstrated significant side effects.  In other words, this is not a harmless drug.

Interestingly, as the benefit of niacin for cardiovascular disease has been debated, the number of scripts has increased almost threefold, or 200 percent, in the seven years from 2002 to 2009, according to IMS data for both the U.S. and Canada (3). The majority of the scripts were for extended-release niacin (Niaspan). The rest were mainly for Simcor (simvastatin-niacin combination) and Advicor (lovastatin-niacin combination).

Let’s look at the evidence.

Is raising HDL beneficial or not?

The paradigm has always been that higher HDL is better, but this may not be the case. It is not the first time that HDL’s protectiveness has been debated. An observational study showed that those who have genetically high levels of HDL may not benefit any more than those with normal levels (4). I wrote about this in a separate article entitled “New cholesterol guidelines released,” which can be found on northshoreoflongisland.com.

In a recent randomized controlled trial, the HPS2-THRIVE study, the results showed an increase of 6 mg/dL in HDL levels and a decrease of 10 mg/dL in LDL, “bad” cholesterol, when extended-release niacin plus laropiprant was added to statin therapy (5). This is considered by some to be a relatively small change. Also, there was no reduction in vascular events seen with the combination, even though there was improvement in both HDL and LDL when compared to the placebo.

Laropiprant is a drug used to help reduce the flushing with niacin. The dose used was 2 g of extended-release niacin and 40 mg of laropiprant. The demographics included a patient population that had vascular disease, and therefore was at greater risk of vascular events, such as non-fatal heart attacks, strokes, arterial revascularization and mortality from cardiovascular disease. There were over 25,000 patients involved in the study, and its duration was 3.9 years. LDL was already low in the participants at the start of the trial.

To make matters worse, the serious side effects were greater with the extended-release niacin compared to the placebo. There was a greater propensity toward diabetes — 32 percent relative increase — as well as exacerbation of diabetes — 55 percent increase in impaired sugar or glucose control — in patients who already had the disease. There were also increases in ulcers and diarrhea by 28 percent; muscle damage and gout by 26 percent; rashes and ulcerations by 67 percent; gastrointestinal bleeding or other bleeds by 38 percent; and infection rates by 22 percent. Using niacin to raise HDL may be ineffective, at least in vascular patients — those with atherosclerosis — who already have low LDL. It does not foretell what happens in patients with high LDL at the start.

Other studies have shown questionable efficacy and increased adverse events with niacin use in raising HDL levels to limit cardiovascular events. In the AIM-HIGH study, similarly disappointing results were seen. When extended-release niacin was added to patients with stable coronary artery disease, high triglycerides and low HDL who were already on statins, there was no clinical change in cardiovascular events (6).

Also, there were more serious adverse effects seen in the niacin group compared to the placebo group in a post-hoc analysis (7). These side effects included gastrointestinal disorders, infection, and infestations. However, there was no difference in bleed or hemorrhage, though the absolute number was small.

In yet another study, this a meta-analysis of 39 studies, including HPS2-THRIVE and AIM-HIGH, both mentioned previously, comparing the benefits of niacin, cholesteryl ester transfer protein inhibitors, and fibrates, the results showed that even though these drugs may raise HDL levels, there was no improvement in terms of cardiovascular endpoints when added to statin therapy (8). There were about 117,000 patients involved in the meta-analysis. The drugs and drug classes, niacin, CETP and fibrates, did not demonstrate any reduction in all-cause mortality or coronary heart disease mortality, nor did they reduce heart attacks or stroke risk. These drugs were added to statins as adjunct therapy.

Possible HDL explanation

Investigating a theory as to why raising HDL may not be effective when using niacin, a small study looked at cholesterol efflux capacity — the ability of HDL to garner cholesterol from macrophages, a type of white blood cells, compared to the HDL inflammatory index (9). The results showed that cholesterol efflux capacity may be a better indicator for vascular disease than HDL levels. There was an increase in HDL-C, where C stands for cholesterol, but no change in HDL inflammatory index, nor cholesterol efflux capacity, when niacin was used.

In conclusion, if you are on niacin to raise HDL levels and are already on a statin, you may want to talk to your physician about the evidence that refutes the clinical benefits in reducing cardiovascular events. The European Union has recently banned the use of niacin-laropiprant combination (10). Niacin alone does not seem to be harmless either. Whether HDL is as important as we thought is now in debate. Know that a change in a biomarker, such as HDL levels, is not synonymous with better clinical outcomes. This disappointing clinical result also holds true for niacin’s effects on triglycerides.

This article is only addressing niacin in regard to HDL and the cholesterol profile in general, not other roles for the drug. Of course, never discontinue your medication without first discussing it with your doctor.

References:

(1) “Present Knowledge in Nutrition,” 10th ed. 2012;293-306. (2) Arch Intern Med. 1994;154:1586-1595. (3) JAMA Intern Med. 2013;173:1379-1381. (4) Lancet online. 2012 May 17. (5) New Engl J Med. 2014;371:203-212. (6) New Engl J Med. 2011;365:2255-2267. (7) New Engl J Med. 2014;371:288-290. (8) BMJ 2014;349:g4379. (9) J Am Coll Cardiol. 2013;62:1909-1910. (10) European Medicines Agency 2013 Jan. 18.

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 medicalcompassmd.com and/or consult your personal physician.

Triglycerides is a term that most of us recognize. This substance is part of the lipid (cholesterol) profile. However, this may be the extent of our understanding. Compared to the other substances, HDL (“good” cholesterol) and LDL (“bad” cholesterol), triglycerides are not covered much in the lay press and medical research tends to be less robust than for the other components. If I were to use a baseball analogy, triglycerides are the Mets, who get far less attention than their crosstown rivals, the Yankees.

But are triglycerides any less important? It is unclear whether a high triglyceride level is a biomarker for cardiovascular disease – heart disease and stroke – or an independent risk in its own right (1) (2). This debate has been going on for over 30 years. However, this does not mean it is any less important.

What are triglycerides? The most rudimentary explanation is that they are a kind of fat in the blood. Alcohol, sugars and excess calorie consumption may be converted into triglycerides.

Risk factors for high triglycerides include obesity, smoking, a high carbohydrate diet, uncontrolled diabetes, hypothyroidism (underactive thyroid), cirrhosis (liver disease), excessive alcohol consumption and some medications (3).

What levels are normal and what are considered elevated? According to the American Heart Association, optimal levels are <100 mg/dL; however, less than 150 mg/dL is considered within normal range. Borderline triglycerides are 150-199 mg/dL, high levels are 200-499 mg/dL and very high are >500 mg/dL (3).

While medicines that focus on triglycerides, fibrates and niacin, have the ability to lower them significantly, it is questionable whether this reduction results in clinical benefits, like reducing the risk of cardiovascular events. The ACCORD Study, a randomized controlled trial, questioned the effectiveness of medication; when these therapies were added to statins in type 2 diabetes patients, they did not further reduce the risk of cardiovascular disease and events (4). Instead, it seems that lifestyle modifications may be the best way to control triglyceride levels.

Let’s look at the evidence.

Exercise – timing and intensity

If you need a reason to exercise, here is really good one. I frequently see questions pertaining to optimal exercise timing and intensity. Most of the answers are vague, and the research is not specific. However, hold on to your hats, because a recent study may give the timing and intensity answer, at least in terms of triglycerides.

Study results showed that walking a modest distance with alacrity and light weight training approximately an hour after eating (postprandial) reduced triglyceride levels by 72 percent (5). However, if patients did the same workout prior to eating, then postprandial triglycerides were reduced by 25 percent. This is still good, but not as impressive. Participants walked a modest distance of just over one mile (2 kilometers). This was a small pilot study of 10 young healthy adults for a very short duration. The results are intriguing nonetheless, since there are few data that give specifics on optimal amount and timing of exercise.

Exercise trumps calorie restriction

There is good news for those who want to lower their triglycerides: calorie restriction may not the best answer. In other words, you don’t have to torture yourself by cutting calories down to some ridiculously low level to get an effect. We probably should be looking at exercise and carbohydrate intake instead.

In a well-controlled trial, results showed that those who walked and maintained 60 percent of their maximum heart rate, which is a modest level, showed an almost one-third reduction in triglycerides compared to the control group (maintain caloric intake and no exercise expenditure) (6). Those who restricted their calorie intake saw no difference compared to the control. This was a small study of 11 young adult women.

Thus, calorie restriction was trumped by exercise as a way to potentially reduce triglyceride levels.

Carbohydrate reduction not calorie restriction

In addition, when calorie restriction was compared to carbohydrate reduction, results showed that carbohydrate reduction was more effective at lowering triglycerides (7). In this small but well-designed study, patients with nonalcoholic fatty liver disease were randomized to either a lower calorie (1200-1500 kcal/day) or lower carbohydrate (20 g/day) diet. Both groups significantly reduced triglycerides, but the lower carbohydrate group reduced triglycerides by 55 percent versus 28 percent for the lower calorie group. The reason for this difference may have to do with oxidation in the liver and the body as a whole. Both groups lost similar amounts of weight, so weight could not be considered a confounding or complicating factor. However, the weakness of this study was its duration of only two weeks.

Fasting versus nonfasting blood tests

The paradigm has been that, when cholesterol levels are drawn, fasting levels provide a more accurate reading. Except this may not be true.

In a new analysis, fasting may not be necessary when it comes to cholesterol levels. NHANES III data suggests that nonfasting and fasting levels yield similar results related to all-cause mortality and cardiovascular mortality risk. The LDL levels were similarly predictive regardless of whether a patient had fasted or not. The researchers used 4,299 pairs of fasting and nonfasting cholesterol levels. The duration of follow-up was strong, with a mean of 14 years (8).

Why is this relevant? Triglycerides are an intricate part of a cholesterol profile. With regards to stroke risk assessment, nonfasting triglycerides possibly may be more valuable than fasting. In a study involving 13,596 participants, results showed that, as nonfasting triglycerides rose, the risk of stroke also rose significantly (9). Compared to those who had levels below 89 mg/dL (the control), those with 89-176 mg/dL had a 1.3-fold increased risk of cardiovascular events, whereas those within the range of 177-265 mg/dL had a twofold increase, and women in the highest group (>443 mg/dL) had an almost fourfold increase. The results were similar for men, but not quite as robust at the higher end with a threefold increase.

The benefit of nonfasting is that it is more realistic and, according to the authors, also involves remnants of VLDL and chylomicrons, other components of the cholesterol profile that interact with triglycerides and may affect the inner part (endothelium) of the arteries.

What have we learned? Triglycerides need to be discussed, just as we review HDL and LDL levels regularly. Elevated triglycerides may result in heart disease or stroke. The higher the levels, the more likely there will be increased risk of mortality – both all-cause and cardiovascular. Therefore, we ideally should reduce levels to less than 100 mg/dL.

Lifestyle modifications using carbohydrate restriction and modest levels of exercise after a meal may be the way to go to the best results, though the studies are small and need more research. Nonfasting levels may be as important as fasting levels when it comes to triglycerides and the cholesterol profile as a whole; they potentially give a more realistic view of cardiovascular risk, since we don’t live in a vacuum and fast all day.

References:

(1) Circulation. 2011;123:2292-2333. (2) N Engl J Med. 1980;302:1383–1389. (3) nlm.nih.gov. (4) N Engl J Med. 2010;362:1563-1574. (5) Med Sci Sports Exerc. 2013;45(2):245-252. (6) Med Sci Sports Exerc. 2013;45(3):455-461. (7) Am J Clin Nutr. 2011;93(5):1048-1052. (8) Circulation Online. 2014 July 11. (9) JAMA 2008;300:2142-2152.

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 medicalcompassmd.com or consult your personal physician.

Lipoic acid, also known as alpha lipoic acid and thioctic acid, is a noteworthy supplement. I am not a big believer in lots of supplements for several reasons: diet contributes thousands of more nutrients that work symbiotically; in the United States, supplements are not regulated by the FDA, thus there is no official oversight; and research tends to be scant and not well controlled.

So why would I write about lipoic acid? It is a supplement that has scientific data available from randomized controlled trials, which are the gold standard of studies. In Europe, lipoic acid is classified as a drug, unlike the U.S., where it is a supplement (1).

Lipoic acid is an antioxidant, helping to prevent free radical damage to cells and tissues, but also is a chelating agent, potentially removing heavy metals from the body. Lipoic acid is involved in generating energy for cells; it is an important cofactor for the mitochondria, the cell’s powerhouse. It may also boost glutathione production, a powerful antioxidant in the liver (1). We produce small amounts of lipoic acid in our bodies naturally. Lipoic acid may be important in chronic diseases, including Alzheimer’s, multiple sclerosis and diabetic peripheral neuropathy.

Let’s look at the evidence.

Diabetic peripheral neuropathy

Diabetic peripheral neuropathy, or diabetic neuropathy, involves oxidative stress and occurs in up to half the population with diabetes. One in five patients, when diagnosed, will already have peripheral neuropathy. The most common type is distal symmetric polyneuropathy — damage to nerves on both sides of the body in similar locations. It causes burning pain, numbness, weakness and pins and needles in the extremities (2).

The best studies with lipoic acid focus on peripheral neuropathy with diabetes. In a double-blinded, randomized controlled trial (SYDNEY I), results showed that the total treatment score had improved significantly more for those receiving 600 mg of lipoic acid by intravenous therapy compared to the placebo group (3). Also, individual symptoms of numbness, burning pain and prickling significantly improved in the group treated with lipoic acid compared to placebo.

The study involved 120 diabetes patients with stage 2 neuropathy. Its weakness was its duration. It was a very short trial, about three weeks. The author concluded that this therapy would be a good adjunct for those suffering diabetic neuropathy.

In a follow-up to this study (SYDNEY II), the design and the results were the same (4). In other words, in a second double-blinded, placebo-controlled trial, the lipoic acid treatment group showed significantly better results than the placebo group. There were 180 patients with a similarly short duration of five weeks.

Why include this study? There were several important differences. One was that lipoic acid was given in oral supplements, rather than intravenously. Thus, this is a more practical approach. Another difference is that there were three doses tested for lipoic acid: 600 mg, 1200 mg and 1800 mg. Interestingly, all of them had similar efficacy. However, the higher doses had more side effects of nausea, vomiting and vertigo, again without increased effectiveness. This suggests that an oral dose of 600 mg of lipoic acid may help treat diabetic peripheral neuropathy.

Dementia and Alzheimer’s

In a recent randomized, placebo-controlled trial involving Alzheimer’s patients, results were significantly better for lipoic acid (600 mg oral dose) in combination with fish oil, compared to fish oil alone or to placebo (5). The amount of fish oil used was 3 grams daily containing 675 mg of docosahexaenoic acid and 975 mg of eicosapentaenoic acid of the triglyceride formulation. The duration of this pilot study was 12 months with 39 patients, and the primary endpoint was a change in an oxidative stress biomarker, which did not show statistical significance. However, and very importantly, the secondary endpoint was significant: slowing the progression of cognitive and functional decline with the combination of fish oil and lipoic acid. Mini-mental status and instrumental activities of daily living declined less in the combination treatment group. This was encouraging, although we need larger trials.

However, another study showed 900 mg lipoic acid in combination with 800 IU daily of vitamin E (alpha tocopherol strain) and 500 mg of vitamin C actually mildly reduced an oxidative stress biomarker, but had a negative impact on Alzheimer’s disease by increasing cognitive decline on a mini-mental status exam (6). What we don’t know is whether the combination of supplements in this study produced the disappointing effects or if an individual supplement were the cause. It is unclear since the supplements were tested in combination. The study duration was 16 weeks and involved 78 moderate to severe Alzheimer’s patients.

Multiple sclerosis

In a study involving rats, giving them high doses of lipoic acid resulted in slowing of the progression of multiple sclerosis-type disease (7). The mechanism by which this may have occurred involved blocking the number of inflammatory white blood cells allowed to enter the cerebrospinal fluid in the brain and spinal cord by reducing the enzymatic activity of factors such as matrix metalloproteinases.

I know this sounds confusing, but the important point is that this may relate to a human trial with 30 patients that showed reduction in the enzyme MMP (8). Thus, it could potentially slow the progression of multiple sclerosis. This is purely connecting the dots. We need a large-scale trial that looks at clinical outcomes of progression in MS, not just enzyme levels. The oral dose used in this study was 1200 mg to 2400 mg of lipoic acid per day.

Interestingly, the 1200 mg dose used in the human trial was comparable to the high dose that showed slowed progression in the rat study (9). This only whets the appetite and suggests potential.

So, we have lots of data. What do we know? In diabetic neuropathy, 600 mg of oral lipoic acid may be beneficial. However, in Alzheimer’s the jury is still out, although 600 mg of lipoic acid in combination with fish oil has potential to slow the cognitive decline in Alzheimer’s disease. It also may have a role in MS with an oral dose of 1200 mg, though this is early data.

Always discuss the options with your physician before taking a supplement; in the wrong combinations and doses, supplements potentially may be harmful. The good news is that it has a relatively clean safety profile. If you do take lipoic acid, know that food interferes with its absorption, so it should be taken on an empty stomach (1).

References:

(1) lpi.oregonstate.edu. (2) emedicine.
medscape.com. (3) Diabetes Care. 2003;26:770-776. (4) Diabetes Care. 2006;29:2365-2370. (5) J Alzheimers Dis. 2014;38:111-120. (6) Arch Neurol. 2012;69:836-841. (7) J Neuroimmunol. 2002;131:104-114. (8) Mult Scler. 2005;11:159-165. (9) Mult Scler. 2010;16:387-397.

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 medicalcompassmd.com or consult your personal physician.

Fat in the diet is a highly complicated issue. For decades, we have adopted the notion that fat may be the enemy and, therefore, we should eat a low-fat diet. But is this really true? The answer is that we all need fat, but the sources are important.

The cover of Time magazine’s June 23 edition exclaimed in big yellow letters to “Eat Butter. Scientists labeled fat the enemy. Why they were wrong” (1). It also included a picture of a curl of butter, in case you had forgotten what butter looked like. This cover is provocative and tantalizing. However, it does a disservice to the article itself and to the general population who may have seen it.

The article, itself, is well written. Its focus is not mainly on butter, but rather on different types of fats, saturated and unsaturated. The author Bryan Walsh does make salient points, but my objection is mainly that many of these points are buried deep within a five-page, three-column, single-spaced article among comments that are not necessarily substantiated. You have to wade through paragraph after paragraph to get to some these points. Reading the first page is not good enough.

Let’s look at a few studies presented in the article.

Study: Different types of fat — saturated and unsaturated with heart disease.

There was a recent meta-analysis (a group of 72 studies including both observational and randomized controlled trials) that looked at whether different types of fat had an impact on cardiovascular health (2). The results showed that saturated fats, omega-6 polyunsaturated fats and monounsaturated fats were most likely not harmful and that omega-3 polyunsaturated fats were potentially beneficial. However, trans fatty acids were shown to be potentially harmful, with a 17 percent increased risk of cardiovascular disease outcomes such as heart attacks and heart disease.

While this is an interesting study, there are some significant flaws that need to be highlighted.

1. The conclusions in the study don’t match or only partially match. Let me explain. There is a conclusion in the abstract (a synopsis or summary of the study) and a conclusion in the body of the study. The abstract concludes that polyunsaturated fats, including omega-3 fatty acids, are not necessarily beneficial while saturated fat may not be harmful. In the body of the study, the authors conclude that omega-3 fatty acids significantly reduce cardiovascular events. Why is this important? Many physicians are bombarded by studies and may only have time to read the abstract. Thus, this could wrongly influence the physician.

2. The source of fat is never differentiated in the study. In other words, the saturated fats which are deemed harmless may be from foods or supplements that contain both unsaturated fats and saturated fats or from foods that contain only saturated fats. We see benefit in plant-based foods that have multiple types of fats — saturated and unsaturated — such as olive oil, nuts, seeds and avocado. However, most animal fats, like red meat, pork and chicken, contain only saturated fats. The exception is fish, which contains multiple types of fats.

Also, unlike the Time cover story, the study NEVER mentions butter, cheese or red meat. Therefore, the commentary by the press is based on an extrapolation that cannot and should not be made: that eating butter, cheese and red meat maybe harmless and possibly beneficial.

3. The populations of the studies differed at the starts of the different trials. In other words, some were healthy participants, some were high-risk patients and some already had cardiovascular disease. The main thing these studies had in common was that cardiovascular disease outcomes were an endpoint, but it did not have to be the primary, or main, endpoint. Thus, cardiovascular disease outcomes may not have been the main thrust of all the studies that made up the meta-analysis.

4. A meta-analysis by definition is difficult to perform because researchers combine results from studies that were designed and performed differently from one another. In this meta-analysis, the authors combine the results of observational trials that may have used different types of fat intake from food or from supplements. Usually, supplements, like fish oil, involve both saturated and unsaturated fats, and they may have different effects than food.

5. Finally, the study does not tell us what those who ate lower saturated and unsaturated fats ate instead. For example, it compared those who ate high saturated fats to those who ate low saturated fats. What did the group who ate lower saturated fat eat instead of fat? Was it carbohydrates? If so, were they fries, whole grains or sweet potatoes?

The Time cover article goes on to mention the Mediterranean diet and its beneficial effects with heart disease. There was a recent randomized controlled study, the gold standard of studies, called the
PREDIMED trial, with results that showed that participants who ate a Mediterranean diet with added olive oil or mixed nuts had a 30 percent decreased risk of cardiovascular disease than those in the control arm who were advised to follow a “low-fat” diet (3). The Mediterranean diet emphasizes vegetables, fruits, whole intact grains, beans, legumes and fish, as well as olive oil and nuts. This was not a low-fat diet. It contained both saturated and unsaturated fats, including polyunsaturated and monounsaturated fatty acids. The caveat to these results is that the “low-fat” group was not actually able to maintain a low-fat diet, but instead ate more like the standard American diet with no restrictions.

Interestingly, researchers using the same Mediterranean diet study, PREDIMED, showed that higher dietary intake of magnesium reduced the risk of cardiovascular mortality risk by 34 percent (4). They compared those in the highest intake of dietary magnesium with those in the lowest. These participants had a high risk of cardiovascular disease. Foods rich in magnesium include dark green leafy vegetables, such as spinach, as well as nuts, seeds, fish, beans, lentils and avocados.

In conclusion, the sources of fats matter. To run out and eat a cheeseburger, without the bun of course, would be to have misunderstood this article and the flaws in the meta-analysis and to have focused only on the cover of the Time magazine article. The take-home message should be that we need some fats in our diet, but that the sources of these fats are critical. Diet quality is of the utmost importance in reducing disease (5), so put that cheeseburger out of your mind. Many studies have shown that the Mediterranean diet helps reduce the risk of cardiovascular events. For some, this may include the addition of more olive oil and nuts.

References:

(1) Time.com. (2) Ann Intern Med. 2014;160:398-406. (3) N Engl J Med. 2013;368:1279-1290. (4) J Nutr. 2014;144:55-60. (5) Lancet. 2014;383:1999-2007.

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 medicalcompassmd.com or consult your personal physician.

When we refer to diabetes, we think of its complications. It may lead to microvascular maladies that affect vision (retinopathy), the kidneys (nephropathy) and the limbs (peripheral neuropathy), as well as macrovascular diseases such as heart disease and heart attacks. These are important reasons to prevent and treat it.

However, diabetes, in and of itself, is complicated. For example, in the ACCORD trial, we treated diabetes patients aggressively with medication trying to get their HbA1C (three-month sugars) to below 6.0 percent rather than the standard 7.0 percent, because we thought lower would mean fewer complications. According to the results, the patients who were treated more aggressively had a higher risk of mortality (1).

We know that in type 2 diabetes, the first line of therapy beyond lifestyle modifications is metformin. But when that is not enough, we also know that insulin is the most powerful treatment for decreasing glucose, or sugar, levels. But are insulin therapies the best drugs to use? Well, it turns out that they may have more risk of death compared to another drug class, sulfonylureas (e.g., Glucotrol, Amaryl). However, sulfonylureas, along with another drug class, thiazolidinediones (e.g., Avandia, Actos), may increase the risk of fractures. Sulfonylureas and insulin each have also been associated with increased risk of hypoglycemia (low sugar).

Diabetes is also associated with depression. The prevailing thought has been that having diabetes may contribute to depression. However, the association may be related to another common factor, inflammation.

If that were not enough to make your head spin, the Centers for Disease Control reports that one-quarter of patients don’t even know they have diabetes (2). And for people over the age of 20, 33 percent have prediabetes, defined as sugar levels between normal and diabetes, with fasting sugar of 100-125 mg/dl or HbA1C of 5.7-6.4 percent. However, there is good news as it relates to lifestyle modification. Let’s look at the evidence.

Medications: insulin versus
sulfonylurea

Two of the most common medications for the treatment of diabetes, referred to as second-line therapies since they would be used after metformin, are insulin and sulfonylureas. In a recent observational comparative effectiveness trial with patients already on metformin, results showed that  when insulin was added compared to when sulfonylureas were added, there was a 44 percent increased risk of all-cause mortality and a 30 percent increased risk of cardiovascular outcomes including heart attack, stroke or all-cause death (3).

Does this mean we should not use insulin? No. There were limitations to this study. Though it was more sophisticated with its comparative effectiveness design, it was still retrospective, which is not as strong as some other study types and may involve bias. The only conclusion that can be made is that insulin when used with metformin had an association with, but not a link to, significantly negative side effects versus sulfonylureas. These patients were followed for a median of 14 months. We need prospective studies, especially randomized controlled studies. However, the results are intriguing. It makes you think twice before reaching for insulin as a second-line therapy.

Medications: sulfonylureas and thiazolidinediones

Does this mean that we know what to use for second-line therapy? Not necessarily. In a recent study, both sulfonylureas and thiazolidinediones showed a significantly increased risk of fractures. There was a 9 percent increase in fracture risk with sulfonylureas and a 40 percent increased risk with thiazolidinediones when each was compared to metformin (4). The good news is that other drug classes were tested and did not show statistically significant elevated risk occurrences. This was also a retrospective observational study so the same study limitations apply, most importantly, bias and confounding factors.

Depression

To complicate matters further, diabetes and depressive symptoms are associated with each other, but not in the way you might think. According to a recent study, these two maladies may not be a classic chicken-and-egg argument, but rather a common denominator; inflammation may be the culprit that is at least partially responsible for both diseases processes (5).

The researchers found that six biomarkers of inflammation were increased in patients with both diabetes and depressive symptoms. These inflammatory markers include C-reactive protein, tumor necrosis factor alpha, triglycerides, white blood cells, interleukin 1 (IL-1B and IL-1RA) and monocyte chemotactic protein-1. Ultimately, if they are both caused by inflammation to varying degrees, then theoretically if we reduced inflammation it may give us beneficial results for both diseases. This is important, since those with both diseases may have a two times greater likelihood of death, according to the authors. They also note that lifestyle modifications, including diet and exercise, are the best way to reduce inflammation. The study involved 1227 newly diagnosed diabetes patients.

Heart attack

Both men and women with diabetes are at increased risk of heart attacks. However, in a recent meta-analysis (group of 64 studies) involving over 800,000 patients, the results surprisingly show that women with diabetes are at a significantly greater risk of having a heart attack than men (6). In fact, these women were at a 44 percent increased risk of having fatal and nonfatal cardiovascular events compared to their male counterparts. The reason for this, according to the authors, was that women may already be in poorer health before the onset of diabetes. What to do?

Exercise: games

We tell patients to exercise, but many of us know just how difficult it can be to motivate ourselves to do this. Video games may provide the needed spark. In a randomized controlled trial, the gold standard of studies, those who used Wii Fit Plus saw improvements in their diabetes parameters compared to those who were given usual care (7). Results included significant decreases in their HbA1C, fasting blood sugars and weight. These results were seen in just three months. There were also improvements in daily physical activity, quality of life and depressive symptoms that are so commonly associated with diabetes. Family members were also likely to get involved in the Wii with the patient, creating a natural support network. Interestingly, after 12 weeks, those in the control group were then given the Wii Fit Plus and followed for an additional 12 weeks. They saw similar benefits. The authors called this “exergaming.”

Ultimately, we should do a really good job with lifestyle modifications and if that is not enough add metformin, because we know that both have much greater upsides and very few downsides compared to many other diabetes treatments. Exercise can even be fun, as shown by the exergaming study. However, if insulin or other medications are needed, while there are treatment guidelines, it really comes down to a case-by-case decision to be made by the patient and doctor.

References:

(1) N Engl J Med. 2008;358:2545-2559. (2) cdc.gov/diabetes. (3) JAMA. 2014;311:2288-2296. (4) ADA 2014 Scientific Sessions;165-OR. (5) Diabetes Care Online. 2014 May 19. (6) Diabetologia Online. 2014 May. (7) BMC Endocr Disord. 2013;13:57.

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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 medicalcompassmd.com or consult your personal physician.