Nutrition

Little Knowledge, Large Problem: Lack of Nutrition and Obesity Education in Medical Curricula

September 23, 2016

A_doctor_pumps_the_stomach_of_his_obese_seated_patient_while_Wellcome_L0005347By Elissa Driggin

Peer Reviewed

At almost every single one of my medical school interviews, each interviewer, noting my college major in nutritional science, asked some variation of the question, “What should I be eating to stay healthy?” Each time, I was left unsure of whether or not this question was aimed to gauge my ability to hold a conversation in a stressful environment, articulate my thoughts in a logical manner, or fulfill some other mysterious goal of the infamous medical school interview process. Or, could it be possible that a physician truly did not have an idea about what constitutes healthy eating?

It is predictable that more than one medical school lecture will display the chronological progression of the CDC obesity prevalence maps over the years. The colorful representation of the progression to higher percentages of obesity is familiar but still shocking, with the most recent data from 2013 showing that 34.9% of US adults and 17% of US children and adolescents are obese. We are presented with overwhelming evidence that obesity is a risk factor for type 2 diabetes, hypertension, dyslipidemia, osteoarthritis, and sleep apnea. There is no possible way to go through medical school without understanding that obesity is prevalent and contributes to disease risk. But do we ever really learn how to counsel our patients about this issue?

A 2015 article published in the Lancet about the current status of obesity management emphasizes the scarcity of nutrition medical education in US medical schools [1]. Researchers report that, despite 2007 recommendations by the US Association of Medical Colleges to implement education on overweight and obesity management in undergraduate medical curricula, data from a 2009 survey reveal an average of merely 19.6 hours dedicated to the subject throughout the entirety of medical school, with a range of zero to 70 hours. In fact, only 27% of schools meet the minimum requirement of 25 hours established by the Association [2]. One consequence of this lack of education is well demonstrated by a 2005 study that used a cross-sectional medical record review to identify how frequently internal medicine residents documented obesity as a medical problem and how frequently they managed the issue in an outpatient clinic setting. Data showed that residents identified 7.3% of overweight patients (13/178) and 30.9% of their obese patients (76/246).  Even if practitioners identified such patients, it was rare that they intervened: out of the 424 overweight and obese patients in the sample, only 16.5% (70/424) received any form of management for excess weight [3]. Although there was no follow-up as to why, it is likely due to lack of resources, education and confidence in skills.

Another effect of the lack of appropriate education about obesity and its complex etiology is widespread bias among medical students that is likely to impair effective and thorough healthcare delivery. Researchers have identified that medical students in the US are likely to harbor negative biases and stereotypes of obese patients, such as that obese patients are more likely to be noncompliant and less responsive to counseling [4]. However, researchers also demonstrate that, by providing medical students with a more complete education about obesity and associated difficulties, and by providing the opportunity to practice and improve communication skills with educational tools such as standardized patients, biases can be reduced [4, 5]. Other research has shown that, without such focused education, biases are carried through to professional practice, with large samples of practicing physicians across multiple specialties exhibiting implicit and explicit biases against obese patients that have been shown to negatively affect care [6].

While the solution to the problem of lack of medical school education about nutrition and obesity is undoubtedly complex, a commitment to more thorough education is necessary for the effective management of this widespread problem. Physicians themselves have identified inadequate training in areas such as motivational interviewing and nutritional and exercise counseling. Those who did receive education in such areas felt that it was helpful in their practice [7]. While there are many more areas of educational deficit, these areas could be a good place to start.

After a long morning of rounding on an internal medicine inpatient service, it is typical to see groups of senior physicians, residents , and medical students convening around tables of candy, pizza, and various other less-than-nutritious snacks that adorn the tables of the call rooms. Each time, I can’t help but think back to my medical school interviews and realize that the interviewers probably did not have an alternative agenda for their question about how to eat healthy. They, like many of my contemporaries, probably never learned.

Commentary by Dr. Michelle McMacken

Poor nutrition is a key driver of our leading chronic diseases. Most internists spend their days treating diabetes, hypertension, obesity, fatty liver, and coronary artery disease–all of which have a common root in lifestyle and nutrition. The economic and public health costs are staggering. We rely heavily on pills and procedures in part because we lack the skills or the time to offer nutrition and lifestyle counseling, or because we assume that patients won’t make lifestyle changes. But there is abundant, compelling evidence that when patients do make lifestyle changes, the benefits are tremendous.  We owe it to our patients to give them that chance.  Core medical education on nutrition and lifestyle medicine is paramount if we want to address the overwhelming burden of chronic disease.  After all, pills and procedures will treat symptoms, but only lifestyle change can truly treat the cause.

Elissa Driggin is a 3rd year medical student at NYU School of Medicine

Peer reviewed by Michelle McMacken, MD, internal medicine, NYU Langone Medical Center

Image courtesy of Wikimedia Commons

References 

  1. Dietz WH, Baur LA, Hall K, et al. Management of obesity: improvement of health-care training and systems for prevention and care. Lancet. 2015;385(9986):2521-2583. http://www.ncbi.nlm.nih.gov/pubmed/25703112
  2. Adams KM, Kohlmeier M, Zeisel SH. Nutrition education in U.S. medical schools: latest update of a national survey. Acad Med. 2010;85(9):1537–1542. http://www.ncbi.nlm.nih.gov/pubmed/20736683/
  3. Ruser CB, Sanders L, Brescia GR, et al. Identification and management of overweight and obesity by internal medicine residents. J Gen Intern Med. 2005;20(12):1139–1141. http://onlinelibrary.wiley.com/doi/10.1111/j.1525-1497.2006.00561.x/references
  4. O’Brien KS, Puhl RM, Latner JD, Mir AS, Hunter JA. Reducing anti-fat prejudice in preservice health students: a randomized trial. Obesity (Silver Spring). 2010;18(11):2138–2144. http://www.ncbi.nlm.nih.gov/pubmed/20395952
  5. Kushner RF, Zeiss DM, Feinglass JM, Yelen M. An obesity educational intervention for medical students addressing weight bias and communication skills using standardized patients. BMC Med Educ. 2014;14:53. http://www.ncbi.nlm.nih.gov/pubmed/24636594
  6. Foster GD, Wadden TA, Makris AP, et al. Primary care physicians’ attitudes about obesity and its treatment. Obes Res. 2003;11(10):1168–1177. http://www.ncbi.nlm.nih.gov/pubmed/14569041
  7. Bleich SN, Bennett WL, Gudzune KA, Cooper LA. National survey of US primary care physicians’ perspectives about causes of obesity and solutions to improve care. BMJ Open. 2012;2(6). pii:e001871.  http://www.ncbi.nlm.nih.gov/pubmed/23257776/

From The Archives: Metabolic Syndrome: Fact or Myth?

May 22, 2014

Please enjoy this post from the archives dated September 30, 2011

By Vicky Jones, MD

A 40-year-old female presented to her primary care provider with a chief complaint of weight gain over the past year.  She wants to be fully evaluated for any kind of medical disorder that could have caused it.  She has been seen by multiple specialists but no one can give her a “straight diagnosis”.  Their advice is for her to lose weight.  She insists she never had problems with her weight in the past and has no known medical disorders. Her physical exam is significant for a blood pressure of 130/80 and excess fat around her waistline.  Her labs show an elevated serum glucose, an increased total cholesterol and LDL, and a decreased HDL.  Otherwise, she has normal endocrine markers.  Her primary care provider discussed the findings of her workup with her and tells her that she has metabolic syndrome. The patient is grateful for finally finding out what is wrong with her.

Many Americans suffer from the same disorder.  According to the CDC, 34% of American adults have metabolic syndrome.(18)  With such a high prevalence, clinicians have to understand what it is and what it means for their patient.  Researchers and clinicians have been trying to clearly define Metabolic Syndrome since its original inception in the 1980’s.  Thirty years later, it seems the medical community has finally come to a consensus.

During the beginning, Metabolic Syndrome was an explanation for epidemiological trends of patients with concurrent hypertension and hyperglycemia.  A Stanford physician postulated that these conditions were inter-related having one causal pathway related to hyperglycemia, leading to hyperinsulinemia, leading to excess free fatty acids.  This original idea was termed, Syndrome X.[1]  The pathophysiology of Syndrome X was that high levels of free fatty acids induce a state of insulin resistance both in the muscle (glucose uptake) and in the liver (glucose release).  The effect of hyperinsulinemia to increase renal sodium absorption was thought to contribute to hypertension through increased circulating blood volume.

Three years later, the same Stanford physician expanded his definition by discussing how insulin resistance leads to an increase in plasma triglycerides and a decrease in high density lipoprotein-cholesterol concentration, and high blood pressure.  For this reason, he extrapolated that Syndrome X plays an important role in the etiology and clinical course of patients with non-insulin-dependent diabetes, high blood pressure, and coronary heart disease. [2]  The cause- effect relationship interested physicians across disciplines leading to a boom of research related to the etiology, pathophysiology, effects and prognosis of the syndrome.

After further examination, some physicians felt that the syndrome’s original definition was not adequate.  The same population of patients with syndrome X were noted to have a disproportionate prevalence of obesity.  They felt that obesity was likely to play the central role in the syndrome in causing insulin resistance. Research suggested that excess adipose tissue releases free fatty acids and glycerol into the circulation by lipolysis, therefore contributing if not initiating insulin resistance.[4]  Obesity linked with insulin resistance, hypertension and hyperlipidemia became known as the “deadly quartet”.[3]  This addition did not end debate, however.  If anything, it opened more controversy.  Scientists debated whether obesity causes insulin resistance or  vice versa?  Others debated whether obesity or diabetes played any role in the syndrome at all.

The World Health Organization saw the activity and controversy spurred by these theories and in 1998, compiled definitions and described what became recognized as the “metabolic syndrome”: obesity, insulin resistance, dyslipidemia, and hypertension—focusing on insulin resistance as a central tenet.[5]  This was a huge step in validating the syndrome.  However, even after the WHO made the definition official and gave it an ICD code, clinicians continued to question the clinical utility of the definition.

Interdisciplinary meetings further examined research and decided that the clinical utility of describing these patients was to identify a high risk group for cardiovascular disease.[6] Atherosclerosis was shown to be associated with all the parameters of metabolic syndrome. [7] In addition, by this time, scientists had discovered other diseases to be associated with the syndrome as well, such as fatty liver, polycystic ovary syndrome, cholesterol gallstones, sleep apnea, lipodystrophies, and protease-inhibitor therapy for HIV.  Prevention and intervention of the syndrome was viewed as a necessity.

Fast forward to 2005 when the research and discussion up to this point convinced almost all of the major medical associations to agree on the existence and importance of metabolic syndrome.  The American Heart Association in conjunction with the National Heart, Lung, and Blood Institute came up with the most current and widely accepted definition of  metabolic syndrome.[7]  In order to be diagnosed with Metabolic Syndrome, a patient needs 3 of 5 of the following:

– Elevated waist circumference: 102 cm (40 inches) in men, 88 cm (35 inches) in women

– Elevated triglycerides 150 mg/dL (1.7 mmol/L) or on drug treatment for elevated triglycerides

– Reduced HDL-C, < 40 mg/dL (1.03 mmol/L) in men, <50 mg/dL (1.3 mmol/L) in women or on drug treatment for reduced HDL

– Elevated blood pressure 130 mm Hg systolic blood pressure or 85 mm Hg diastolic blood pressure or on antihypertensive drug treatment in a patient with a history of hypertension

– Elevated fasting glucose 100 mg/dL or on drug treatment for elevated fasting glucose

The five criteria listed represent abnormal physical and lab findings that suggest but do not necessarily meet the requirements for a diagnosis of obesity, hyperlipidemia, hypertension, and diabetes, respectively.  The creators seemed to want to catch patients with pre-morbid conditions that increase their risk for morbid conditions. Being able to have a combination of any three allowed for more sensitivity in diagnosis.

Even with the verified definition. there still remained inconsistencies in the pathophysiology behind the disease. Either there is an inherit metabolic disorder (with or without obesity) causing insulin resistance with subsequent release of free fatty acids and pro-inflammatory factors, or it is the adipose tissue in obese people that is insulin resistant, which in and of itself worsens metabolism by muscle and the liver,  also releasing adipokines, a pro-inflammatory byproduct. [8]

Without a set pathophysiology or single pathway of disease, the ability to establish evidence base treatment strategies was stalled.  There were no articles published that suggest any treatment strategies better than those that have already existed for each individual part of the syndrome alone.  For example, if the patient is overweight, he or she should still try behavioral modification to lose weight.  If he or she has hyperlipidemia, diet and pharmacologic therapy is still tried and true.  Glycemic control would not differ between some one with or without metabolic syndrome who has insulin resistance.  It depends on already established parameters such as fasting glucose or glycosylated hemoglobin.

Another flaw exposed after the formation of a widely accepted definition was the fact that there was no established prognostic evidence for the syndrome. Studies showed that there is a higher mortality and cardiovascular risk for patients with metabolic syndrome. [9-11] However, the degree of severity of morbid conditions affected mortality risk to a greater extent rather than whether or not patients met the criterion of metabolic syndrome.  Ten year risk for these patients seemed better predicted by degree of glycemic control or Framingham Risk analysis. [12]  Therefore, questions about clinical utility of the diagnosis lingered.

The World Health Organization met again in 2009 to re-evaluate a consensus statement regarding metabolic syndrome after a decade of shifting meanings and research.  The conclusion was that “While [metabolic syndrome] may be considered useful as an educational concept, it has limited practical utility as a diagnostic or management tool.” [15]  Furthermore the WHO deemed that clinicians should not use this term as a clinical diagnosis and that further research regarding the syndrome would be an inappropriate use of resources.  Even more recently, the proginitor of it all—the Stanford physician that originally created the idea of Syndrome X—published a review article in December of 2010.  In it, he states that “despite the many publications…it is not clear that it is a diagnostic category worth continuing”[16].

What all of this means is that our patient from the case at the beginning does have metabolic syndrome.  Having metabolic syndrome may place this patient at a higher risk for cardiovascular disease and/or death.  It may not change the advice that she receives from her doctors regarding lifestyle changes or medical treatment; however it may appropriately target her for aggressive intervention.

In conclusion, Metabolic Syndrome has not proven to be as solid of a “disease” as it was once theorized.  It describes a set of pre-morbid conditions without a unifying underlying disease, making it fall shy of the official definition of a “syndrome”.[17] And it is important to understand that the international community does not view it as a valid diagnosis.  Although, physicians may still use the terminology as a way to describe a patient or a way to closely watch patients at higher risk for developing co-morbidities.  In this way, it may still prove to have clinical utility as a descriptor.

Dr. Vicky Jones is a 3rd year resident at NYU Langone Medical Center

Image courtesy of Wikimedia Commons

References

  1. Reaven G.M.:  Banting lecture 1988. Role of insulin resistance in human disease.  Diabetes 37. (12): 1595-1607.1988.
  2. Reaven GM. Role of insulin resistance in human disease (syndrome X): an expanded definition. Annu Rev Med. 1993;44:121-31.
  3. Kaplan NM. The deadly quartet. Upper-body obesity, glucose intolerance, hypertriglyceridemia, and hypertension. Arch Intern Med. 1989; 149:1514 –1520
  4. “Obesity” Goldman: Cecil Medicine, 23rd ed. 2007.
  5. Gallagher E G, LeRoith D, Karnieli E.  The Metabolic Syndrome – from insulin resistance to Obesity and Diabetes.   Endocrinol Metab Clin N Am 37 (2008) 559–579.
  6. Grundy S, Cleeman J, Daniels S, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation 2005;112(17):2735–-52.  http://circ.ahajournals.org/content/112/17/2735.full
  7. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143–3421. Circulation. 2002;106:3143–3421.
  8. Trayhurn P, Wood IS. Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr. 2004;92:347–355.  http://journals.cambridge.org/download.php?file=%2FBJN%2FBJN92_03%2FS0007114504001795a.pdf&code=560b41b8c0825a15a8274c4fdfabca59
  9. Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M, Taskinen MR, Groop L. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 2001;24:683– 689.
  10. Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, Salonen JT. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA. 2002;288: 2709–2716.
  11. Sattar N, Gaw A, Scherbakova O, Ford I, O’Reilly DS, Haffner SM, Isles C, Macfarlane PW, Packard CJ, Cobbe SM, Shepherd J. Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study. Circulation. 2003 Jul 29;108(4):414-9. Epub 2003 Jul 14.
  12. McNeill AM, Rosamond WD, Girman CJ, Golden SH, Schmidt MI, East HE, Ballantyne CM, Heiss G. The metabolic syndrome and 11-year risk of incident cardiovascular disease in the atherosclerosis risk in communities study. Diabetes Care. 2005;28:385–390.
  13. Solymoss BC, Bourassa MG, Lesperance J, Levesque S, Marcil M, Varga S, Campeau L. Incidence and clinical characteristics of the metabolic syndrome in patients with coronary artery disease. Coron Artery Dis. 2003;14:207–212.
  14. Turhan H, Yasar AS, Basar N, Bicer A, Erbay AR, Yetkin E. High prevalence of metabolic syndrome among young women with premature coronary artery disease. Coron Artery Dis. 2005;16:37– 40.
  15. Simmons RK, Alberti KG, Gale EA, Colagiuri S, Tuomilehto J, Qiao Q, Ramachandran A, Tajima N, Brajkovich Mirchov I, Ben-Nakhi A, Reaven G, Hama Sambo B, Mendis S, Roglic G. The metabolic syndrome: useful concept or clinical tool? Report of a WHO Expert Consultation. Diabetologia. 2010 Apr;53(4):600-5. Epub 2009 Dec 11.
  16. Reaven GM. The metabolic syndrome: time to get off the merry-go-round? (Review) J Intern Med 2011; 269: 127–136.  http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2010.02325.x/abstract
  17. “Syndrome.” Oxford English Dictionary. 2nd edition. 1989.
  18. Ervin RB. Prevalence of Metabolic Syndrome Among Adults 20 Years of Age and Over, by Sex, Age, Race and Ethnicity, and Body Mass Index: United States, 2003–2006. National Health Statistics Reports. Number 13.  May 5, 2009. http://www.ncbi.nlm.nih.gov/pubmed/19634296

 

MSG: Can an Amino Acid Really Be Harmful?

April 30, 2014

By Michael Lee, MD

Peer Reviewed

The human taste bud has become increasingly accustomed to the Japanese invention of the early 20th century: monosodium glutamate, better known as MSG. Its basic component, glutamate, is a non-essential amino acid found in many naturally occurring food sources. This universally consumed food additive has historically garnered much attention for its potential threat to human health. To best understand how an amino acid has amassed such a tarnished reputation, we must first consider the history of its discovery and popularization.

Glutamate was first isolated in 1908 by a Japanese chemist Ikeda Kikunae from konbu seaweed stock, a type of broth commonly used in Japanese cuisine. Denoting the unique savory flavor of glutamate, Kikunae coined the term umami, a Japanese colloquialism for “tasty.” Soon after its discovery, MSG became mass-produced in Japan and gained its status as a predominant flavor enhancer in Japanese households [1].

Yet humans enjoyed the umami flavor long before the first commercialization of MSG [2]. Glutamate is tasteless when a part of an intact protein, but the process of heating, ripening, aging or fermenting hydrolyzes glutamic acid into its free form and creates the savory umami flavor by activating G-protein coupled receptors in the tongue [3]. The umami flavor of the free glutamic acid is a key component that enhances tastes of many naturally occurring flavorful foods, including seafood, meats and vegetables. For example, free glutamate accumulates in ripened tomatoes and cured ham, creating their characteristic tastes. Contents of glutamate and other amino acids are reliable indicators for the taste and texture of cheese in the manufacturing process[2].

Historically, the nationwide acceptance of MSG symbolized a triumph of post-Victorian science in the 20th century Japan. Much like the German invention of beef extract used to enhance meals for German soldiers, Japanese believed the widespread use of MSG was an illustration of ways in which scientific advancement benefited the health of Japanese citizens. At restaurants and homes, MSG allowed convenient and efficient food preparation through reliable synthesis of the umami flavor [1].

This welcoming stance on MSG was replicated in other Asian countries and later in the United States. As a result of rapid industrialization and technological advancement of the 1920’s, an increasing number of Americans consumed MSG-containing ready-made canned and frozen foods. American canned soup producers like the Campbell’s Soup Company were a major importer of MSG. The umami flavor gained further popularity in the 1930’s with the popularization of Chinese restaurants that routinely incorporated MSG into their cooking. The U.S. military during the post-World War II era also utilized MSG in an effort to maintain morale of the troops with tasteful food [1].

The wide acceptance of glutamate in the U.S. began dwindling in the 1960’s as American public’s concern for its safety came into the spotlight, ignited by publicized discussions of potential dangers of other food additives like cyclamate and saccharine [1]. In 1968, the New England Journal of Medicine published the first article in history questioning the safety of MSG. In a letter to the journal editors, a Chinese-American doctor from Maryland named Robert Kwok described a case series of generalized weakness, palpitations and neck numbness radiating to the back and the upper extremities following ingestion of northern Chinese food [4]. Kwok included MSG in a list of potential culprits, and this constellation of symptoms became known as “Chinese Restaurant Syndrome” [1]. Decades later, in 1995, the Federation of American Societies for Experimental Biology released a statement, renaming the syndrome “monosodium glutamate (MSG) symptom complex” and expanding associated symptoms to include chest pain, facial pressure, headache and bronchospasm [3].

Soon after the initial publication of Kwok’s letter, the potential neurotoxic effect of MSG came to the forefront of public attention when researcher John Olney demonstrated that subcutaneous MSG injections cause acute neuronal necrosis in the developing brains of newborn mice [5]. In 1969, this finding led Jean Mayer, the chair of the White House Conference on Food, Nutrition and Health, to recommend against the use of MSG in baby foods [1]. The result of Olney’s experiment was later reproduced in other animal models, including rabbits and Rhesus monkeys [6].

Despite these early findings from animal studies, more recent evidence demonstrates that MSG does not confer neurotoxicity in humans. Mammals, including humans, are able to tolerate much higher doses of oral glutamate compared to other animals. This apparent immunity to the neurotoxic effect of glutamate is in part due to controlled rates of intestinal amino acid absorption and hepatic metabolism of glutamate into alpha-ketoglutarate. Furthermore, the concentration of glutamate in human milk is much higher (127 micromole/dL) than that in mice (5.7 micromole/dL) or Rhesus monkeys (31.4 micromole/dL) [6]. This difference in milk glutamate concentrations indicates that humans can naturally tolerate large amounts of oral glutamate intake, as demonstrated by several clinical studies. In one study, oral boluses of MSG given to human subjects at doses of 150 mg/kg (approx. 10g of MSG for an average adult) did not significantly increase serum glutamate levels [7]. Considering that the estimated daily intake of MSG is 1.2-1.7 g in countries like Korea and Japan, where MSG consumption per capita is the highest, ingestion of MSG in quantities large enough to alter serum MSG levels seems unlikely [8]. Side effects, namely nausea, limit human tolerability of MSG to amounts less than 60 mg/kg and deter humans from reaching the effective median dose of MSG (500 mg/kg) known to produce hypothalamic lesions in neonatal mice [6].

Since the early 1970’s, six small double-blind placebo-controlled trials examining the validity of the MSG symptom complex have been published. These studies involved oral challenges of placebo and MSG while monitoring the participants for MSG-related symptoms [9-14]. While all trials were small in size, the largest with only 61 subjects, four of the six trials showed no relationship between MSG and the symptom complex [9-11, 13]. It was also noted that positive correlation between MSG ingestion and the symptom complex was mitigated when MSG was consumed with food rather than alone [12, 13].

In 2000, Geha and colleagues published the largest study to date on the MSG symptom complex, involving 103 self-identified participants who reported history of experiencing MSG-related side effects. In this multi-staged, double-blind, placebo-controlled trial, 86 of the 103 subjects developed two or more MSG-associated symptoms in response to MSG, placebo or both. Of the 86 individuals, 69 were then randomly challenged with 1.25 g, 2.5 g or 5 g of MSG or placebo. Although a positive dose-response relationship was seen between MSG and its associated symptoms, the observed clinical manifestations were relatively benign conditions such as headache or transient numbness/tingling sensations. More importantly, none of these subjective symptoms were reproducible, and their incidence decreased when MSG was administered with food [15].

Of the many symptoms thought to be linked to MSG exposure, MSG-induced asthma exacerbation is of particular concern and has been the subject of multiple clinical trials over the past three decades. The first report of bronchospasm resulting from MSG exposure was in a 1981 case-series of two women, who experienced asthma attacks after eating Chinese food. Asthma exacerbation was reproduced in these two subjects following 2.5 g oral MSG challenges [16]. This initial report was followed by two single-blind studies, both of which claimed decreased peak expiratory flow rates (PEFR) in response to oral MSG challenges [17, 18]. Despite the positive findings, these studies were criticized for poor study design, including discontinuation of home anti-asthmatic medications [3]. Contrary to claims of MSG-induced asthma, several double-blind placebo-controlled studies failed to demonstrate a significant association between MSG and asthma exacerbation [19, 20]. In the case of two double-blind placebo-controlled trials that did show MSG-induced reduction in FEV1, the results were not reproducible in subsequent trials [21, 22].

Although rare cases of MSG-induced symptoms cannot be entirely dismissed, numerous studies show neither reproducible correlation nor causality between MSG and neurotoxicity, asthma exacerbation or the MSG symptom complex. Professional societies agree that there is not convincing clinical evidence to support validity of the MSG symptom complex. In 1988, the Joint FAO (Food and Agriculture Association of the United Nations)/WHO (World Health Organization) Expert Committee on Food Additives recognized that dietary glutamate exposure does not pose a threat to human health and relegated glutamate to the “acceptable daily intake (ADI) not specified” category [23]. In 2003, the International Food Information Council Foundation also endorsed glutamate as safe for the general population, including pregnant and lactating women [2].

Despite the negative speculations surrounding the safety of MSG, new research suggests it indeed may be beneficial to human health. Recent animal studies identified glutamate receptors in the gastric mucosa that can trigger afferent vagal stimulation to promote digestion and nutrient metabolism [24, 25]. MSG may also motivate food ingestion in an elderly population that often suffers from poor nutritional intake [26]. In fact, some groups purport that MSG use allows reduction in fat and sodium content of food without compromising palatability, thereby inferring a potential role of MSG in the management and prevention of cardiovascular comorbidities [2]. Even with these emerging acclamatory data, the future of MSG will be dictated largely by any shifts in the public view of this controversial compound.

Dr. Michael Lee is a 1st year resident at NYU Langone Medical Center

Peer reviewed by Cara Litvin, MD, Editor-At-Large, Clinical Correlations

Image courtesy of Wikimedia Commons

References

1. Sand J. A Short History of MSG: Good Science, Bad Science, and Taste Cultures. Gastronomica. 2005;5(4):38-49. http://www.gastronomica.org/fall-2005/

2. Jinap S, Hajeb P. Glutamate. Its Applications in Food and Contribution to Health. Appetite. 2010 Aug;55(1):1-10. Epub 2010 May 12. http://www.sciencedirect.com.ezproxy.med.nyu.edu/science/article/pii/S0195666310003089

3. Williams AN, Woessner KM. Monosodium Glutamate ‘Allergy’: Menace or Myth? Clin Exp Allergy. 2009 May;39(5):640-6. Epub 2009 Apr 6. http://www.ncbi.nlm.nih.gov/pubmed/19389112

4. Kwok R. Chinese-Restaurant Syndrome. N Engl J Med. 1968 Apr; 278(14):796. http://www.nejm.org/doi/full/10.1056/NEJM196804042781419

5. Olney JW. Brain lesions, Obesity, and Other Disturbances in Mice Treated with Monosodium Glutamate. Science. 1969 May 9;164(3880):719-21. http://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=5778021

6. Walker R, Lupien JR. The Safety Evaluation of Monosodium Glutamate. J Nutr. 2000 Apr;130(4S Suppl):1049S-52S. http://jn.nutrition.org/content/130/4/1049.long

7. Tung TC, Tung TS. Serum Free Amino Acid Levels after Oral Glutamate Intake in Infant and Adult Humans. Nutr Rep Int. 1980; 22:431-443.

8. Biesalski HK, Bässler KH, Diehl JF, Erbersdobler HF, Fürst P, Hammes W. Na-Glutamat. Akt Ernahr Med. 1997; 22:169–178.

9. Morselli PL, Garattini S. Monosodium Glutamate and the Chinese Restaurant Syndrome. Nature. 1970 Aug 8;227(5258):611-2. http://www.nature.com/nature/journal/v227/n5258/abs/227611a0.html

10. Zanda G, Franciosi P, Tognoni G, et al. A Double Blind Study on the Effects of Monosodium Glutamate in Man. Biomedicine. 1973 May 20;19(5):202-4. http://www.ncbi.nlm.nih.gov/pubmed/4577013

11. Rosenblum I, Bradley JD, Coulston F. Single and Double Blind Studies with Oral Monosodium Glutamate in Man. Toxicol Appl Pharmacol. 1971 Feb;18(2):367-73. http://www.ncbi.nlm.nih.gov/pubmed/4936399

12. Kenney RA, Tidball CS. Human Susceptibility to Oral Monosodium L-Glutamate. Am J Clin Nutr. 1972 Feb;25(2):140-6. http://ajcn.nutrition.org/content/25/2/140.long

13. Tarasoff L, Kelly MF. Monosodium L-Glutamate: a Double-Blind Study and Review. Food Chem Toxicol. 1993 Dec;31(12):1019-35. http://www.ncbi.nlm.nih.gov/pubmed/8282275

14. Yang WH, Drouin MA, Herbert M, Mao Y, Karsh J. The Monosodium Glutamate Symptom Complex: Assessment in a Double-Blind, Placebo-Controlled, Randomized Study. J Allergy Clin Immunol. 1997 Jun;99(6 Pt 1):757-62. http://www.ncbi.nlm.nih.gov/pubmed/9215242

15. Geha RS, Beiser A, Ren C, et al. Review of Alleged Reaction to Monosodium Glutamate and Outcome of a Multicenter Double-Blind Placebo-Controlled Study. J Nutr. 2000 Apr;130(4S Suppl):1058S-62S. http://jn.nutrition.org/content/130/4/1058.long

16. Allen DH, Baker GJ. Chinese-Restaurant Asthma. N Engl J Med. 1981; 305:1154-1155. http://www.nejm.org/doi/full/10.1056/NEJM198111053051915

17. Allen DH, Delohery J, Baker G, et al. Monosodium L-Glutamate-Induced Asthma. J Allergy Clin Immunol. 1987 Oct;80(4):530-7. http://www.ncbi.nlm.nih.gov/pubmed/3312372

18. Moneret-Vautrin DA. Monosodium Glutamate-Induced Asthma: Study of the Potential Risk of 30 Asthmatics and Review of the Literature. Allerg Immunol (Paris). 1987 Jan;19(1):29-35. http://www.ncbi.nlm.nih.gov/pubmed/3331265

19. Schwartzstein RM, Kelleher M, Weinberger SE, Weiss JW, Drazen JM. Airway Effects of Monosodium Glutamate in Subjects with Chronic Stable Asthma. J Asthma. 1987;24(3):167-72. http://www.ncbi.nlm.nih.gov/pubmed/3505530

20. Woods RK, Weiner JM, Thien F, Abramson M, Walters EH. The Effects of Monosodium Glutamate in Adults with Asthma Who Perceive Themselves to Be Monosodium Glutamate-Intolerant. J Allergy Clin Immunol. 1998 Jun;101(6 Pt 1):762-71. http://www.ncbi.nlm.nih.gov/pubmed/9648703

21. Germano P, Cohen SG, Hahn B, Metcalfe DD. An Evaluation of Clinical Reactions to Monosodium Glutamate (MSG) in Asthmatics, Using a Blinded Placebo-Controlled Challenge [abstract]. J Allergy Clin Immunol. 1991; 87:177. http://www.sciencedirect.com/science/article/pii/009167499191438Y

22. Woessner KM, Simon RA, Stevenson DD. Monosodium Glutamate Sensitivity in Asthma. J Allergy Clin Immunol. 1999 Aug;104(2 Pt 1):305-10. http://www.ncbi.nlm.nih.gov/pubmed/10452749

23. Joint FAO/WHO Expert Committee on Food Additives (JECFA): L-Glutamic Acid and Its Ammonium, Calcium, Monosodium and Potassium Salts. Toxicological Evaluation of Certain Food Additives and Contaminants 1988:97–161. New York Cambridge University Press.

24. Uneyama H, Niijima A, San Gabriel A, Torii K. Luminal Amino Acid Sensing in the Rat Gastric Mucosa. Am J Physiol Gastrointest Liver Physiol. 2006 Dec;291(6):G1163-70. Epub 2006 Jun 29. http://ajpgi.physiology.org/content/291/6/G1163

25. Kondoh T, Mallick HN, Torii K. Activation of the Gut-Brain Axis by Dietary Glutamate and Physiologic Significance in Energy Homeostasis. Am J Clin Nutr. 2009 Sep;90(3):832S-837S. Epub 2009 Jul 8. http://ajcn.nutrition.org/content/90/3/832S.long

26. Schiffman SS, Warwick ZS. Effect of Flavor Enhancement of Foods for the Elderly on Nutritional Status: Food Intake, Biochemical Indices, and Anthropometric Measures. Physiol Behav. 1993 Feb;53(2):395-402. http://www.ncbi.nlm.nih.gov/pubmed/?term=8446704

The Yolk Or The Egg

February 27, 2014

By Nicole A. Lamparello, MD and Molly Somberg, MD, MPA

Peer Reviewed

You hear it wherever you eat, whether at the deli ordering a breakfast sandwich or at the diner for Sunday brunch, “Egg whites only, please.” For the last decade, there has been a strong movement toward avoiding egg yolks; instead people are opting for only the ‘healthier’ egg white when ordering or cooking their breakfast.

However, are egg whites truly ‘healthier’ than eating whole eggs? What is the basis for this decision being made at breakfast tables throughout the country?

The ‘egg-white movement’ surfaced out of a concern for the high cholesterol level found in egg yolks. An egg yolk contains 185 mg cholesterol, which is approximately 66% of the daily-recommended value of cholesterol [1]. Elevated low-density lipoprotein cholesterol (LDL) has been identified as a major risk factor for coronary artery disease (CAD). According to the lipid hypothesis, elevated serum cholesterol can penetrate the arterial wall of coronary arteries, becoming trapped, and then circulating white blood cells engulf cholesterol, resulting in the accumulation of lipid-laden white blood cells. This sets forth a series of events, which causes local injury, cell death, calcification, and the development of a ‘fibrous cap’ over the atherosclerotic plaque. If the cap ruptures, blood clots and blocks the artery, causing a myocardial infarction (MI) [2].

Given this presumptive mechanism of cholesterol consumption leading to CAD, dietary guidelines to prevent heart disease emphasize the reduction in dietary cholesterol to less than 300 mg per day [3]. Several studies have found evidence of this association between dietary cholesterol consumption and CHD. In a study of 514 Western Australian Aborigines, a 2.6-fold increased risk of CHD was reported in individuals consuming 2+ vs. < 2 eggs per week after 14 years [4].

In another large study of over 10,000 men and women in the UK, Mann et al. found an association between egg consumption and increased mortality. After adjustment for age, gender, smoking status, and socioeconomic status, the authors found that consuming 1-5 eggs per week led to a statistically significant death rate ratio of 128, which means that there was a 28% increase in the death rate in this sub-population of individuals consuming between 1 to 5 eggs per week versus the sub-population who consumed less than 1 egg per week on average. However, it should be noted that this was a study of health individuals in which the mortality from CAD was less than half of what would be expected in the general population in the UK at the time [5].

Despite this strong evidence of an association between egg consumption and CAD, several recent studies have challenged the notion that egg consumption carries an increased risk of CAD. The Health Professionals Follow-up Study and the Nurses’ Health Study examined approximately 118,000 men and women without cardiovascular disease, diabetes, hypercholesterolemia, or cancer at study onset. After adjustment for age, smoking status, and other potential CAD risk factors, the authors found that there was no difference in the relative risk for CAD between those who consumed <1 egg/week and those who ate >1 egg/day [6]. However, in subgroup analyses, higher egg consumption appeared to be associated with increased risk of CAD among diabetics. The authors hypothesize that this may be because cholesterol consumption in diabetics leads to a shift in a diabetic’s lipid profile towards smaller, denser LDL particles, which are thought to be more atherogenic. Finally, in the 2008 Physicians’ Health Study, 21,327 participants were followed for 20 years. Results supported the previous studies and showed no evidence of an overall significant association between egg consumption and incident MI or stroke [7].

There are no studies comparing the health of people who eat whole eggs to those who simply eat egg whites, however, it should be noted that the yolk contains the most nutrients in the egg [1]. The yolk contains the fat-soluble vitamins A, E, D and K. Specifically, the yolk contains 41 IU of vitamin D, a vitamin that approximately 25-75% of Americans are deficient in [8]. Vitamin D is crucial for bone and muscle health and immune system function. The yolk is also full of minerals including: calcium, copper, iron, phosphorus, zinc, thiamin, vitamin B5, B6, B12 and folate [1]. Egg yolks are also an excellent source of carotenoids, particularly lutein and zeaxanthin. Carotenoids accumulate in the back of the eye and appear to protect against age-related macular degeneration [9]. Finally, egg yolks contain docosahexaenoic acid (DHA), a long-chain omega-3 fatty acid, and arachidonic acid, a long-chain omega-6 fatty acid. Preliminary evidence shows that these fatty acids are anti-inflammatory, cardio-protective and may even have an anti-cancer effect [10].

On the other hand, egg whites contain far fewer nutrients, although the white is useful as an added source of magnesium, sodium, and niacin [1]. Egg whites are often praised for its high protein content, however, the yolk is actually responsible for half of the protein in the egg. While egg whites are low in calories (~17 calories/egg), it seems the beneficial effects of the yolk outweigh the cost of a 59-calorie yolk. .

So, the question remains, “How should I order my omelet?”

Missing out on the egg yolk means missing out on the nutrition in your breakfast. Although the yolk is high in cholesterol, most studies agree that consumption of up to one egg per week is unlikely to have a substantial impact on the risk of CAD or stroke among healthy adults. However, be careful when ordering an omelet, as it can have 3 or more eggs, and these larger portions may mean excess calories and weight gain, thus the benefits of the egg yolk may be lost. Also, since the data is still inconsistent, dietary suggestions for patients with cardiovascular disease, diabetes, severe risk factors, or a family history of premature atherosclerosis, should err on the side of caution. Much like other foods, when eaten in moderation, eggs, the white and the yolk, are a safe, nutrient-rich, and delicious source of fuel for the body.

Dr. Nicole Lamparello is a first year radiology resident at Beth Israel Hospital and Dr. Molly Somberg, MPA is a first year internal medicine resident at NYU Langone Medical Center.

Peer reviewed by Melanie Jay, MD, Internal Medicine, NYU Langone Medical Center

Image courtesy of Wikimedia Commons

References:

1. USDA Nutrient Database for Standard Reference, Release 15. United States Department of Agriculture Research Service website: http://www.ars.usda.gov.

2. Steinberg D. Thematic review series: the pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy, part V: the discovery of the statins and the end of the controversy. J. Lipid Res. 2006; 47 (7): 1339–51.  http://www.ncbi.nlm.nih.gov/pubmed/16585781

3. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486–97.

4. Burke V, Zhao Y, Lee AH, et al. Health-related behaviours as predictors of mortality and morbidity in Australian Aborigines. Prev Med. 2007; 44:135–42.

5. Mann JI, Appleby PN, Key TJ, Thorogood M. Dietary determinants of ischaemic heart disease in health conscious individuals. Heart. 1997; 78:450–5.  http://www.ncbi.nlm.nih.gov/pubmed/9415002

6. Hu FB, Stampfer MJ, Rimm, EB et al. A Prospective Study of Egg Consumption and Risk of Cardiovascular Disease in Men and Women. JAMA. 1999; 281(15):1387-1394. http://www.ncbi.nlm.nih.gov/pubmed/10217054

7. Djoussé L, Gaziano JM. Egg consumption in relation to cardiovascular disease and mortality: the Physicians’ Health Study. Am J Clin Nutr. 2008; 87(4):964-9.  http://ajcn.nutrition.org/content/87/4/964.full

8. Hanley DA, Davison KS. Vitamin D insufficiency in North America. J Nutr. 2005; 135(2):332-7.  http://jn.nutrition.org/content/135/2/332.long

9. Handleman, G. J., Dratz, E. A., Reay, C., van Kuijk, F.J.G.M. Carotenoids in the human macula and whole retina. Invest. Opthamol. Vis. Sci. 1998; 29:850-855.

10. Herron KL and Fernandez ML. Are the Current Dietary Guidelines Regarding Egg Consumption Appropriate? J. Nut  http://jn.nutrition.org/content/134/1/187.long

 

From The Archives – The Hangover: Pathophysiology and Treatment of an Alcohol-Induced Hangover

January 16, 2014

Please enjoy this post from the archives, dated May 27, 2011

By Anthony Tolisano

Faculty Peer Reviewed

The sunlight forces its way into your eyes, stabbing at your cortex. Suddenly, a wave of nausea and diarrhea grips your stomach, threatening to evacuate its contents. You rush to the bathroom, tripping over the clothes that speckle your apartment. Your heart pounds inside your chest and your hands shake ever so subtly. Your mind is in a fog and the details of last night’s party are a blur. Sound familiar?

If you’re anything like the millions of people who have ever drunk too much alcohol, you’ll immediately recognize the sordid signs of a hangover. It’s a condition that is well recognized yet poorly understood. Descriptions abound in pop culture and literature, saturating the public consciousness. Yet, a great deal of scientific research has had only limited success in explaining its pathophysiology.

The basic concept is simple. A hangover is secondary to binge drinking, the consumption of an excessive amount of alcohol in a relatively short time period. The National Institute of Alcohol Abuse and Alcoholism defines binge drinking as a rise in blood alcohol content (BAC) to greater than or equal to 0.08% within two hours, or more simply, the consumption of at least four (for women) or five (for men) alcoholic beverages in a single drinking session.[1] Of note, most people who binge drink consume far more than 4-5 drinks, imbibing an average of eight per night. [2] Binge drinking is extremely common, especially among young adults, and remains the leading cause of death each year among college-aged students in the US, [3] with similar worldwide rates of problematic alcohol use across Europe, South America, and Australia.[4] The dangers of consuming too much alcohol are obvious. Among other things, motor vehicle accidents, sexual assaults, and violence are more common among the acutely intoxicated. [5] A hangover, however, is largely regarded as an annoyance. It is defined as that which occurs after the acute intoxication has subsided, reaching its greatest intensity as the BAC approaches zero. It lasts for up to 24 hours and consists of a myriad of signs and symptoms, from constitutional (fatigue and malaise) and gastrointestinal (loss of appetite, diarrhea, and nausea), to nociceptive (headache and myalgias) and autonomic (tachycardia and tremor). Sleep disturbances, including increased slow-wave and decreased REM sleep, and neurocognitive symptoms, such as decreased attention and memory problems, are also common.[6] Furthermore, the impairment of one’s psychomotor performance can be substantial. In fact, if you think sobering up is sufficient for safely driving home, you may be wrong. Studies have shown that individuals who suffer from hangover symptoms have a decreased ability to operate a motor vehicle. [7], [8] Combined with the loss of work days and decreased productivity from hangovers, perhaps this annoying day-after affair isn’t so benign after all.

So what is the pathophysiological explanation for a hangover? If a hangover is secondary to the clearance of ethanol from the body (when BAC is equal to zero), isn’t it the same phenomenon as acute alcohol withdrawal? The answer, quite simply, is no. Alcohol withdrawal is secondary to the development of physiological alcohol dependence over the course of many drinking episodes, whereas the hangover occurs after one night of drinking and does not require alcohol dependence. Another possibility is that that a hangover may be the result of the direct effects of last night’s extracurricular activities. That is, a hangover may be the lasting effects of electrolyte imbalances, hypoglycemia, and dehydration, which persist longer than the ethanol itself. Unfortunately, studies have shown little correlation between hangover symptoms and serum electrolytes, blood glucose, or markers of dehydration such as antidiuretic hormone and renin. A similar argument has been made for acetaldehyde, a metabolic breakdown product of ethanol that has vasodilatory and gastrointestinal effects on the body. Again, limited evidence has been found linking acetaldehyde levels with hangover severity.[9] Perhaps understanding the effect of alcohol consumption on the immune system will elucidate the underlying cause of the hangover. A number of studies have shown that following a night of heavy drinking there is an upregulation of cytokines and prostaglandins. Specifically, increased plasma levels of interleukin-10, interleukin-12, and interferon-gamma were measured in individuals suffering from hangover symptoms long after their last drink. Prostaglandin E2, thromboxane B2, and C-reactive protein were similarly increased. Most importantly, the serum levels of these inflammatory markers were directly related to the degree of hangover symptoms.[10] This association has been supported by evidence that treatment with cyclooxygenase inhibitors leads to a decrease in these inflammatory factors and a subsequent decrease in hangover symptoms.[11] Unfortunately, this finding has not been regularly repeated in well-designed studies.

While the exact biological basis of a hangover may remain somewhat of a mystery, there is good evidence that certain factors exacerbate hangover symptoms. Certainly, sleep deprivation and the simultaneous consumption of other psychoactive substances worsen hangover symptoms. Perhaps less intuitively, so does the type of alcohol, even if two drinks contain the same alcohol content by volume. Simply put, darker liquors generally cause worse hangover symptoms. It is thought that this is due to so-called congeners, byproducts of the fermentation process related to the different casks and grains used. For example, amber-colored bourbon has a congener level of 37 times that of vodka, causing worse hangover symptoms than its clearer cousin.[12] At the end of the day, hangovers are unpleasant, to say the least. While a Google search for hangover remedies reveals thousands of hits for reportedly “clinically-proven” cures, there are really no good options. No evidence supports B vitamins, tomato juice, or fatty foods.[13] Other, more colorful options, such as the use of artichoke extract, reveal no difference between the study group and the control group.[14] The one bright spot? Prickly pear (Opuntia ficus indica) extract has been shown to decrease the inflammation associated with hangovers and the subsequent incidence of nausea, dry mouth, and anorexia.[15] As you may have suspected, however, the most important factor in preventing a hangover remains abstinence or moderation. In other words, avoid binge drinking entirely. Alternate alcoholic and non-alcoholic beverages or spread your alcohol consumption over a longer period of time.

Anthony Tolisano is a 3rd year medical student at NYU Langone Medical Center

Peer reviewed by Barbara Porter, section editor, Clinical Correlations

Image courtesy of Google Images

References:

1. National Institute of Alcohol Abuse and Alcoholism. NIAAA council approves definition of binge drinking. NIAAA Newsletter 2004; No. 3, p. 3. Available at http://pubs.niaaa.nih.gov/ /Newsletter/winter2004/Newsletter_Number3.htm#council. Accessed November 17, 2010

2. Naimi TS, Nelson DE, Brewer RD. The intensity of binge alcohol consumption among U.S. adults. Am J Prev Med. 2010;38(2):201-207. http://www.sciencedirect.com/science/article/pii/S0749379709007582

3. Boyd CJ, McCabe SE, Morales M. College students’ alcohol use: a critical review. Annu Rev Nurs Res. 2005;23:179-211. http://www.ncbi.nlm.nih.gov/pubmed/16350766

4. Karam E, Kypri K, Salamoun M . Alcohol use among college students: an international perspective. Curr Opin Psychiatry. 2007;20(3):213-221. http://www.medscape.com/viewarticle/556150

5. Mukamal KJ. Overview of the risks and benefits of alcohol consumption. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2010.

6. Prat G, Adan A, Sánchez-Turet M. Alcohol hangover: a critical review of explanatory factors. Hum Psychopharmacol. 2009;24(4):259-267. http://www.ncbi.nlm.nih.gov/pubmed/19347842

7. Prat G, Adan A, Pérez-Pàmies M, Sànchez-Turet M. Neurocognitive effects of alcohol hangover. Addict Behav. 2008;33(1):15-23. Epub 2007 May 8.

8. Stephens R, Ling J, Heffernan TM, Heather N, Jones K. A review of the literature on the cognitive effects of alcohol hangover. Alcohol Alcohol. 2008;43(2):163-70. Epub 2008 Jan 31.

9. Penning R, van Nuland M, Fliervoet LA, Olivier B, Verster JC. The pathology of alcohol hangover. Curr Drug Abuse Rev. 2010;3(2):68-75.

10. Kim DJ, Kim W, Yoon SJ, et al. Effects of alcohol hangover on cytokine production in healthy subjects. Alcohol. 2003;31(3):167-170.

11. . Kaivola S, Parantainen J, Osterman T, Timonen H. Hangover headache and prostaglandins: prophylactic treatment with tolfenamic acid. Cephalalgia. 1983;3(1):31-36.

12. Rohsenow DJ, Howland J, Arnedt JT, et al. Intoxication with bourbon versus vodka: effects on hangover, sleep, and next-day neurocognitive performance in young adults. Alcohol Clin Exp Res. 2010;34(3):509-518. Epub 2009 Dec 17. http://onlinelibrary.wiley.com/doi/10.1111/j.1530-0277.2009.01116.x/full

13. Pittler MH, Verster JC, Ernst E. Interventions for preventing or treating alcohol hangover: systematic review of randomised controlled trials. BMJ. 2005;331(7531):1515-1518.

14. . Pittler MH, White AR, Stevinson C, Ernst E. Effectiveness of artichoke extract in preventing alcohol-induced hangovers: a randomized controlled trial. CMAJ. 2003;169(12):1269-1273.

15. Wiese J, McPherson S, Odden MC, Shlipak MG. Effect of Opuntia ficus indica on symptoms of the alcohol hangover. Arch Intern Med. 2004;164(12):1334-1340. http://archinte.ama-assn.org/cgi/content/full/164/12/1334

 

The Complicated Story of Saturated Fat

November 8, 2013

By Gregory Katz, MD

Faculty Peer Reviewed

Everyday in clinic, we tell our patients to choose foods low in saturated fat. Because these foods raise plasma cholesterol, the thinking goes, they cause heart disease. Today, every major medical organization – from the American Heart Association to the Harvard School of Public Health to the USDA [1-3] – recommends a diet low in saturated fat to prevent and treat heart disease. The fat-cholesterol-heart disease connection is so thoroughly integrated into both medicine and popular culture that it’s become dogma. But since the initial data on saturated fat and cholesterol were published, our understanding of heart disease and cholesterol has significantly improved. We’ve moved from looking at total cholesterol to measuring LDL, HDL, and triglycerides. And as we better understand the pathophysiology of vascular disease, we may start to move away from cholesterol and directly measure lipoproteins instead.[4] But even as our risk factor assessment has evolved, the diets we recommend to our patients have not. Are we due for a more nuanced approach to evidence-based dietary recommendations? Let’s take a look at the evidence.

The Early Observational Research

The first hypothesis that saturated fat might cause heart disease was developed more than a half century ago from data on the eating patterns of various nations. Back in the 1950s, researchers noted the epidemiologic relationship between heart disease and saturated fat consumption.[5,6,7] These associations were reinforced by data from the Framingham Heart Study which showed an association between hyperlipidemia and heart disease.[8] Critics at the time noted flaws in the original epidemiologic research, pointing out that additional available data would eliminate the saturated fat-heart disease association.[9] And while the Framingham study did find that cardiovascular disease was five times more likely for men with cholesterol over 260 than under 200, there was no difference between these groups in the type or quantity of fat consumed. The investigators also noted that cholesterol has “no predictive value” for women. And data on plasma cholesterol doesn’t necessarily tell us much about the effect on heart disease. A 1969 report from the National Heart, Lung, and Blood Institute stated, “It is not known whether dietary manipulation has any effect whatsoever on coronary heart disease.”[10]

Metabolic Ward Data

Dietary research is notoriously hard to carry out. Researchers often rely on food frequency questionnaires to determine what participants in the study ate. Trusting their data requires placing faith in the ability of patients to recall exactly how frequently they eat various types of food. Many researchers believe these questionnaires to be a totally unreliable method of quantifying what people actually eat.[11] Investigations on institutionalized patients provide a way around this data collection conundrum. The Finnish Mental Hospital Trial and the Los Angeles Veterans Adminstration Study are the two most well known papers in this area. The Finnish trial was a crossover study looking at patients in two psychiatric hospitals in Helsinki; one hospital served its patients full fat milk and butter while the other served unsaturated vegetable oils and filled milk (milk that has been filtered and had its fat replaced by emulsified vegetable oil). At the end of 6 years, the hospitals switched diets. The Finnish study found a 50% relative risk reduction in cardiovascular mortality (although no change in total mortality) in male patients fed the low saturated fat diet.[12] Critics of the Finnish study have noted that the study was poorly controlled: almost half of the participants either entered or left the study over its 12 year duration and sugar consumption varied by more than 50% over the course of the trial. The Los Angeles VA study found an 18% relative risk reduction in cardiovascular deaths by replacing animal fat with vegetable oil, but no difference in overall mortality.[13]

Newer research and confounding observations

More recent investigations have only served to complicate this issue further. After a 2008 expert meeting, the Food and Agricultural Organization of the WHO concluded that “Insufficient evidence relating to effect on the risk of heart disease in replacing saturated fat with carbohydrates” and “Probable evidence that replacing saturated fats with refined carbohydrates may increase risk of heart disease and favor metabolic syndrome development.”[14] The Women’s Health Initiative found that a reduction in saturated fat did not significantly reduce the risk of heart disease or stroke.[15] The A to Z weight loss study published in JAMA found better blood pressure and lipid profiles in patients following the Atkins diet compared to those reducing their saturated fat intake.[16] A 2010 meta-analysis of prospective cohort studies looking at saturated fat and heart disease concluded, “There is no significant evidence for concluding that dietary saturated fat is associated with an increase in CVD.”[17]

While many of the studies investigating the effect of diet on health look at proxies for cardiovascular disease like cholesterol levels and blood pressure instead of measuring hard outcomes like cardiac events and mortality, others confound the effect of dietary changes by measuring the effects of multiple simultaneous interventions. The most famous example of this is Dr. Dean Ornish, who has demonstrated an incredible impact on cardiovascular disease through his research on comprehensive lifestyle changes.[18] Dr. Ornish attributes the effect to his ultra low fat diet, but his is still a hypothesis waiting to be rigorously tested.

Reconciling Discordant Observations: The Vital Importance of Replacement Nutrients

Caveats abound in the research on diet and heart disease and we must take caution before drawing conclusions about healthy eating. When counseling our patients, it is vital to remember that decreasing saturated fat changes two variables in the food consumption equation: the removal of saturated fat and the addition of something else to replace it. Indeed, the replacement that our patients choose is likely to be the factor that determines whether a reduction in saturated fat consumption is helpful or harmful.

A look at some other populations provides useful context. When the Tokelau people, Pacific Islanders who consume more than half of their calories from saturated fat, migrate to New Zealand, their saturated fat consumption goes down by half. But their rates of heart attack go up.[19] The Masai, an African tribe, are another excellent example. When they are young, they eat a diet almost exclusively composed of blood, milk, and meat, at least one third of calories from saturated fat.[20]  As they get older, the Masai that continue this diet are remarkably free of atherosclerosis, even after age 60.[21] But those Masai that reduce their consumption of these substances high in saturated fat and replace them with flour, sugar, and shortening begin to develop atherosclerosis.[22]

Conclusions

Telling patients to reduce saturated fat consumption without giving them instructions on what to replace it with is a gamble. While the evidence suggests that replacing saturated fat with unsaturated fat reduces the risk of cardiovascular disease, it appears that replacing saturated fat with carbohydrates tends to worsen insulin sensitivity and lead to development of metabolic syndrome.[23,24,25].

A 2011 Cochrane Review found that replacing saturated fat with unsaturated fat can reduce relative risk of cardiovascular events by 14%, which equates to a 1% absolute risk reduction over two years.[26] This is a modest, albeit significant benefit for a major lifestyle change. So we should be open with patients about the magnitude of risk reduction from adopting our proposed dietary recommendations. And we should also be careful about how we frame the changes, being honest about the risk they face by substituting carbohydrates for saturated fat.

This absolute risk reduction is one of the most important take home points when thinking about evidence based dietary recommendations. Smoking cessation and blood pressure control are likely to be lifestyle interventions with a greater magnitude of benefit than saturated fat reduction. We should allocate time in our clinical practices to discuss lifestyle modification, but we should also be mindful of the absolute benefits that we hope to attain.

Dr. Gregory Katz is a 2nd year resident at NYU School of Medicine

Peer reviewed by Robert Donnino, MD, Cardiology Section Editor, Clinical Correlations

Image courtesy of Wikimedia Commons

References:

1. http://www.heart.org/HEARTORG/GettingHealthy/FatsAndOils/Fats101/Saturated-Fats_UCM_301110_Article.jsp#.T2lvJmKXQ-A

2. http://www.hsph.harvard.edu/nutritionsource/what-should-you-eat/fats-and-cholesterol/

3. http://www.health.gov/dietaryguidelines/dga2005/document/html/chapter6.htm

4. https://www.clinicalcorrelations.org/?p=5748

5. Keys A. Atherosclerosis: A problem in newer public health. Mount Sinai Hosp NY, 20 (1953), pp. 118–139 http://www.ncbi.nlm.nih.gov/pubmed/13085148

6. Keys A. Coronary heart disease in seven countries. Circulation, 41 (Suppl. 1) (1970), pp. 1–211

7. A. Keys, A. Menotti, M.J. Karvonen et al. The diet and 15-year death rate in The Seven Countries Study. Am J Epidemiol, 124 (1986), pp. 903–915

8. Kannel WB, Gordon T. The Framingham diet study: Diet and the regulation of serum cholesterol. The Framingham study. An epidemiologic investigation of cardiovascular disease. Section 24, Washington, DC, 1970.

9. J. Yerushalmy, H.E. Hilleboe. Fat in the diet and mortality from heart disease. A methodologic note. NY State J Med, 57 (1957), pp. 2343–2354

10. Taubes G. The Soft Science of Dietary Fat. Science 30 March 2001. Vol 291.

11. Schaefer E et al. Lack of efficacy of a food frequency questionairre in assessing dietary macronutrient intakes in subjects consuming diets of known composition. Am J Clinical Nutrition. March 2000;71(3):746-751  http://ajcn.nutrition.org/content/71/3/746.long

12. Miettinen M et al. Effect of cholesterol lowering diet on mortality from coronary disease and other causes. A twelve year trial in men and women. Lancet. 1972 Oct 21;2(7782):835-8.

13. Dayton S et al. A controlled diet high in unsaturated fat in preventive complications of atherosclerosis. Circulation 1969;40(11):1-63

14. http://www.fao.org/docrep/013/i1953e/i1953e00.pdf

15. Howard BV, Van Horn L, et al. Low fat dietary pattern and risk of cardiovascular disease: Women’s Health Initiative randomized controlled dietary modification trial. JAMA 2006 Feb 8; 295(6):655-66

16. Gardener C, King A et al. Comparison of the Atkins, Zone, Ornish, and LEARN Diets for Change in Weight and Related Risk Factors Among Overweight Premenopausal WomenThe A TO Z Weight Loss Study: A Randomized Trial. JAMA. 2007;297(9):969-977. doi:10.1001/jama.297.9.969.

17. Siri-Tarino PW, Sun Q, Hu FB, Krauss RM. Saturated fat, carbohydrate, and cardiovascular disease. Am J Clin Nutr. 2010 Mar;91(3):502-9. Epub 2010 Jan 20.

18. Ornish D, Scherwitz LW, Billings JH, Brown SE, Gould KL, Merritt TA, Sparler S, Armstrong WT, Ports TA, Kirkeeide RL, Hogeboom C, Brand RJ. Intensive lifestyle changes for reversal of coronary heart disease. JAMA. 1998 Dec 16;280(23):2001-7.  http://www.ncbi.nlm.nih.gov/pubmed/9863851

19. Stanhope JM, Sampson VM. The Tokelau Migrant Study. J. Chronic Disease. 1981;34(2-3):45-55.

20. Ho KJ et al. The Masai of East African: some unique biological characteristics. Arch Pathol. 1971 May;91(5):387-410

21. Biss K et al. The Masai’s protection against atherosclerosis. Pathologic Microbiology. 1970;35(1):198-204.

22. Mann GV. Atherosclerosis in the Masai. Am J Epidemiology. 1972 Jan;95(1):26-37  http://aje.oxfordjournals.org/content/95/1/26.short

23. Volek et al. Carbohydrate restriction has a more favorable impact on the metabolic syndrome than low fat diet. Lipids 2009;44(4):297-309

24. Siri PW, Krauss RM. Influence of dietary carbohydrate and fat on LDL and HDL particle distribution. Curr Atherosclerosis Rep 2005 Nov;7(6):455-9  http://www.ncbi.nlm.nih.gov/pubmed/16256003

25. Weinberg SL. The diet-heart hypothesis: a critique. J Am Coll Cardiology. 2004:43(5):731-733

26. Hooper L et al. Reduced or modified dietary fat for preventing cardiovascular disease. Cochrane Database System Review. 2011 July 6;(7):CD002137  http://www.ncbi.nlm.nih.gov/pubmed/11687015

The Health Risks and Benefits of Drinking Coffee

July 17, 2013

By Anish Parikh, MD

Faculty Peer Reviewed

At some point during my medical training, drinking coffee went from being an enjoyable, even indulgent, activity to being my primary weapon against fatigue and its associated decline in cognitive function. Although realizing this made me critically, and somewhat resentfully, evaluate my own consumption of coffee, it also made me think more generally about the role of coffee in today’s world. In the hospital, where many of us spend most of our time, coffee is ubiquitous. However, such avid consumption of coffee is not unique to the healthcare setting. Worldwide, coffee is the most common beverage after water, with approximately 500 billion cups consumed annually, and this number continues to increase [1]. With such widespread consumption, it becomes important to think about the effects coffee may have on our health.

The neuropsychiatric effects of coffee are perhaps the most well known. The caffeine within coffee stimulates excitatory neurotransmitters by antagonizing adenosine receptors throughout the nervous system [2]. This leads to improved reasoning, attention, memory, energy, and concentration [3]. Caffeine also has the interesting ability to both generate and alleviate headaches. A meta-analysis of randomized controlled trials studying the use of coffee to treat migraine and tension headaches found analgesic effects with caffeine doses of at least 65 mg, or approximately 1 cup of coffee [4]. In contrast, another study showed that daily coffee drinkers were more likely to have chronic migraines and analgesic rebound headaches compared to those who do not regularly drink coffee [5]. Caffeine intake has even been associated with the development of acute psychiatric symptoms such as anxiety, insomnia, irritability, and panic attacks [6].

There are other neuropsychiatric effects of coffee that are important to consider. Although the DSM-IV does not officially recognize caffeine dependence and abuse, several studies have suggested that high caffeine intake can lead to dependence and abuse in ways similar to other psychoactive substances [7]. Studies have also demonstrated an increase in other addictive behaviors in heavy coffee drinkers. Lopez-Garcia and colleagues found alcohol use to be 50-100% higher among women who drank over 6 cups of coffee each day when compared to those who drink 1 cup or less [8]. Another important consequence of prolonged heavy coffee consumption is withdrawal, which can cause headache, fatigue, decreased energy and concentration, depression, and irritability. These symptoms can occur after abstaining from daily doses of caffeine as low as 100 mg per day, although symptom incidence and severity increases with higher doses [9]. Withdrawal begins within 12-24 hours after the last cup, peaks at 1-2 days, and usually resolves by 8-9 days [9]. Interestingly, re-administration of caffeine can reverse symptoms within 30-60 minutes, a fact that many of us have probably already empirically figured out [9].

Coffee has also been shown to have important implications for more complicated neurological problems. One important meta-analysis conducted in 2002 found evidence of a dose-response relationship between coffee intake and decreased risk of Parkinson disease [10]. Although the mechanism for this relationship remains unclear, it seems that the rich supply of anti-oxidants in coffee promotes the expression of enzymes that mitigate the neurodegenerative effects of free radicals [11]. Coffee has also been found to activate certain pathways, such as the Nrf2-ARE pathway, that strengthen endogenous neuroprotective mechanisms to help control the development of Parkinson’s [11]. Studies have also shown that moderate daily caffeine intake may decrease the risk of Alzheimer’s disease [12]. This is thought to occur because caffeine may reduce the expression of genes such as presenilin-1, which is important in the formation of the amyloid plaques that characterize this disease [12].

The effects of coffee on the development of malignancy remain controversial. Both positive and negative associations between coffee consumption and cancer risk have been described for most types of cancer [11]. However, results that support these various associations remain contentious, as studies reporting conflicting results continue to emerge. This inconsistency is thought to be due at least in part to the complicated interactions between environmental and genetic factors in the development of malignancy, as well as to imperfect study design. At this point, it seems that coffee consumption may indeed be associated with decreased risk of hepatocellular, colorectal, prostate, and renal cancers [11,23]. In addition, a recent meta-analysis suggests that coffee is weakly associated with breast cancer risk in postmenopausal women [22]. However, much further investigation is needed before clear conclusions can be drawn.

A great deal of research has also been done to examine how coffee affects cardiovascular health. Caffeine has been shown to increase inotropy by inhibiting the negative inotropic effects of adenosine and by increasing both intracellular calcium and myocardial sensitivity to calcium [13-15]. Other studies looking at the arrhythmogenic potential of coffee have found that this only occurs at doses much higher than those typically consumed, although patients with underlying cardiac disease appear to be at increased risk [16,17]. Still other studies have found that by increasing sympathetic activity coffee can acutely increase blood pressure by up to 10 mmHg, but only in non-habitual coffee drinkers [18]. Despite these findings, several studies found that drinking up to 6 cups of coffee daily was not associated with an increased risk of chronic hypertension [19]. Another study using the same data found that coffee did not affect plasma lipid levels and cardiovascular disease risk, even with consuming more than 6 cups of coffee each day [8]. Follow-up studies have shown that coffee was not associated with increased all-cause or cardiovascular mortality, and that in women it may actually be cardioprotective [20,21].

As evidenced by the studies described above, examining the health effects of coffee has become an exciting area of research. Although most of this work focuses on associations with neuropsychiatric, cardiovascular, and malignant disease, newer studies are branching out even further to study, for instance, the effects of coffee on the risk of developing type 2 diabetes or osteoporosis, or its effects on the gut microbiome. While at this point it seems that there may be a slight overall benefit from drinking coffee, it is important to realize that most of the existing literature recommends consumption in moderation, or no more than 2-3 cups per day. Regardless, further research needs to be done in order to more clearly understand the exact health risks and benefits of drinking coffee.

Dr. Anish Parikh is a 1st year resident at NYU Langone Medical Center

Peer reviewed by Brian Greet, MD, Associate Editor, Clinical Correlations

Image courtesy of Wikimedia Commons

References:

1. Clarke RJ, Vitzthum OG, eds. Coffee: Recent Developments. Berlin: Blackwell Science; 2001.  http://onlinelibrary.wiley.com/doi/10.1002/9780470690499.fmatter/pdf

2. Fredholm BB, Bättig K, Holmén J, Nehlig A, Zvartau EE. Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev. 1999;51(1):83-133.  http://www.ncbi.nlm.nih.gov/pubmed/10049999

3. Ker K, Edwards PJ, Felix LM, Blackhall K, Roberts I. Caffeine for the prevention of injuries and errors in shift workers. Cochrane Database Syst Rev. 2010;(5):CD008508.  http://www.ncbi.nlm.nih.gov/pubmed/20464765

4. Goldstein J, Silberstein SD, Saper JR, Ryan RE Jr, Lipton RB. Acetaminophen, aspirin, and caffeine in combination versus ibuprofen for acute migraine: results from a multicenter, double-blind, randomized, parallel-group, single-dose, placebo-controlled study. Headache. 2006;46(3):444-453.

5. Bigal ME, Sheftell FD, Rapoport AM, Tepper SJ, Lipton RB. Chronic daily headache: identification of factors associated with induction and transformation. Headache. 2002;42(7):575-581.  http://www.ncbi.nlm.nih.gov/pubmed/12482208

6. Griffiths RR, Juliano LM, Chausmer AL. Caffeine pharmacology and clinical effects. In: Graham AW, Schultz TK, Mayo-Smith M, et al, eds. Principles of Addiction Medicine, 3rd ed. Chevy Chase, MD: American Society of Addiction Medicine; 2003:193-224.

7. Ogawa N, Ueki H. Clinical importance of caffeine dependence and abuse. Psychiatry Clin Neurosci. 2007;61(3):263-268.  http://www.ncbi.nlm.nih.gov/pubmed/17472594

8. Lopez-Garcia E, van Dam RM, Willett WC, et al. Coffee consumption and coronary heart disease in men and women: a prospective cohort study. Circulation. 2006;113(17):2045-2053.

9. Juliano LM, Griffiths RR. A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features. Psychopharmacology (Berl). 2004;176(1):1-29.  http://www.ncbi.nlm.nih.gov/pubmed/15448977

10. Hernán MA, Takkouche B, Caamaño-Isorna F, Gestal-Otero JJ. A meta-analysis of coffee drinking, cigarette smoking, and the risk of Parkinson’s disease. Ann Neurol. 2002;52(3):276-284.  http://www.ncbi.nlm.nih.gov/pubmed/12205639

11. Butt MS, Sultan MT. Coffee and its consumption: benefits and risks. Crit Rev Food Sci Nutr. 2011;51(4):363-373.

12. Arendash GW, Schleif W, Rezai-Zadeh K, et al. Caffeine protects Alzheimer’s mice against cognitive impairment and reduced brain beta-amyloid production. Neuroscience. 2006;142(4):941-952.

13. Scholz H. Inotropic drugs and their mechanisms of action. J Am Coll Cardiol. 1984;4(2):389-397.  http://www.sciencedirect.com/science/article/pii/S0735109784802314

14. Konishi M, Kurihara S. Effects of caffeine on intracellular calcium concentrations in frog skeletal muscle fibres. J Physiol. 1987;383:269-283.

15. Hess P, Wier WG. Excitation-contraction coupling in cardiac Purkinje fibers: effects of caffeine on the intracellular [Ca2+] transient, membrane currents, and contraction. J Gen Physiol. 1984;83(3):417-433.

16. Myers MG. Caffeine and cardiac arrhythmias. Ann Intern Med. 1991;114(2):147-150.

17. Cannon ME, Cooke CT, McCarthy JS. Caffeine-induced cardiac arrhythmia: an unrecognised danger of healthfood products. Med J Aust. 2001;174(10):520-521.

18. Corti R, Binggeli C, Sudano I, et al. Coffee acutely increases sympathetic nerve activity and blood pressure independently of caffeine content: role of habitual versus nonhabitual drinking. Circulation. 2002;106(23):2935-2940.  http://circ.ahajournals.org/content/106/23/2935.full

19. Winkelmayer WC, Stampfer MJ, Willett WC, Curhan GC. Habitual caffeine intake and the risk of hypertension in women. JAMA. 2005;294(18):2330-2335.

20. Lopez-Garcia E, van Dam RM, Li TY, Rodriguez-Artalejo F, Hu FB. The relationship of coffee consumption with mortality. Ann Intern Med. 2008;148(12):904-914.  http://www.ncbi.nlm.nih.gov/pubmed/18559841

21. Bertoia ML, Triche EW, Michaud DS, et al. Long-term alcohol and caffeine intake and risk of sudden cardiac death in women. Am J Clin Nutr. 2013;97(6):1356-1363.

22. Jiang W, Wu Y, Jiang X. Coffee and caffeine intake and breast cancer risk: An updated dose-response meta-analysis of 37 published studies. Gynecol Oncol. 2013;129(3):620-629.

23. Discacciati A, Orsini N, Andersson SO, et al. Coffee consumption and risk of localized, advanced, and fatal prostate cancer: a population-based prospective study. Ann Oncol. 2013 Mar 18;[Epub ahead of print].

Is There Evidence to Support a Vegetarian Diet in Common Chronic Diseases?

June 20, 2013

By Christopher Graffeo

Faculty Peer Reviewed

In the age of prevention, primary care is more empowered than ever to educate patients on reducing their risk for common chronic diseases by promoting behavior modifications early in the natural history. In the clinic, this means a focus on hyperlipidemia, hypertension, and diabetes—risk factors that play synergistic roles in causing a wide array of diseases with tremendous morbidity and mortality. Given the large number of risk factors that co-exist for so many patients, astute clinicians are aiming for the lifestyle changes likely to yield the most bang for their preventive buck—that is, the interventions that have a significant impact on the most disease processes. Although nutrition counseling has received significant attention as a high-yield primary care priority, one especially strong recommendation with many benefits for all of the common chronic disease is regularly overlooked: the vegetarian diet.

One of the clearest ways in which a vegetarian diet improves patient health is by reducing rates of obesity and overweight. The hazards of obesity are well established in both men and women, and include increased risk of coronary artery disease, diabetes, hypertension, stroke, and osteoarthritis [1]. Obesity is further associated with decreased life expectancy by at least 1 year, and increased individual health care costs in excess of $10,000 [1,2]. Numerous studies have noted a significant association between vegetable-based diets and lower weight, including a 2009 population study of over 60,000 patients published by the American Diabetes Association that demonstrated a 5-unit body-mass index (BMI) difference between patients eating no animal products and omnivorous controls [3]. Mechanistically, studies have shown that the weight loss experienced in adopting a vegetarian diet involves a number of interrelated metabolic processes. Increased dietary fiber and complex carbohydrate intake coupled with decreased dietary protein collectively translate to delayed gastric emptying, increased transit time, earlier satiety, lower total caloric intake, and increased post-prandial energy expenditures during digestion [4]. Perhaps most importantly, the physiological mechanisms of weight loss synergize with other interventions in the treatment of other related diseases, yielding profound improvements in hyperlipidemia, hypertension, and diabetes [2].

Data supporting the positive effects of a vegetarian diet on hyperlipidemia and heart disease are compelling, especially as heart disease remains the leading cause of death for both men and women in America in 2012 [5]. A meta-analysis of 5 prospective studies involving more than 76,000 patients showed 31% less death from ischemic heart disease among male vegetarians as compared with nonvegetarians, and 21% less in female vegetarians [6]. Although many factors play a role in this transformation, a large fraction of the impact is attributable to a 14% decrease in total serum cholesterol observed between lacto-ovo-vegetarians and non-vegetarians, described in a meta-analysis of 9 prospective studies—a finding that is reproduced in comparisons between overweight vegetarians and nonvegetarians with a normal BMI [2,7,8]. The cholesterol-lowering effect is derived from several components of the vegetarian diet including decreased cholesterol and saturated fat intake along with increased dietary plant fiber and soy [9,10,11]. Of note, although smaller doses of soy have not been similarly studied, a 25 g daily portion of soy included in either a vegetarian or an omnivorous diet has been shown to increase plasma HDL, reduce total cholesterol, and provide a source of isoflavones—a subset of phytoestrogens that promote endothelial function and compliance, mitigating atherosclerotic damage [12,13,14].

Blood pressure is also improved dramatically by a vegetarian diet. Not only have many observational studies have shown that vegetarians consistently exhibit lower blood pressures than matched omnivorous controls, but randomized clinical trials have further demonstrated a significant decrease in blood pressure following the institution of a vegetarian diet in both hypertensive and normotensive patients [4,15,16,17]. Evidence supports a multifactorial mechanism centered on diet-associated weight loss, with one study showing an overall decrease in the incidence of hypertension from 40.5% to 18.9% among patients who maintained a weight loss of 2.4 kg throughout 7 years of follow-up [18,19]. Weight loss, however, is only part of the picture, with other studies demonstrating that the association between a vegetarian diet and improved blood pressure remains significant after statistical adjustment for changes due to weight loss and baseline differences in BMI between populations. Data from observational studies and meta-analyses generally agree that increasing dietary fiber, potassium, and magnesium all contribute to improved hypertension control [20,21,22,23]. An area of interesting new research focuses on the role of antioxidants, which are abundant in fruits and vegetables. Antioxidant-rich diets yield higher levels of vitamins C and E, and ?- and ?-carotene, which correlate with decreases in systolic and diastolic blood pressure among both hypertensive and normotensive patients following 6 months of dietary supplementation [24,25,26]. The leading theory connecting antioxidants to blood pressure control focuses on regulation of nitric oxide synthase, whose inhibition is thought to underlie the impaired endothelial vasodilation that characterizes essential hypertension [27]. Increased dietary antioxidants limit this effect by removing excess superoxide anion—an in vivo inactivator of nitric oxide [28].

Perhaps the most important frontier for counseling patients on the benefits of a vegetarian diet is diabetes. Diabetes mellitus is a crippling disease that currently affects at least 8.3% of the American population, which amounts to 25.8 million patients—as well as another 79 million patients with prediabetes [29]. Observational studies have consistently demonstrated that patients with either normal glycemic control or prediabetes who adhere to vegetarian diets are half as likely to develop diabetes mellitus as those eating omnivorously, while clinical trials in diabetes have shown significant improvements in glycemic control on both vegetarian and vegan diets as compared to conventionally prescribed diabetic diets or no nutritional intervention [30]. As in hypertension, weight loss accounts for a substantial fraction of the observed clinical improvement in diabetic vegetarians, but other independent factors have also been shown to make significant contributions to the overall effect on improved glycemic control.

Reducing dietary fats has been shown in case-control studies to reduce intramyocellular lipid content by up to 31% in diets devoid of animal products when compared to weight-matched omnivorous controls, an essential finding given that intramyocellular lipid content is strongly associated with insulin resistance [31,32,33]. In parallel, the increase in dietary complex carbohydrates that typically accompanies a decrease in dietary animal products in a vegetarian diet further improves insulin sensitivity, acting synergistically to mitigate hyperglycemia [14].

Departing from the physiological principle that less bioavailable non-heme iron sources predominate in the vegetarian diet, observational studies have shown that increased serum ferritin correlates with insulin resistance and is predictive of type 2 diabetes—a finding that has been confirmed by a case-control study comparing lacto-ovo-vegetarians against age- and BMI-matched omnivorous controls [34,35,36]. These results are further supported by a small trial that used phlebotomy to reduce the serum iron levels of 6 omnivorous diabetics to the average range for vegetarian patients, an intervention that yielded a 40% improvement in insulin sensitivity [37].

Dietary fiber—especially viscous fiber—has been shown by observational studies to be associated with decreased incidence of diabetes, as well as improved insulin sensitivity among diabetics [38]. Fiber also plays a role in glycemic control by delaying gastric emptying, increasing satiety, and increasing the thickness of the unstirred water layer, thereby slowing the rate of glucose absorption, effects that collectively promote significant weight loss and insulin sensitivity [39]. Later in the digestive process, fiber undergoes colonic fermentation to propionate—an inhibitor of hepatocyte gluconeogenesis [40]. Establishing what this means in clinical terms, a randomized cross-over study of type 2 diabetics on a diet containing 50 g of daily fiber for 6 weeks showed improvements of 10% and 12% in 24-hour glucose and insulin concentrations as compared to diabetic controls consuming only 24 g of daily fiber [41]. Further, although few studies have monitored hemoglobin A1c as their primary endpoint, a 2009 randomized controlled trial that put 99 diabetic patients on 22 weeks of either a vegan diet, the American Diabetes Association’s recommended low-fat low-glycemic-index diet, or nutritional counseling only (provided to patients in all 3 treatment arms) showed decreases in hemoglobin A1c of 0.96%, 0.56%, and 0.36%, respectively—strong evidence supporting the vegetarian diet as a powerfully effective intervention for long-term improvement of glycemic control in diabetic patients [42].

Counseling your patients to adopt a vegetarian diet can bear extraordinary fruits in many areas of their health, although those effects also depend on portion control, limited snacking, and reduction or elimination of sugar-sweetened beverages, as well as regular exercise and good sleep hygiene [43]. Older arguments against a vegetarian diet including cost and nutritional incompleteness have consistently been refuted, with strong, reproducible evidence demonstrating that vegetarian meals are not only cheaper to prepare at home, but also that prior evidence of nutritional deficits could likely be ascribed to poor health literacy and meal planning—obstacles that can be overcome through patient counseling and nutrition education and support [44,45]. In reality, the only nutritional deficiency among vegetarians supported by clinical evidence is vitamin B12, which is available both in the limited animal products available to lacto-ovo-vegetarians and in the many fortified soy and grain products developed for vegetarians and vegans. Although there has been considerable controversy over access to healthy foods for low-income patients, two studies published this year in the American Journal of Preventive Medicine and Social Sciences & Medicine show flaws in the “food desert” model, with evidence demonstrating broad access to supermarkets and grocery stores throughout almost all of the urban areas previously thought to be lacking sources of healthy foods [45,46]. With this in mind, one could say that the only true obstacles to promoting a healthy, vegetarian diet are misinformation and negative cultural attitudes regarding vegetarianism. Overcoming these barriers is achievable, and the goal of healthy, nutritious eating through a plant-based diet is within reach. Advocacy, counseling, and prevention have rarely been so important, and the potential benefits—especially for patients with obesity, hyperlipidemia, hypertension, or diabetes—are almost impossible to overstate.

Commentary by Dr. Sapana Shah

Dramatic results can be seen when patients implement a plant-based vegetarian diet that focuses on fruits, vegetables, whole grains, and legumes. I have found the Physician’s Committee for Responsible Medicine website (http://www.pcrm.org) to be immensely helpful in educating myself on how to counsel patients on making such dietary changes. In addition to free nutritional continuing medical education courses for providers, their website contains a health and nutrition section that includes downloadable pamphlets for patients on how to start a vegetarian diet, available in both English and Spanish. The literature is patient-centered and answers many of the questions they may have when they get started (such as will they get enough protein, calcium, iron, and nutrients on a plant-based diet) and includes simple recipes.

Christopher Graffeo is a third year medical student at NYU School of Medicine

Peer reviewed by Sapana Shah, MD, Department of Medicine, NYU Langone Medical Center

Image courtesy of Wikimedia Commons

References

1. Thompson D, Edelsberg J, Colditz GA, Bird AP, Oster G. Lifetime health and economic consequences of obesity. Arch Intern Med. 1999;159(18):2177-2183.  http://www.ncbi.nlm.nih.gov/pubmed/10527295

2. Thorogood M, McPherson K, Mann J. Relationship of body mass index, weight, and height to plasma lipid levels in people with different diets in Britain. Community Med. 1989;11(3):230-233.

3. Tonstad S, Butler T, Yan R, Fraser R. Type of vegetarian diet, body weight, and prevalence of type 2 diabetes. Diabetes Care. 2009;32(5):791-796.

4. Berkow SE, Barnard ND. Blood pressure regulation and vegetarian diets. Nutr Rev. 2005;63(1):1-8.  http://www.ncbi.nlm.nih.gov/pubmed/15730229

5. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics—2012 update: a report from the American Heart Association. Circulation. 2012;125(1):e2-e220.

6. Key TJ, Fraser GE, Thorogood M, et al. Mortality in vegetarians and nonvegetarians: detailed findings from a collaborative analysis of 5 prospective studies. Am J Clin Nutr. 1999;70(3 Suppl):516S-524S.

7. Resnicow K, Barone J, Engle A, et al. Diet and serum lipids in vegan vegetarians: a model for risk reduction. J Am Diet Assoc. 1991;91(6):447-453.

8. Sacks FM, Castelli WP, Donner A, Kass EH. Plasma lipids and lipoproteins in vegetarians and controls. N Engl J Med. 1975;292(22):1148-1151.

9. Brown L, Rosner B, Willett WW, Sacks FM. Cholesterol-lowering effects of dietary fiber: a meta-analysis. Am J Clin Nutr. 1999;69(1):30-42.

10. Smit E, Nieto FJ, Crespo CJ. Blood cholesterol and apolipoprotein B levels in relation to intakes of animal and plant proteins in US adults. Br J Nutr. 1999;82(3):193-201.  http://www.ncbi.nlm.nih.gov/pubmed/10655966

11. Anderson JW, Johnstone BM, Cook-Newell ME. Meta-analysis of the effects of soy protein intake on serum lipids. N Engl J Med. 1995;333(5):276-282.

12. Anderson JW, Bush HM. Soy protein effects on serum lipoproteins: a quality assessment and meta-analysis of randomized, controlled studies. J Am Coll Nutr. 2011;30(2):79-91.

13. Simons PC, Algra A, Bots ML, Grobbee DE, van der Graaf Y. Common carotid intima-media thickness and arterial stiffness: indicators of cardiovascular risk in high-risk patients. The SMART Study (Secondary Manifestations of ARTerial disease). Circulation. 1999(9);100:951-957.

14. Wiseman H, O’Reilly JD, Adlercreutz H, et al. Isoflavone phytoestrogens consumed in soy decrease F(2)-isoprostane concentrations and increase resistance of low-density lipoprotein to oxidation in humans. Am J Clin Nutr. 2000;72:395-400.

15. Rouse IL, Beilin LJ, Armstrong BK, Vandongen R. Blood-pressure-lowering effect of a vegetarian diet: controlled trial in normotensive subjects. Lancet. 1983;1(8314-5):5-10.

16. Margetts BM, Beilin LJ, Vandongen R, Armstrong BK. Vegetarian diet in mild hypertension: a randomised controlled trial. Br Med J (Clin Res Ed). 1986; 293(6560):1468-1471.

17. Margetts BM, Beilin LJ, Armstrong BK, Vandongen R. A randomized control trial of a vegetarian diet in the treatment of mild hypertension. Clin Exp Pharmacol Physiol. 1985;12(3):263-266.

18. The Trials of Hypertension Prevention Collaborative Research Group. Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high-normal blood pressure. Arch Int Med. 1997;157(6):657-667.

19. He J, Whelton PK, Appel LJ, Charleston J, Klag MJ. Long-term effects of weight loss and dietary sodium reduction on incidence of hypertension. Hypertension. 2000;35(2):544-549.

20. He J, Whelton PK. Effect of dietary ?ber and protein intake on blood pressure: a review of epidemiological evidence. Clin Exp Hypertens. 1999;21(5-6):785-796.

21. Whelton PK, He J, Cutler JA, et al. Effects of oral potassium on blood pressure: meta-analysis of randomized controlled clinical trials. JAMA. 1997;277(20):1624-1632.  http://www.ncbi.nlm.nih.gov/pubmed/9168293

22. Cappuccio FP, MacGregor GA. Does potassium supplementation lower blood pressure? A meta-analysis of published trials. J Hypertens. 1991;9(5):465-473.

23. Joffres MR, Reed DM, Yano K. Relationship of magnesium intake and other dietary factors to blood pressure: the Honolulu heart study. Am J Clin Nutr. 1987;45(2):469-475.

24. Galley HF, Thornton J, Howdle PD, Walker BE, Webster NR. Combination oral antioxidant supplementation reduces blood pressure. Clin Sci (Lond). 1997; 92:361-365.

25. Haddad EH, Berk LS, Kettering JD, Hubbard RW, Peters WR. Dietary intake and biochemical, hematologic, and immune status of vegans compared with nonvegetarians. Am J Clin Nutr. 1999;70(3 Suppl):586S-593S.

26. John JH, Ziebland S, Yudkin P, Roe LS, Neil HA; Oxford Fruit and Vegetable Study Group. Effects of fruit and vegetable consumption on plasma antioxidant concentrations and blood pressure: a randomised controlled trial. Lancet. 2002;359(9322):1969-1974.

27. Panza JA, García CE, Kilcoyne CM, Quyyumi AA, Cannon RO 3rd. Impaired endothelium-dependent vasodilation in patients with essential hypertension: evidence that nitric oxide abnormality is not localized to a single signal transduction pathway. Circulation. 1995;91(6):1732-1738.

28. Rivas M, Garay RP, Escanero JF, Cia P Jr, Cia P, Alda JO. Soy milk lowers blood pressure in men and women with mild to moderate essential hypertension. J Nutr. 2002;132(7):1900-1902.

29. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). National Diabetes Statistics 2011. Bethesda, Maryland: National Diabetes Information Clearinghouse. Publication No. 11-3892. http://diabetes.niddk.nih.gov/dm/pubs/statistics/NIH.  Published February 2011. Updated December 6, 2011. Accessed June 20, 2012.

30. Fraser G. Vegetarian diets: what do we know of their effect on common chronic disease? Am J Clin Nutr. 2009;89(5):1607S-1612S.

31. Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med. 2004;350(7):664–671.

32. Goff LM, Bell JD, So PW, Dornhorst A, Frost GS. Veganism and its relationship with insulin resistance and intramyocellular lipid. Eur J Clin Nutr. 2005;59(2):291–298.

33. Greco AV, Mingrone G, Giancaterini A, et al. Insulin resistance in morbid obesity: reversal with intramyocellular fat depletion. Diabetes. 2002;51(1):144–151.

34. Jehn M, Clark JM, Guallar E. Serum ferritin and risk of the metabolic syndrome in U.S. adults. Diabetes Care. 2004;27(10):2422–2428.

35. Fumeron F, Pean F, Driss F, et al. Ferritin and transferrin are both predictive of the onset of hyperglycemia in men and women over 3 years: the data from an epidemiological study on the insulin resistance syndrome (DESIR) study. Diabetes Care. 2006;29(9):2090–2094.

36. Jiang R, Manson JE, Meigs JB, Ma J, Rifai N, Hu FB. Body iron stores in relation to risk of type 2 diabetes in apparently healthy women. JAMA. 2004;291(6):711–717.

37. Hua NW, Stoohs RA, Facchini FS. Low iron status and enhanced insulin sensitivity in lacto-ovo vegetarians. Br J Nutr. 2001;86(4):515–519.

38. Jenkins DJ, Wolever TM, Leeds AR, et al. Dietary fibres, fibre analogues, and glucose tolerance: importance of viscosity. Br Med J. 1978;1(6124):1392–1394.

39. Weickert MO, Pfeiffer AF. Metabolic effects of dietary fiber consumption and prevention of diabetes. J Nutr. 2008;138(3):439–442.

40. Blackburn NA, Redfern JS, Jarjis H, et al. The mechanism of action of guar gum in improving glucose tolerance in man. Clin Sci (Lond). 1984;66(3):329–336.

41. Chandalia M, Garg A, Lutjohann D, von Bergmann K, Grundy SM, Brinkley LJ. Beneficial effects of high dietary fiber intake in patients with type 2 diabetes mellitus. N Engl J Med. 2000;342(19):1392–1398.

42. Barnard ND, Katcher HI, Jenkins DJ, Cohen J, Turner-McGrievy G. Vegetarian and vegan diets in type 2 diabetes management. Nutr Rev. 2009;67(5):255-263.

43. U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans 2010. 7th Edition, Washington, DC: U.S. Government Printing Office. www.dietaryguidelines.gov. Published December 2010. Accessed June 20, 2012.

44. Schwartz-Cassell T. The vegetarian option: cost effective and healthy. Comtemp Longterm Care. 2004;(30):32-33,36.

45. An R, Sturm R. School and residential neighborhood food environment and diet among California youth. Am J Prev Med. 2012;42(2):129-135.

46. Lee H. The role of local food availability in explaining obesity risk among young school-aged children. Soc Sci & Media. 2012;74(8):1193-1203.

Should I Add Sugar or Splenda to My Coffee?

June 6, 2013

By Reda Issa

Faculty Peer Reviewed

As a medical student, I adjusted to waking up at 6 AM every day – with the help of coffee, of course. Living in New York City and its fast-paced routine requires that extra kick those beans provide. So, should I add sugar or Splenda to my coffee? Half a century ago this question did not exist, but obesity was not a word in the Merriam-Webster then. Today, we have to think more carefully.

Non-sucrose based sweeteners can be either natural or artificial. The best known natural sweetener is Stevia, an extract of leaves from Stevia rebaudiana Bertoni that has been used for many years in the traditional treatment of diabetes in South America [1]. Artificial sweeteners have existed since 1879 when saccharin was incidentally discovered by Constantine Fahlberg, who licked his finger after accidentally splashing himself with a substance during an experiment at Johns Hopkins – and found that it was sweet [2]. Currently, the U.S. Food and Drug Administration has five approved artificial sweeteners, including the famous three: saccharin (Sweet’N Low), aspartame (Equal), and sucralose (Splenda). Most of these sweeteners are non-caloric (i.e. it takes 0 kcal/g to metabolize them) [2].

High-sugar foods and beverages are a major cause of weight gain. Substituting sugar with artificial sweeteners that provide very few or no calories seems, logically, to be helpful in the prevention of weight gain. Indeed, a trial in 2002 provided overweight subjects with food containing either sucrose or artificial sweeteners as supplements to their diets. The artificial sweetener–supplemented group took in 105kcal less of daily energy, an amount that prevented the 1.3 kg weight gained by the sucrose group over a 10 week period [3]. The reason for this difference is that subjects consuming the sucrose-containing supplements did not decrease their carbohydrate intakes to compensate for the added calories provided by the supplements, resulting in significant increases in carbohydrate consumption, while the artificial sweetener-supplemented group did not modify their carbohydrate consumption, nor did they need to. Additionally, there was no difference between the two groups in hunger, fullness, and well-being [4]. These results, in addition to those of other similar trials, support the idea that artificial sweeteners significantly reduce body weight [5].

Both the American Heart Association (AHA) and the American Diabetes Association (ADA) recommend limiting added sugars as an important strategy for supporting optimal nutrition and healthy weight, and they state that although evidence is limited, nonnutritive sweeteners may be used in a structured diet to replace sources of added sugars, and that this substitution may result in modest energy intake reductions and weight loss [6]. Physiologically, sucralose does not stimulate insulin, glucagon-like peptide 1 (GLP-1), or glucose-dependent insulinotropic polypeptide (GIP) release, nor does it slow gastric emptying in healthy humans [7]. These artificial sweeteners therefore do not interfere with glucose metabolism and are passed through the gastrointestinal tract with no effect; thus artificial sweeteners may have no therapeutic benefit in the dietary management of diabetes other than as a substitute for carbohydrate.

Aside from weight loss, artificial sweeteners have many other beneficial effects. For example, the use of sucrose substitutes in sweets is believed to have contributed in part to the decline in the prevalence of dental caries in industrialized countries [8]. Stevia specifically was shown to be effective in lowering blood pressure in hypertensive patients, and small studies also report positive results with respect to improved glucose tolerance [1] in addition to some anti-fungal and anti-bacterial properties [9].

All these positive aspects seem to favor the use of non-sugar based sweeteners, so why have they not completely replaced sugar? Some rumors disseminated by the press reported serious adverse effects associated with the use of these substances, many of which have no scientific background Even some of the scientific publications in reliable medical journals, which caught media attention, were not well researched and ignored common statistical knowledge. For example a large study in 1996 titled ‘Increasing brain tumor rates: Is there a link to aspartame?’ linked the increase of brain tumors to the introduction of aspartame, two events that incidentally occurred around the same period. In epidemiology, this correlation is called ‘ecological fallacy’ and is not admissible, since there was no information available regarding whether the individuals who developed brain tumors consumed aspartame [10] The scare was mainly regarding bladder cancer, and it was based on rat studies that showed increased risk; in fact, this study resulted in a ban on saccharin in Canada and a black label in the USA in 1981. However, the National Institute for Environmental Health Sciences removed saccharin as a potential cancer-causing agent in 2000 because it was shown that the cancer-inducing mechanisms in rats do not apply to humans [10]. Many more human studies found no evidence that artificial sweeteners bear a carcinogenic risk, unless very high doses are consumed (greater than 4000 mg/kg body weight per day which is about 560 teaspoons for the average 70-kg person, much higher than the normally consumed quantities) [11]; even then, the relative risk for bladder cancer is merely 1.3 (95% CI 0.9–2.1) [10]. After all, these sweeteners had to be approved as safe by the U.S. FDA before they were marketed [6]. The American Dietetic Association states that artificial sweeteners are safe to use overall. The AHA’s position favors their use for diabetics and people on a weight loss diet.

Of note, the benefits of artificial sweeteners in adults have not been reproduced in pediatric populations [12], other than for diabetics; in fact, the American Academy of Pediatrics recommends that such products should not form a significant part of a child’s diet [13].

In summary, research has failed to prove any detrimental effects of artificial sweeteners; on the contrary, many benefits have been ascertained, the most important of which is weight loss. Obesity, on the other hand, continues on its exponential hike toward the disastrous level, with all associated adverse health consequences. So – if you are deciding between a diet and a regular soda, go with the diet. Add Splenda to your coffee. Or even drink it black! As with everything in life, moderation is key.

Reda Issa is a 3rd year medical student at NYU School of Medicine

Peer reviewed by Neil Shapiro, MD, Editor-In-Chief, Clinical Correlations

Image courtesy of Wikimedia Commons

References:

1. Ulbricht C, Isaac R, Milkin T, et al. An evidence-based systematic review of stevia by the Natural Standard Research Collaboration. Cardiovasc Hematol Agents Med Chem. Apr 2010;8(2):113-127.  http://www.ncbi.nlm.nih.gov/pubmed/20370653

2. Whitehouse CR, Boullata J, McCauley LA. The potential toxicity of artificial sweeteners. AAOHN J. Jun 2008;56(6):251-259; quiz 260-251.  http://www.ncbi.nlm.nih.gov/pubmed/18604921

3. Raben A, Vasilaras TH, Moller AC, Astrup A. Sucrose compared with artificial sweeteners: different effects on ad libitum food intake and body weight after 10 wk of supplementation in overweight subjects. Am J Clin Nutr. Oct 2002;76(4):721-729.  http://www.ncbi.nlm.nih.gov/pubmed/12324283

4. Anton SD, Martin CK, Han H, et al. Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. Appetite. Aug 2010;55(1):37-43.  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2900484/

5. St-Onge MP, Heymsfield SB. Usefulness of artificial sweeteners for body weight control. Nutr Rev. Jun 2003;61(6 Pt 1):219-221.

6. Gardner C, Wylie-Rosett J, Gidding SS, et al. Nonnutritive sweeteners: current use and health perspectives: a scientific statement from the American Heart Association and the American Diabetes Association. Diabetes Care. Aug 2012;35(8):1798-1808.

7. Ma J, Bellon M, Wishart JM, et al. Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects. Am J Physiol Gastrointest Liver Physiol. Apr 2009;296(4):G735-739.

8. Matsukubo T, Takazoe I. Sucrose substitutes and their role in caries prevention. Int Dent J. Jun 2006;56(3):119-130.

9. Goyal SK, Samsher, Goyal RK. Stevia (Stevia rebaudiana) a bio-sweetener: a review. Int J Food Sci Nutr. Feb 2010;61(1):1-10.

10. Weihrauch MR, Diehl V. Artificial sweeteners–do they bear a carcinogenic risk? Ann Oncol. Oct 2004;15(10):1460-1465.

11. Magnuson BA, Burdock GA, Doull J, et al. Aspartame: a safety evaluation based on current use levels, regulations, and toxicological and epidemiological studies. Crit Rev Toxicol. 2007;37(8):629-727.  http://www.ncbi.nlm.nih.gov/pubmed/17828671

12. Brown RJ, de Banate MA, Rother KI. Artificial sweeteners: a systematic review of metabolic effects in youth. Int J Pediatr Obes. Aug 2010;5(4):305-312.

13. Sylvetsky A, Rother KI, Brown R. Artificial sweetener use among children: epidemiology, recommendations, metabolic outcomes, and future directions. Pediatr Clin North Am. Dec 2011;58(6):1467-1480, xi.

Have a Cow? How Recent Studies on Red Meat Consumption Apply to Clinical Practice

April 12, 2013

By Tyler R. McClintock

Faculty Peer Reviewed

“Red Meat Kills.” “Red Meat a Ticket to Early Grave.” “A Hot Dog a Day Raises Risk of Dying.” Such were the headlines circulating in popular press last year when the Annals of Internal Medicine released details of an upcoming article out of Frank Hu’s research group at the Harvard School of Public Health [1-3]. Analyzing long-term prospective data from two large cohort studies, researchers found that individuals who ate a serving of unprocessed red meat each day had a 13% higher risk of mortality during the study period. The numbers were even more grim for processed meats, as a one-serving-per-day increase in such foods as bacon or hot dogs was associated with a 20% increase in mortality risk. Hu and colleagues ultimately concluded that 9.3% of the observed deaths in men and 7.6% of the deaths in women could have been avoided by participants consuming less than 0.5 daily servings (42 g) of red meat [4].

While this study received a great deal of media buzz, it is merely the latest in a long line of studies over the past decade that have tried to better understand how red meat consumption may impact the development of chronic disease. Indeed, our own research group recently set out to answer that same question, although through a different approach: focusing on dietary patterns rather than specific diet elements. Compared to the “single nutrient” or “single food” approach, this analytic method more fully accounts for biochemical interactions between nutrients, as well as interrelationships between dietary components that cause difficulty in distinguishing individual food or nutrient effects. We followed over 11,000 individuals in Bangladesh for nearly 7 years, identifying distinct dietary patterns as well as the associations between these patterns and risk of adverse cardiovascular outcomes. In short, we found that adherence to an animal protein diet increased risk of death from overall cardiovascular disease, especially heart disease. In fact, after stratifying adherence to the animal protein diet into 4 levels, the most adherent group had twice the risk of heart disease mortality compared to the least adherent. While striking, these results inevitably raise the question of what role red meat in particular played in increased mortality, as it was only a component of the more unhealthy diet [5].

The contrasting analytical approaches in these two studies highlight the difficulty in fully understanding how red meat may affect cardiovascular health and mortality. It is believed that adverse outcomes from red meat intake are mediated mainly through the effects of high saturated fat on blood low-density lipoprotein and other cholesterol levels, although high sodium content in processed red meat may also play a role by elevating blood pressure and impairing vascular compliance. Additionally, nitrate preservatives, which are used in processed meats, have been shown in experimental models to reduce insulin secretion, impair glucose tolerance, and promote atherosclerosis [6].

Although multiple studies have shown an association between red meat and cardiovascular disease [7-10], the magnitude of risk is somewhat debatable. In a recent set of meta-analyses, for example, one found equivocal evidence for the influence of meat on cardiovascular disease [11], while another showed consumption of processed red meat, but not unprocessed red meat, to be associated with risk of coronary heart disease [6]. Much of this cloudiness is likely due to inconsistencies across studies in terms of study design, as well as how each defines meat intake and meat types (distinguishing what constitutes “red,” “processed,” or “lean”). Taking all of this into consideration, the best current evidence still seems to indicate that red meat consumption at very high levels conveys increased risk of cardiovascular disease, with processed meats likely increasing that risk. This is similar to what has been observed with respect to type 2 diabetes and colon cancer, as red meat (particularly processed meats) has been linked to a higher risk of both [12-15].

A more complete understanding of healthy eating and advisable intake of red meat is truly of vital importance. Although cardiovascular disease remains the world’s leading cause of death, it has been posited that over 90% of cases may be preventable simply by modifying diet and lifestyle [16-18]. A recent literature review summarized foods that are protective against cardiovascular disease: vegetables, nuts, and monounsaturated fats, as well as Mediterranean, prudent, and high-quality diets [11]. Conversely, as discussed above, current evidence indicates most convincingly that high intake of processed red meats, particularly as part of a Western diet, carries significant risk for increased mortality and adverse cardiovascular outcomes. Many questions, though, remain unanswered–namely, to what extent unprocessed red meat can be grouped with its processed counterpart in terms of health risks, as well as what risk reduction may be possible by substituting lean red meats for either processed or unprocessed meat (which has not yet been addressed in any large prospective study) [19].

Without a full understanding of red meat’s health effects, clinicians are faced with the need to settle for the best available evidence to counsel their patients in need of dietary guidance. The 2010 US Dietary Guidelines for Americans advise for moderation of red meat intake, mainly due to the expected effect of its saturated fat and cholesterol on blood cholesterol [20]. However, with unprocessed and processed red meats having similar levels of saturated fat yet distinctly different clinical outcomes, current dietary recommendations on meat consumption are shown to be based almost solely on the “avoidance of fat” postulate. The resultant dietary recommendations, neither comprehensive nor specific, are justifiably limited by our current level of understanding. Without elucidating the health effects of preservatives in processed meats or potential risk reduction from substitution of lean meats for standard red meat, it is nearly impossible to make more nuanced or quantitative recommendations.

So how does all of this impact the day-to-day practice of a clinician–particularly one in primary care? There will likely never come a day when it is realistic to counsel or expect every patient to avoid red meat completely. In light of recent evidence, though, it is certainly justifiable to recommend moderation, particularly with respect to processed types. Until further research is able to establish hard-and-fast guidelines, qualitative guidance will remain the best evidence-based advice that physicians can hand down. In other words, if a patient’s going to have a cow (or lamb or pork, for that matter), emphasize moderation and recommend that it not be processed.

Tyler R. McClintock is an M.D./M.S. candidate in the Department of Environmental Medicine at New York University School of Medicine. Under the direction of Dr. Yu Chen, his research focuses on how environmental and dietary factors are related to the risk of chronic diseases.

Tyler R. McClintock is a 4th year medical student at NYU School of Medicine

Peer reviewed by Michelle McMacken, MD, Dept. of Medicine (GIM Div.) NYU Langone Medical center

Image courtesy of Wikimedia Commons

References

1. Wanjek C. Red meat a ticket to early grave, Harvard says. Yahoo! Daily News. March 12, 2012. http://article.wn.com/view/2012/03/12/Red_Meat_a_Ticket_to_Early_Grave_Harvard_Says/#/related_news. Accessed May 23, 2012.

2. Dale R. Red meat ‘kills.’ The Sun. March 13, 2012.

3. Ostrow N. A hot dog a day raises risk of dying, Harvard study finds. Bloomberg Businessweek. March 12, 2012. http://www.businessweek.com/news/2012-03-12/a-hot-dog-a-day-raises-risk-of-dying-harvard-study-finds.  Accessed March 23, 2012.

4. Pan A, Sun Q, Bernstein AM, et al. Red meat consumption and mortality: results from 2 prospective cohort studies. Arch Intern Med. 2012;172(7):555-63.

5. Chen Y, McClintock TR, Segers S, et al., Prospective investigation of major dietary patterns and risk of cardiovascular mortality in Bangladesh. Int J Cardiol. 2012 May 3. [Epub ahead of print]

6. Micha R, Wallace SK, Mozaffarian D. Red and processed meat consumption and risk of incident coronary heart disease, stroke, and diabetes mellitus: a systematic review and meta-analysis. Circulation. 2010;121(21):2271-2283.

7. Fraser GE. Associations between diet and cancer, ischemic heart disease, and all-cause mortality in non-Hispanic white California Seventh-day Adventists. Am J Clin Nutr. 1999;70(3 Suppl):532S-538S.

8. Sinha R, Cross AJ, Graubard BI, Leitzmann MF, Schatzkin A. Meat intake and mortality: a prospective study of over half a million people. Arch Intern Med, 2009;169(6):562-571.  http://www.ncbi.nlm.nih.gov/pubmed/19307518

9. Kelemen LE, Kushi LH, Jacobs DR Jr, Cerhan JR. Associations of dietary protein with disease and mortality in a prospective study of postmenopausal women. Am J Epidemiol. 2005;161(3):239-249.

10. Kontogianni MD, Panagiotakos DB, Pitsavos C, Chrysohoou C, Stefanidis C. Relationship between meat intake and the development of acute coronary syndromes: the CARDIO2000 case-control study. Eur J Clin Nutr. 2008;62(2):171-177.

11. Mente A, deKoning L, Shannon HS, Anand SS. A systematic review of the evidence supporting a causal link between dietary factors and coronary heart disease. Arch Intern Med. 2009;169(7):659-669.  http://www.ncbi.nlm.nih.gov/pubmed/19364995

12. McAfee AJ, McSorley EM, Cuskelly GJ, et al. Red meat consumption: an overview of the risks and benefits. Meat Sci. 2010;84(1):1-13.  http://www.ncbi.nlm.nih.gov/pubmed/20374748

13. Fung TT, Schulze M, Manson JE, Willett WC, Hu FB. Dietary patterns, meat intake, and the risk of type 2 diabetes in women. Arch Intern Med. 2004;164(20):2235-2240.

14. Pan A, Sun Q, Bernstein AM, et al. Red meat consumption and risk of type 2 diabetes: 3 cohorts of US adults and an updated meta-analysis. Am J Clin Nutr. 2011;94(4):1088-1096.

15. Larsson SC, Wolk A. Meat consumption and risk of colorectal cancer: a meta-analysis of prospective studies. Int J Cancer. 200;119(11):2657-2664.

16. Lopez AD, Mathers CD. Measuring the global burden of disease and epidemiological transitions: 2002-2030. Ann Trop Med Parasitol. 2006;100(5-6):481-499.

17. Yusuf S, Reddy S, Ounpuu S, Anand S. Global burden of cardiovascular diseases: part I: general considerations, the epidemiologic transition, risk factors, and impact of urbanization. Circulation. 2001;104(22):2746-2753.

18. Ornish D. Dean Ornish on the world’s killer diet. TED Talk. Monterey, CA. February, 2006.

19. Roussell MA, Hill AM, Gaugler TL, et al. Beef in an Optimal Lean Diet study: effects on lipids, lipoproteins, and apolipoproteins. Am J Clin Nutr. 2012;95(1):9-16.  http://www.unboundmedicine.com/washingtonmanual/ub/citation/22170364/Beef_in_an_Optimal_Lean_Diet_study:_effects_on_lipids_lipoproteins_and_apolipoproteins_

20. U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2010. 7th Edition, Washington, DC: U.S. Government Printing Office, December 2010. Page 1 of 4.  http://health.gov/dietaryguidelines/dga2010/dietaryguidelines2010.pdf

Omega-3 Fatty Acids and Atherosclerosis

August 17, 2012

By Michael Malone

Faculty Peer Reviewed

Omega-3 long chain polyunsaturated fatty acids (PUFAs) have been popularized in recent years as beneficial nutrients with cardioprotective effects. Omega-3 PUFAs are so named because of a double bond between the 3rd and 4th carbon of the polycarbon chain. They are “poly-unsaturated” with hydrogen atoms, as their carbon chains contain multiple double bonds. Three omega-3 long chain PUFAs are typically discussed in the context of medical therapy, the first being alpha-linolenic acid (ALA). ALA is an essential precursor omega-3 that is converted by the body into eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).[1] However, this conversion is not very efficient in humans.[2] Omega-3s are best obtained through the diet, but they are available as supplements as well.[1] Omega-3s are common in poultry and most famously found in fish such as salmon, herring, trout, and sardines. ALA is a component of many plant products such as flax seed oil and to a lesser extent canola and soy oils.[3] Increased consumption of omega-3 PUFAs increases their proportion in blood and tissue lipid pools.[4] Serum concentrations of omega-3s can be measured.

Treatment of Hypertriglyceridemia

Omega-3 PUFAs are widely used to treat hypertriglyceridemia, defined as a triglyceride level greater than 150 mg/dL. The NHANES 3 National Health and Nutrition Examination Survey determined that around 35% of men and 25% of women in the US have triglyceride levels over 150 mg/dL. Triglyceride levels greater than 500 mg/dL are associated with an increased risk of pancreatitis.[1] Triglycerides can be lowered through physical exercise, low-calorie diets, and limiting consumption of alcohol. Omega-3 PUFAs can lower triglycerides when used alone or in combination with niacin or fibrates. They can also be used in conjunction with statins, which have a mild ability to reduce triglyceride levels on their own.[3] When omega-3 supplementation was combined with a statin, non-HDL-C levels were reduced much more than on a statin alone. In addition, VLDL-C, triglycerides, and total cholesterol decreased and HDL-C increased–all by more significant amounts than with just a statin alone.[5] Of the 3 omega-3 PUFAs discussed, EPA and DHA have shown the greatest efficacy.[6] The mechanism by which omega-3 PUFAs lower triglycerides is still unknown, but they reduce the hepatic synthesis of VLDLs, which are almost entirely triglycerides, and accelerate lipoprotein lipase, which hydrolyzes triglycerides.[1] With prescription strength omega-3s, triglycerides can be lowered 30-40%.[5] Aggressively lowering LDL-C with statins has been shown to stabilize atherosclerotic plaques.[7]

Clinical Associations

While omega-3 PUFAs are approved for the treatment of hypertriglyceridemia, evidence suggests that they have many other biological activities. Low levels of omega-3 PUFAs have been associated with numerous diseases. One study found that obese children have lower omega-3 concentrations in their serum phospholipids than age-matched lean controls[2] while another found correlations between low omega-3 PUFAs and markers of metabolic syndrome.[8] Low levels of omega-3s were significantly associated with acute coronary syndrome. They were also independently correlated with the presence and degree of lumen occlusion of lipid-rich, atherosclerotic plaques.[9] In other studies, omega-3s were correlated with decreased risk of sudden death and non-fatal myocardial infarction.[4]

Role in Atherosclerotic Disease

The role of omega-3 PUFAs in the treatment of atherosclerosis is not as clear as its role in triglyceride therapy, but there is strong evidence to suggest clinical efficacy. As stated earlier, EPA and DHA have the greatest therapeutic effect and were the omega-3s most often studied. Omega-3 PUFAs influence gene transcription.[10] It is thought that when omega-3s incorporate into the cellular membrane, they disrupt cholesterol rafts, changing the fluidity of cell membranes.[11] This releases endothelial relaxing factors, like nitric oxide, decreasing vascular tone.[12] It has been shown that after 3 months of omega-3 supplementation in obese adolescents with demonstrated vascular inflammation, vasoconstrictive responses and endothelial function improved.[8]

In addition to changing the endothelial response, omega-3 PUFAs seem to modulate the inflammatory response through inhibition of cyclooxygenase-2 (COX-2). While this mechanism is unclear, omega-3 PUFAs incorporate directly into the plaque. Decreased COX-2 activity is associated with decreased release of matrix metalloproteinases (MMPs), which have been implicated in the thinning of the atherosclerotic plaque cap that makes the plaque more prone to rupture.[5] It has been demonstrated that when patients were treated with omega-3s prior to surgery, carotid artery plaques had decreased levels of RNA for MMPs 7,9, and 12.[4] The same study found that in the 3-week treatment period the plaques showed a decreased number of foam cells and T-cells and had less inflammation and increased stability. However, over the short, 3-week presurgical treatment period, there was no change in primary outcome.[4] In another placebo-controlled study, obese adolescents treated with EPA for one year had improved vascular function; reduced inflammation; and decreased levels of lymphocytes, monocytes, TNF-alpha, interleulin-1, and interleukin-6.[8]

COX-2 inhibition affects platelet aggregation as well. EPA has been shown to reduce platelet aggregation and may have a beneficial effect on certain cardiovascular thrombotic disorders.[13] These effects may be enhanced by reduction in serum lipid levels. Elevated postprandial triglycerides were shown to be associated with increased plasminogen activator 1 and factor 7, increasing thrombosis risk and CHD events.[1] By altering lipid levels and regulating inflammatory mediators, endothelial function, inflammation, plaque stability, and platelet aggregation, omega-3 PUFAs have demonstrated a multifaceted, protective effect against atherosclerosis.

The Omega-6/Omega-3 Ratio

Like omega-3s, omega-6 PUFAs are essential fatty acids. Omega-6s have a double bond, but at the 6-carbon location. Arachidonic acid and linoleic acid (not to be confused with the omega-3 ALA) are examples of omega-6 PUFAs. They are commonly found in vegetable oils. The omega-6/omega-3 ratio found in the Western diet is considered high, with a ratio of 15-20/1 rather than the 1/1 found in the diet of many animals and pre-industrial era humans.[10]

Both omega-3s and omega-6s influence gene expression, but in antagonistic ways.[10] While omega-3s inhibit COX-2 products, omega-6s can be metabolized to form eicosanoid metabolic products such as prostaglandins, thromboxanes, leukotrienes, hydroxy fatty acids, and lipoxins.[14] Thus, whereas omega-3s have anti-inflammatory properties, omega-6s are pro-thrombotic and pro-aggretory, causing inflammation, oxidation of LDL, and platelet aggregation. Increasing ratios of omega-6/omega-3 PUFAs in platelet phospholipids have been correlated with an increased death rate from cardiovascular disease.[10] However, many studies have shown that low omega-6 levels are not as clear a predictor of health as high omega-3 levels are, suggesting that adverse health effects associated with high omega-6/omega-3 ratios in the Western diet is more a function of decreased omega-3 intake than the excess consumption of omega-6s.[2]

Lovaza

In addition to omega-3 supplements that are commercially available, there is now an FDA-approved prescription omega-3 supplement available in the US. Lovaza (Pronova BioPharma ASA, Lysaker, Norway) is 38% DHA, 47% EPA, and 17% other fish oils (840 mg of DHA and EPA) and is approved to treat hypertriglyceridemia. Fish-oil supplements commonly have a fishy smell and aftertaste that can be bothersome to some individuals.[6] These pharmacological agents are well tolerated with statins,[5] which are often co-prescribed. There is some concern that omega-3s, due to their anticoagulant effects, may increase the risk of bleeding or of hemorrhagic stroke, especially when combined with other agents like aspirin or warfarin. However, multiple clinical trials do not suggest that a true increased bleeding risk exists with PUFAs, even in combination with other anticoagulants.[6] Lovaza (pronounced “lo-vay-za”) is currently only contraindicated in patients with hypersensitivity to its components and used cautiously in patients allergic to fish or shellfish.

Recommendations

The American Heart Association recommends that patients with or without heart disease eat a variety of fish at least twice a week, preferably fishes like salmon, herring, and trout that are high in omega-3 PUFAs. Patients with heart disease are advised to consume about 1 gram of EPA and DHA daily, preferably from food, but supplements are acceptable after consultation with a physician.[5] There are no clear benefits to a specific omega-6/omega-3 ratio, as long as omega-3 intake is kept high. There are also no significant side effects to increasing omega-3 content in the diet or in a pharmaceutical form.

Conclusion

The idea that disease biology can be fine-tuned by diet is powerful. The potential mechanisms by which omega-3 PUFAs benefit atherosclerosis include lowering triglyceride levels, improving the effects of statin therapy, improving endothelial function, blocking pro-inflammatory pathways, and impairing platelet aggregation though COX-2 inhibition. Omega-3 prophylaxis has already shown therapeutic effects both in patients with prior MI or atherosclerosis and in those at risk for these conditions.

Commentary by Dr. Arthur Schwartzbard

Recent randomized controlled trials of omega-3 supplementation have not consistently demonstrated a reduction in cardiovascular events. To date, these agents look most effective at reducing triglycerides, and Lovaza is FDA approved to reduce triglycerides in patients whose triglycerides exceed 500 mg/dL. These agents are also advised for patients who do not consume at least 1-2 servings of fish weekly. This class has also been useful in patients with HIV dyslipidemia with markedly elevated triglycerides. It is possible that some of the lack of cardiovascular event reduction may be due to the rise in LDL cholesterol that has been noted with many of these agents. A new preparation of fish oil has been recently shown to also reduce LDL, and is currently in phase 3 trials.

Michael Malone is a 3rd year medical student at NYU School of Medicine

Peer reviewed by Dr. Arthur Schwartzbard, MD, Assistant Professor, Department of Medicine, Division of Cardiology, NYU Langone Medical Center

Image courtesy of Wikimedia Commons

References:

1. Bays HE, Tighe AP, Sadovsky R, Davidson MH. Prescription omega-3 fatty acids and their lipid effects: physiologic mechanisms of action and clinical implications. Expert Rev Cardiovasc Ther. 2008;6(3):391-409. http://www.ncbi.nlm.nih.gov/pubmed/18327998

2. Deckelbaum RJ. n-6 and n-3 Fatty acids and atherosclerosis: ratios or amounts? Arterioscler Thromb Vasc Biol. 2010;30(12):2325-2326. http://www.ncbi.nlm.nih.gov/pubmed/21084701

3. O’Keefe JH, Carter MD, Lavie CJ. Primary and secondary prevention of cardiovascular diseases: a practical evidence-based approach. Mayo Clin Proc. 2009;84(8):741-757. http://www.ncbi.nlm.nih.gov/pubmed/19648392

4. Cawood AL, Ding R, Napper FL, et al. Eicosapentaenoic acid (EPA) from highly concentrated n-3 fatty acid ethyl esters is incorporated into advanced atherosclerotic plaques and higher plaque EPA is associated with decreased plaque inflammation and increased stability. Atherosclerosis. 2010;212(1):252-259. http://www.ncbi.nlm.nih.gov/pubmed/20542512

5. Bays HE, McKenney J, Maki KC, Doyle RT, Carter RN, Stein E. Effects of prescription omega-3-acid ethyl esters on non–high-density lipoprotein cholesterol when coadministered with escalating doses of atorvastatin. Mayo Clin Proc. 2010;85(2):122-128. http://www.ncbi.nlm.nih.gov/pubmed/20118387

6. Bays HE. Safety considerations with omega-3 fatty acid therapy. Am J Cardiol. 2007;99(6A):35C-43C. http://www.ncbi.nlm.nih.gov/pubmed/17368277

7. Kadoglou NP, Sailer N, Moumtzouoglou A, Kapelouzou A, Gerasimidis T, Liapis CD. Aggressive lipid-lowering is more effective than moderate lipid-lowering treatment in carotid plaque stabilization. J Vasc Surg. 2010;51(1):114-121. http://www.ncbi.nlm.nih.gov/pubmed/19837545

8. Dangardt F, Osika W, Chen Y, et al. Omega-3 fatty acid supplementation improves vascular function and reduces inflammation in obese adolescents. Atherosclerosis. 2010;212(2):580-585. http://www.ncbi.nlm.nih.gov/pubmed/20727522

9. Amano T, Matsubara T, Uetani T, et al. Impact of omega-3 polyunsaturated fatty acids on coronary plaque instability: an integrated backscatter intravascular ultrasound study. Atherosclerosis. 2011.;218(1):110-116. http://www.ncbi.nlm.nih.gov/pubmed/21684546

10. Simopoulos AP. The omega-6/omega-3 fatty acid ratio, genetic variation, and cardiovascular disease. Asia Pac J Clin Nutr. 2008;17 Suppl 1:131-134. http://www.ncbi.nlm.nih.gov/pubmed/18296320

11. Layne J, Majkova Z, Smart EJ, Toborek M, Hennig B. Caveolae: a regulatory platform for nutritional modulation of inflammatory diseases. J Nutr Biochem. 2011;22(9):807-811. http://www.ncbi.nlm.nih.gov/pubmed/21292468

12. Okuda Y, Kawashima K, Sawada T, et al. Eicosapentaenoic acid enhances nitric oxide production by cultured human endothelial cells. Biochem Biophys Res Commun. 1997;232(2):487-491. http://www.ncbi.nlm.nih.gov/pubmed/9125207

13. Hirai A, Terano T, Hamazaki T, et al. The effects of the oral administration of fish oil concentrate on the release and the metabolism of [14C]arachidonic acid and [14C]eicosapentaenoic acid by human platelets. Thromb Res. 1982;28(3):285-298. http://www.ncbi.nlm.nih.gov/pubmed/6294902

14. Simopoulos AP. The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp Biol Med (Maywood). 2008;233(6):674-688. http://www.ncbi.nlm.nih.gov/pubmed/18408140.

15. American Heart Association. Vitamin and mineral supplements. http://www.heart.org/HEARTORG/GettingHealthy/NutritionCenter/Vitamin-and-Mineral-Supplements_UCM_306033_Article.jsp.  Updated September 24, 2011.  Accessed July 28, 2011.

Is There a Long-Term Mortality Benefit From Bariatric Surgery?

March 8, 2012

By Marc O’Donnell

Faculty Peer Reviewed

Obesity is defined as a body mass index (BMI) of ?30 kg/m2. The rate of obesity in the United States has skyrocketed over the last several decades, becoming a disease of epidemic proportions. According to the Centers for Disease Control and Prevention, in 2009, 32 states had a prevalence of obesity of ?25%, while 9 of these states had a prevalence of ?30%. It has been estimated that the economic costs of treating obesity and its complications, including type 2 diabetes mellitus, heart disease, stroke, osteoarthritis, certain cancers, obstructive sleep apnea, and depression costs the United States approximately $100 billion annually.[1] Over the past several years, bariatric surgery has soared in popularity as an effective weight loss modality. In fact, the NYU Langone Medical Center and Bellevue Hospital Center have been designated Bariatric Surgery Center of Excellence. Although several studies have shown a mortality benefit with bariatric surgery, a 2011 study published in JAMA refutes this claim, posing the question: is there really a long-term mortality benefit with bariatric surgery?

Several studies have demonstrated a relationship between weight loss from bariatric surgery and improved survival when compared to medical management for obesity. The Swedish Obese Subjects study (SOS) was a prospective, matched, surgical interventional trial with 4047 patients (71% female) with an average age of 47 years, and an average follow-up of 10.9 years.[2] After 10 years, the control cohort had an average weight loss of ± 2%, while the surgery cohort had an average weight loss of 14-25%, depending on surgery type, with a decrease in mortality of 21% (absolute risk reduction 1.3%). Importantly, this study was not powered to elucidate the mechanism through which mortality was decreased by bariatric surgery.

A second study, this one a retrospective analysis, had 7925 patients (85% female), with an average age of 39 years, and a mean follow up of 7.9 years.[3] This study demonstrated a 40% decrease in mortality (absolute risk reduction 1.5%) in the surgery cohort, and importantly, this study stratified the mortality benefit. There was a 56% decrease in mortality from coronary artery disease, a 92% decrease in mortality from diabetes, and a 60% decrease in mortality from cancer. Interestingly, death not caused by disease was 58% higher in the surgery cohort. Both of these studies demonstrated a significant decrease in long-term mortality for obese patients who underwent bariatric surgery compared to matched obese patients who were treated with medical management.

The long-term decrease in mortality must be compared with the perioperative mortality rate from bariatric surgery. According to the LABS Consortium, the 30-day mortality rate for bariatric surgery is 0.3% (0% for laparoscopic adjustable gastric banding, 0.2% for laparoscopic Roux-en-Y gastric bypass, and 2.1% for open Roux-en-Y gastric bypass).[4] Considering these findings, the long-term mortality benefit for laparoscopic adjustable gastric banding and laparoscopic Roux-en-Y gastric bypass exceeds the perioperative mortality for both operations, while the perioperative mortality for open Roux-en-Y gastric bypass surpasses the long-term mortality benefit from the weight loss accomplished by the surgery. Open bariatric surgery, however, constitutes less than 10% of all bariatric surgery performed in the United States.[5] Perioperative mortality rate must be carefully considered when recommending bariatric surgery to a patient.

While the aforementioned studies have demonstrated a 21-40% reduction in long-term mortality after bariatric surgery compared to matched controls prescribed medical management for obesity, a 2011 study in JAMA by Maciejewski and colleagues did not demonstrate a statistically-significant mortality benefit for bariatric surgery. The study was a retrospective analysis of 1695 patients (74% male) in Veterans Affairs medical centers, with an average age of 50 years, and an average follow-up of 6.7 years.[6] With propensity-matched controls and after Cox regression, bariatric surgery was not found to have a decreased long-term mortality rate when compared to medical management for obesity (hazard ratio of 0.83, 95% confidence interval of 0.61-1.14). The study’s authors claim that their surgery cohort was at high risk because the majority of patients were men, at an older average age, and with higher average BMI than previous studies with a similar endpoint. In the 2 previously examined studies, the majority of patients were female, with a younger average age, and lower average BMI. Also, the BMI of the patients in the VA surgery group was 47.4 kg/m2 compared to 42.0 kg/m2 in the nonsurgical controls. The lack of mortality benefit found with bariatric surgery in such a high-risk cohort may be due to the advanced comorbid illnesses that the patients already had due to obesity, indicating that for older and sicker patients, bariatric surgery does not confer a mortality benefit; the benefit is found in younger and healthier patients who have yet to experience end-organ dysfunction from obesity and its related complications.

Historically, bariatric surgery has been associated with improvements in quality of life, morbidity, and, most importantly, mortality. It is essential to compare the perioperative mortality rate with the long-term improvement in mortality conferred by bariatric surgery to ultimately determine the mortality benefit of surgery. Recent data, however, have shown no mortality benefit for bariatric surgery in high-risk obese patients. The lack of mortality benefit can likely be explained by irreversible end-organ damage, which could have been prevented had surgery been done at a younger age. This suggests that a more careful examination of comorbid illnesses and end-organ dysfunction should be performed before recommending patients for bariatric surgery in order to more carefully select those patients who will have a mortality benefit from surgery. More studies on the long-term risks and benefits of bariatric surgery are sure to be published, improving the quality of evidence assessing the long-term implications of bariatric surgery.[7]

Marc O’Donnell is a 4th year student at NYU School of Medicine

Peer reviewed by Manish Parikh, MD, Assistant Professor, Department of Surgery, NYU Bariatric Surgery Associates

Image courtesy of Wikimedia Commons

References

1. Ludwig DS, Pollack HA. Obesity and the economy: from crisis to opportunity. JAMA. 2009;301(5):533-535. http://jama.ama-assn.org/content/301/5/533.full

2. Sjöström L, Narbro K, Sjöström CD, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357(8):741-752. http://www.nejm.org/doi/full/10.1056/NEJMoa066254#t=articleTop

3. Adams TD, Gress RE, Smith SC, et al. Long-term mortality after gastric bypass surgery. N Engl J Med. 2007;357(8):753-761. http://www.nejm.org/doi/full/10.1056/NEJMoa066603#t=articleTop

4. Longitudinal Assessment of Bariatric Surgery (LABS) Consortium. Flum DR, Belle SH, King WC, et al. Perioperative safety in the longitudinal assessment of bariatric surgery. N Engl J Med. 2009;361(5):445-454. http://www.nejm.org/doi/full/10.1056/NEJMoa0901836#t=articleTop

5. DeMaria EJ, Pate V, Warthen M, Winegar DA. Baseline data from American Society for Metabolic and Bariatric Surgery-designated Bariatric Surgery Centers of Excellence using the Bariatric Outcomes Longitudinal Database. Surg Obes Relat Dis. 2010;6(4):347-355. http://www.sciencedirect.com/science/article/pii/S1550728909007709

6. Maciejewski ML, Livingston EH, Smith VA, et al. Survival among high-risk patients after bariatric surgery. JAMA. 2011;305(23):2419-2426. http://jama.ama-assn.org/content/305/23/2419.full

7. Padwal R, Klarenbach S, Wiebe N, et al. Bariatric surgery: a systematic review of the clinical and economic evidence. J Gen Intern Med. 2011;26(10):1183-1194. http://www.springerlink.com/content/k48h0686338u7012/