Selenium and Bariatric Surgery

by Jacqueline Jacques, ND

Dr. Jacques is Chief of Scientific Affairs, Bariatric Advantage, Catalina Lifesciences, Inc., Irvine, California.

Introduction
Selenium, an essential trace mineral, is an important component of many enzymes and proteins in the human body. Selenium-dependant compounds act as antioxidants, regulate thyroid function, and play significant roles in immune function, detoxification, and muscle metabolism.

Selenium has garnered much recent attention for its potential role in cancer prevention. Several large studies looking at selenium intake and cancer risk have shown an association with rates of occurrence for specific cancers.

These studies included a 1996 report published in JAMA that found that selenium at three times the current recommended daily allowance (RDA) led to 63-percent fewer cases of prostate cancer, 58-percent fewer cases of rectal cancer, 47-percent fewer cases of lung cancer, and an overall 50-percent reduction in total cancer deaths.1 Numerous studies have since demonstrated similar results. Based on the totality of these findings, the FDA recently allowed a qualified health claim for selenium and cancer prevention2—a rarity for the FDA for any nutrient.

Sources and Absorption
Selenium in the diet comes in two primary forms: selenoproteins that occur naturally in plant and animal products and sodium selenite that is fed to animals in areas with selenium-poor soil or is found in some dietary supplements. Sodium selenate is also used in nutritional products. Selenium is generally well absorbed, although it is believed that selenomethione is the best-absorbed form. Selenomethionine has been demonstrated to be up to 90 percent bioavailable in studies of absorption.3 Most absorption of selenium occurs in the duodenum; some can occur in the jejunum and ileum. Absorption appears to be enhanced by the presence of other antioxidants, such as vitamins E and C. Mercury and other heavy metals inhibit absorption.

Once absorbed, selenium is transported by low and very low density lipoproteins (LDL and VLDL). It is then incorporated into the selenoproteins by a process that is not fully understood. Selenium can be stored in selenoproteins and muscle, as well as in some organs, such as the liver, kidney, and pancreas. The body stores about 15 milligrams of selenium in total.

Deficiency—General
Selenium deficiency is thought to be rare in the general population. The mineral is widespread in animal products, especially organ meats and seafood. Plants contain varying amounts of selenium depending on where they are grown. This is because plants do not require selenium, but will absorb it from soil if it is present. Before animal feeds were selenium-enriched, the amount of selenium in meats varied much more depending on the meat’s origin. Most feeds now contain selenium, which largely makes up for regional variability.

As deficiency is uncommon, a typical clinical presentation is not really established. In areas where there is selenium-poor soil and people are largely restricted to local food sources, there are endemic conditions related to selenium deficiency. Keshen and Kashin-Beck disease occur primarily in rural parts of Asia and affect the heart and the connective tissue, respectively.

Keshan disease is actually thought to be a viral condition that selenium deficiency creates susceptibility to, whereas Kashin-Beck disease appears to be due to the combined influences if selenium and iodine deficiency with environmental factors. The clearest picture we have of isolated selenium deficiency comes from symptoms that arise from the use of selenium-deficient total parenteral nutrition (TPN).4 These symptoms include myopathy, cardiomyopathy, arrhythmia, and muscle wasting. Muscle weakness and pain is more commonly reported in the legs and is more proximal than distal. Symptoms could also include impaired immunity, low thyroid function, loss of skin and hair pigmentation, and whitened nail beds.5 Loss of skin pigmentation has been reported as severe in case reports, manifesting as pseudoalbinism.6 Progressive encephalopathy has also been reported.7 There are also sporadic case reports of encephalopathy in children with selenium deficiency due to TPN. Reported symptoms include dysarthria (slurred, distorted speech, difficulty swallowing), spasticity, weakness, rigidity, clenched fists, and flexion (decorticate posturing).

Deficiency in Obesity
Selenium is part of the group of nutrients classified as antioxidants. Antioxidants are nutrients or chemicals that neutralize free radicals in the body. Free radicals are molecules containing unstable oxygen or nitrogen species that can damage cell membranes, DNA, and other molecular structures. Damage from free radicals is linked to aging, cancer, heart disease, and other health problems. Dietary antioxidants are critical for maintaining and replenishing the overall antioxidant capacity of the body. In addition to selenium, they include many essential nutrients like vitamins C, A, E, and zinc, as well as phytochemicals like carotenoids, anthyocyanins, flavonoids, and catechins.

As scientists have begun to explore the links between obesity, cardiovascular disease, and metabolic syndrome, antioxidants have been studied as a possible link in the pathophysiological chain. When antioxidant status is low in the human body, this creates a condition known as oxidative stress. There is an established inverse relationship between oxidative stress and cardiovascular diseases, including angina,8 atherosclerosis,9 and coronary artery disease.10 Low antioxidant status is also directly linked to oxidation of LDL cholesterol, which is thought to be a necessary step in the development of atherosclerotic plaques.

Metabolic syndrome is a condition defined by a cluster of symptoms, including abdominal obesity, hypertension, insulin resistance, dyslipidemia, inflammation, and increased thrombic tendencies. While the definition includes the constellation of problems, obesity is thought to be a major factor in the development of the condition. Insulin-resistant individuals often have an increase in advanced glycation end-products (AGEs). AGEs act as free radicals, thus further stressing the endogenous antioxidant system. This, in turn, may create an even greater conditional need for antioxidants in these individuals.

Oxidative stress is generally more prevalent in obesity for these reasons and others that are not fully understood. It is likely that the cause for low antioxidant status in obesity is multifold, including additional causes, such as increased demand (due to increased free radical activity), fat sequestering of key antioxidant nutrients (such as vitamins E and A), and possibly low intake.

Preoperative Deficiency
Two studies have found selenium deficiency in patients preparing for bariatric surgery.
A 2006 study by Madan, et al., comparing preoperative vitamin and trace mineral levels to levels at one year postoperative, found a 58-percent rate of selenium deficiency prior to surgery.11

Also in 2006, a study presented at the annual meeting of the American Society of Metabolic and Bariatric Surgery by Urban, et al.,12 looked at pre- and postoperative levels of selenium in patients undergoing either a Roux-en-Y gastric bypass (RNY) or a laparoscopic adjustable gastric banding (LAGB). Six and a half percent of preoperative patients in this study presented with low selenium.

Postoperative Surgery
Until recently, there was almost no documented data on selenium deficiency and bariatric surgery. A 1988 study examined selenium and zinc status in jejunoileal bypass (JIB) patients and found significantly reduced selenium status in the 18 patients studied compared to non-operative controls.13 In 2006, a single case report of severe selenium deficiency secondary to bilio-pancreatic diversion (BPD) was described in the literature. The patient, who was two years postoperative, was admitted to the hospital with protein-calorie malnutrition, and was placed on TPN that was devoid of selenium (as well as other nutrients). After two weeks, the patient developed acute severe heart failure, eventually diagnosed as selenium-deficient dilated cardiomyopathy. Based on the history given, it is more likely that this deficiency resulted from the TPN and not from the procedure; however, it underscores the importance of assuring that bariatric surgery patients in need of TPN receive the appropriate micronutrition.

The two studies discussed under preoperative nutrition both compared levels of selenium before surgery to those after surgery. In the study by Madan, at 12 months following gastric bypass, selenium levels had significantly improved with only three percent of patients having low lab values at follow-up. All patients in this study were instructed to take a chewable multivitamin three times daily, and the authors reported a high level of compliance in patients returning for follow-up labs. In the study by Urban, 15.2 percent of gastric bypass patients and 28.6 percent of LAGB patients were found to be selenium-deficient at one year. Researchers did not report on the specific supplementation being given to patients or on compliance. What is interesting here is that the higher rate of deficiency was found in the restrictive procedure, indicating that this is more likely to be an issue of intake from food or supplements and not from malabsorption. It is relatively common to not recommend vitamins to LAGB patients, including children’s chewable vitamins, many of which do not include selenium in their formulations. Further, we may also be looking at a difference based on the rate of resolution of diabetes/metabolic syndrome. As these conditions resolve much more rapidly with RNY, these patients may have less deficiency because there is less demand on their antioxidant systems.

Lab Evaluation
Plasma and serum selenium concentrations are only reflective of recent intake and tell little about long-term or functional status. Selenium levels can also be measured in red blood cells (RBCs), which would reflect a three-month period. For functional assessment, measurement of glutathione peroxidase activity is the best-accepted method. This can be assessed in platelets, RBCs, or plasma. RBC levels have the longest half-life and are probably the preferred medium. Platelet levels are also well accepted.

Discussion
Selenium deficiency is generally poorly understood. When we examine our current knowledge relative to bariatric surgery, what can we say at this point? When we look at the literature discussed above, the only documented symptomatic deficiency presented was the single case report in the BPD patient on TPN. This was also the only case in which glutathione peroxidase levels were measured. So an important question might be: For asymptomatic patients with low serum levels, what should we be thinking about? As Urban, et al., point out in their study comparing RNY and LAGB patients, this appears potentially to be more of an issue of intake versus malabsorption. Madan’s data—showing greatly improved selenium status in RNY patients with high vitamin compliance—would seem to support this as well. Keeping in mind that serum selenium levels are primarily reflective of short-term intake, this is probably the most accurate thing we can say at this time, although the data is clearly insufficient to draw any conclusions.

You might also ask: If patients are asymptomatic, should we treat them? If you are running tests for selenium and finding low lab values, it is probably a good idea to look at dietary and supplemental intake and see how they can be improved. The recommended daily allowance (RDA) for selenium is 55mcg, and the daily value (DV) is 70mcg, so patients should be getting at least somewhere in this range on a daily basis. A good multivitamin should supply this amount, although surprisingly many popular children’s vitamins do not have any selenium at all. Selenium-rich foods include Brazil nuts, seafood (especially shellfish), meat, milk, and brown rice. For symptomatic deficiency, therapeutic doses are usually around 200mg.

Selenium, like most trace elements, can be toxic if too much is taken. The Institute of Medicine sets 400mg as the Upper Limit based on the ability of chronic toxicity to develop at that level. However, studies of healthy men fed diets supplemented with 300mg of selenium developed clinical hypothyroidism and weight gain after only 99 days.14 Thus, giving excessive selenium in asymptomatic patients is not advised.

Should you even be testing for selenium in your patients? Nutritional testing can be costly, and while esoteric tests of this kind conducted under study protocols teach us a great deal, there is no reason at this time to consider selenium as a routine test in bariatric surgery patients.

References
1. Clark L, Combs GF, Turnbull BW, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. JAMA 1996;276(24):1957–63.
2. Allowable claim per FDA letter dated February 11, 2003: “Selenium may reduce the risk of certain cancers. Some scientific evidence suggests that consumption of selenium may reduce the risk of certain forms of cancer. However, FDA has determined that this evidence is limited and not conclusive.”
3. Food and Nutrition Board, Institute of Medicine. Selenium. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. Washington D.C.: National Academy Press; 2000:284–324.
4. Gramm HJ, Kopf A, Bratter P. The necessity of selenium substitution in total parenteral nutrition and artificial alimentation. J Trace Elem Med Biol 1995;9(1):1–12.
5. Nakamura N, Nokura K, et al. Selenium Deficiency in a Patient with Crohn’s Disease Receiving Long-term Total Parenteral Nutrition. Internal Medicine 2003:42:154–57.
6. Vinton NE, Dahlstrom KA, et al. Macrocytosis and pseudoalbinism: Manifestations of selenium deficiency. J Pediatr 1987;111(5):711–7.
7. Kawakubo K, Iida M, Matsumoto T, et al. Progressive encephalopathy in a Crohn’s disease patient on long-term total parenteral nutrition: Possible relationship to selenium deficiency. Postgrad Med J 1994;70(821):215–9.
8. Riemersma RA, Wood DA, Macintyre CCH, et al. Risk of angina pectoris and plasma concentrations of vitamins A, C, and E, and carotene. Lancet 1991;337:1–5.
9. Diaz MN, Frei B, Vita JA, Keaney JF. Antioxidants and atherosclerotic heart disease. N Engl J Med 1997;337:408–15.
10. Stampfer MJ, Hennekens CH, Manson JE, et al. Vitamin E consumption and the risk of coronary disease in women. N Engl J Med 1993;328:1444–8.
11. Madan AK, Orth WS, Tichansky DS, Ternovits CA. Vitamin and trace mineral levels after laparoscopic gastric bypass. Obes Surg 2006;16(5):603–6.
12. Urban M, Daud A, Digiorgi MF, et al. Zinc and selenium deficiency after weight loss surgery. SOARD 2006;2(3):354.
13. Gjorup I, Gjorup T, Andersen B. Serum selenium and zinc concentrations in morbid obesity. Comparison of controls and patients with jejunoileal bypass. Scand J Gastroenterol 1988;23(10):1250–2.
14. Hawkes WC, Keim NL. Dietary selenium intake modulates thyroid hormone and energy metabolism in men. J Nutr 2003;133(11):3443–8.

Category: Nutritional Considerations in the Bariatric Patient, Past Articles