You may view student ratings of some of the chiropractic colleges, but at this time only a few colleges are rated.

The following article addresses the key considerations when choosing your chiropractic institution.

Key Tenets

Philosophy

Probably the biggest defining factor between most of the schools.  Some schools focus heavily, or even exclusively on the philosophy. So what do I mean by philosophy? Philosophy is the theory as to why chiropractic works and thus how to treat your patients. At times it can almost become dogmatic in its approach.

The type of philosophy can vary dramatically too. Some schools are known as ‘mixer’ colleges. At these institutions chiropractic is seen as on of the many tools a chiropractor can provide to heal their patients, along with nutrition, modalities (Electrical stimulation, ultrasound, cold laser, etc.), soft tissue and muscle work, and exercises. Other schools that are more ‘traditional’, primarily focus on the manipulation of spine.

Schools that focus highly on philosophy include… Life College and Sherman College.

Science

To diagnose properly, and recognize diseases outside of a Chiropractor’s realm, one needs extensive teaching in science. This includes anatomy, physiology, physics, pathophysiology, kinesiology, chemisty, and so forth. Some chiropractic schools excel in this department, competing with medical colleges in the content taught. Others offer a more basic science education, often associated with their greater emphasis on the philosophy.

Schools that focus highly on science include… National University of Health Sciences, New York Chiropractic College, and Western States.

Art

Adjusting techniques and patient interactions. This is really the bread and butter of a chiropractor, and of course every school is going to tell you their technique program is the best. In all reality, pretty much all the schools provide a roughly equal education, and its really up to the student to take it as far as possible.

The schools however do teach different techniques, so for example if your doctor uses Toggle on you, and you love it, a school like NYCC which doesn’t teach it in its core curriculum may be a poor choice. Make sure when talking with school representatives to find out what techniques they include in their core teachings.

Business

The unfortunate reality is that chiropractic is ultimately a business, and unless you’re a trust fund baby, if you want to eat you better learn how to run and advertise an office. The importance of a good business education is really dependent on your plans post chiropractic school. If you plan on going solo, you need all the education you can get or your odds of failure go up tremendously. If you plan on being an associate, most likely you’ll get plenty of training in that department.

A key item to ask the college representative is how you obtain patients when you enter your clinical trials. Some colleges will provide the patients, others make it your responsibility.

Schools that focus highly on business include… Parker College.

Location

Ok, ok, I know I played down this factor, but it is important. If its located somewhere that really isn’t you, you’ll be miserable and education will suffer because of it. For the county bumpkin:  New York Chiropractic College and Palmer College. For the city slicker… National University of Health Sciences and Life University. For the beach bum…  Palmer College Florida for example.

In Summary

At the end of the day, all of the colleges only have so many hours to afford in any type of class, and thus ‘best’ college really depends on what you are looking for. But don’t leave it all to location.

Is the risk real?

Chiropractic is the largest alternative medicine profession in the United States, and probably the most debated. Undeniably, the hottest debated topic concerning chiropractic is stroke risk. But are you really flirting with death when you visit a Chiropractor? This article, written with common argument headers, attempts to discern if cervical manipulation is a risky treatment, especially when compared with other popular treatment options.

Neck manipulation dissects the vertebral basilar artery leading to stroke…

The most basic argument that needs to be proven for anti-manipulation activists to have a ground to stand on is whether a neck manipulation has the physical means to cause a stroke. Detractors claim that forceful manipulation of the neck dissects the vertebral basilar artery, which passes through the atlas (top neck bone/vertebrae) before it enters the skull. This dissection is caused by either the physical stretching of the artery or by its contact with the bone. This very idea is actually what many chiropractic colleges teach, but its reality becomes doubtful when viewing the research.

A series of studies were conducted to determine how much force and stretch the vertebral artery can sustain before it fails. Symons study, using cadavers, applied multi-directional forces to the the neck while measuring its effects on the vertebral artery. It was determined that the arteries could withstand stretching between 132% and 160% their normal length before failing. The study was repeated utilizing cervical manipulation techniques, and it was found that the vertebral arteries were maximally stretched by 6.2% their resting length (Symons 2002). Even more interesting was although cervical manipulation is often perceived as inducing large amounts of neck rotation, due to its controlled nature the vertebral arteries are actually stretched less than in normal neck range of motion (12.5% max).

The idea that the problem is a disruption of blood flow is also not supported by the literature. Licht et al performed a study in which vascular flow was monitored pre and post adjustment. There was no difference between either groups.

Further proof that cervical manipulation is unlikely to cause vertebral artery dissection can be seen when you compare it to motor vehicle accidents. Although MVAs are a traumatic event linked to many health complications, stroke is not one of the commonly associated events. Studies measuring the force of an MVA on the neck demonstrated peak forces of about 241 Newtons, while studies focusing on forces of neck manipulation show a maximal force of 93 newtons. On top of that, rotatory forces maxed out at only 50 newtons (Haneline 2005) If the greater force seen in an MVA fails to cause strokes, why would a lower force adjustment cause it?

The number one cause of cervical arterial dissections are idiopathic. In other words, doctors have no idea what has caused it and thus it is considered spontaneous and unpredictable. Spontaneous Vertebral artery dissections occur at a frequency of about 1 per 100,000 people in the general public (Haneline 2007). Which is an eye opening statistic when the chiropractic population experiencing a CAD is believed to be about 1 per 100,000 patient, which would mean chiropractic patients are at no greater risk for stroke than the general population.

This neurology study showed that stroke occurred after adjustments…

Probably the most cited research article by neck manipulation detractors is a Canadian population based case-study by Rothwell (2001). The study demonstrated that patients who had a stroke were 5 times more likely to have seen a chiropractor within the previous week, and is a perfect example of correlation, but not causation. One key variable that the study had failed to address was why the stroke patients had visited a chiropractor in the first place. Unfortunately, many of the symptoms of a stroke are the same as the reasons people see Chiropractors: neck pain, headaches, tingling or numbness in the extremities, and occasionally mild dizziness. Strokes also present with more pathognomonic warning signs, but these signs tend to be rare, such as severe dizziness, nausea, vomiting, abnormal gait, trouble speaking, and loss of vision in one of the eyes (AHA 2009). Also, the demographic group most prone to idiopathic strokes are also the Chiropractors biggest patient base, young to middle aged women with no major health concerns.

Anti-Chiropractic bias also appears to taint many cervical adjustment articles. One key example is an article in the Journal of Neurology entitled “Vertebral Artery Dissections after chiropractic neck manipulation in Germany over three years.” Not only was this study, like Rothwell’s, a purely correlative study with no modification for external variables such as presentation, but the study’s title unfairly targets Chiropractors. Analysis of the data shows that 11% of all strokes recorded were performed by chiropractors, while 50% were performed by orthopedic surgeons and 14% by physical therapists (Rueter 2006). Even though the manipulations by MD’s and PT’s had a higher rate of associated stroke, it is the Chiropractic Adjustment that is dangerous.

Finally, recent reports have shown that an elevated incidence of stroke is seen equally in Chiropractic and medical physician offices (Cassidy 2008); once again supporting the theory that patients are presenting with a stroke, and not that DC’s, or MD’s for that matter are causing a stroke.

A signature isn't enough.

Chiropractors don’t inform patients of the risk…

A rare valid argument. Some chiropractors do not inform patients that there is a risk for stroke, others do have it written in their informed consents but fail to verbally state it (who reads those things anyway?) Legally, Chiropractors are not required to inform patients of the risk for stroke because the odds of one are so low. However, informed consent should not merely be a Risk Ratio, but also a Perceived Risk-Ratio (Ziker 2003). Since the risk of stroke is perceived in chiropractic, the doctors should address it, regardless if the risk is real or not.

I read a case study in which the person had a stroke…

We’ve all seen the case reports or the news stories where someone immediately suffered a stroke right after receiving an adjustment. However why the stroke happens presents us with three options.

1. The doctor’s impulse caused a stroke in an otherwise healthy patient. Not possible, as the prior argument has already established.
2. The patient was a stroke waiting to happen. The adjustment was the final straw. This is the most likely situation. As noted prior many patients who are currently in a stroke status may visit a chiropractor for their symptoms. In this case, any minute trauma may either mobilize a clot or cause the artery to dissect. Whether or not the doctor should be held responsible in this situation really depends on the circumstances. An unfortunate reality is that there are currently no known reliable orthopedic or neurological tests for stroke (although the Newton Neurological Battery looks promising). The best tool a doctor has is a thorough complaint history and the presentation of the pathognomonic signs. When a patient presents with the hallmark red flags, the doctor should send the patient to the hospital immediately.
3. The patient suffers an idiopathic stroke unrelated to the adjustment. Pure dumb luck.

The risk outweighs the benefits…

The rate of stroke associated with cervical manipulation varies widely among the literature. Figures place the occurrence at as often as 1 in 400,000 cervical adjustments (Dvorak, 1985) and up to 1 in 5,850,000 cervical adjustments (Hosek, 1981). Currently the generally accepted odds are about 1 in 1,000,000 to 3,000,000 cervical adjustments (Lauretti 1997); the RAND report, which is the document most federal mandates concerning chiropractic effectiveness is based upon, also puts the risk at about 1 in a million. However, there is an inherent problem within all manipulation risk studies, in that they are based on correlations, and none are experimental or direct causation models. One of the oldest tenets of research is that correlation does not equal causation. For example, there are an increase in armed robberies when ice cream sales increase. Of course its ludicrous to say that ice cream cause robberies, and instead there must be other variables in play. In this case, robberies increase during the summer, which is the same time ice cream sales increase.

For the sake of our argument, we will be using the 1 in 1,000,000 estimate, and I will compare it to the serious risks associated with other common treatments for neck pain and neck related conditions, all of which are considered safe alternatives. Serious risks are defined as those requiring medical attention.

No treatment is without its risk.

NSAIDS (Aspirin, Aleve, Ibuprofen, etc…) One key meta-analysis using 18 studies published between 1990 and 1999 assessed the risk of life threating upper gastric complications (bleeding, perforation, and hospitalization) when confounding variables such as age, previous complaints, and other medications were removed. It was found that individuals taking NSAIDs (ibuprofen, naproxen “Aleve”, etc…) were at a 380% increased risk of a serious upper GI complication (Hernandez 2000). Mathematically, if you take NSAIDs that equates to the odds of 3500 per million of having a serious upper gastrointestinal condition.

Another study focused on the risk of selective inhibitor anti-inflammatory drugs, such as COX-2 which is designed to prevent GI complications, was analyzed for myocardial infarctions (heart attacks). It was found the relative risk for these drugs are 24% higher than the standard population (Levesque 2005). Adding fuel to the fire, and resulting in the lost license of two major NSAID medications, a Medicare database study after removing most confounding variables, determined that serious cardiovascular complications resulted about 4.1% of the time when taking NSAIDS, including Aspirin (Solomon 2008). What are serious cardiovascular complications? Heart attack, stroke, congestive heart failure, and death. Other studies take these findings ever further claiming drugs such as aspirin, may actually increase the risk of heart attack up to 71%, with an average risk of about 12% (EULAR 2005). Taking the average, this could mean that an additional 570 people suffer NSAID induced heart attacks a year.

Acetaminophen (Tylenol, Excedrin, etc…) The good news with Tylenol is that it is not associated with cardiovascular or gastrointestinal disorders. However, that doesn’t mean its off the hook. Acetaminophen is associated with liver damage, and according to the FDA it is the number 1 cause of acute liver failure in the United States. Usually this is associated with over-dosage, but even minimal usage over the recommend dose is associated with death. This is especially a concern because many people will double or triple their dosages when they are in a lot of pain. Acetaminophen is the cause of 56,000 emergency room visits and 458 deaths a year (FDA 2009). The drug has also been indicated in kidney failure, as an article published in the New England Journal of Medicine determined that regular acetaminophen or aspirin usage put users at 2.5 times the risk for kidney failure, or 250% (Fored 2001). The general public sees about 1550 per million in end stage kidney failure, so if you overuse Tylenol, your odds become 3875 per million. In all fairness, this was a correlative study, not causative. (Coresh 2007)

Neck Surgery Neck and arm pain, tingling, and numbness are often the result of cervical disk herniations, stenosis, and spondylosis; all conditions that are treated with chiropractic. However, if diagnosed in an allopathic office, patients are often recommended for surgery. Although frequently uneventful, surgery obviously has its own risks. One study assessed the complication rate of cervical spine fusion for primarily the noted above conditions (Wang 2007). It was found that 0.83% of all surgeries are associated with a serious complication: Cord injury, artery dissection, infection, cardiovascular comprise, respiratory distress, nerve damage, and death. Therefore, for every 1 million cervical fusion surgeries, 8300 result in serious complications . Once again in all fairness, surgery will often involve the most serious cases and therefore their odds for complication should be elevated.

Physical Therapy & Exercise Serious complications associated with physical therapy are almost as difficult to determine as they are in chiropractic care. Most likely stroke risk matches that of the general population and initial cardiovascular risk may be somewhat increased due to increased physical load, but should decrease over extended treatments due to improving physical health.

Table 1

Conclusions

Compared to the risks associated with the most commonly used treatments for neck pain, it becomes clear that chiropractic neck adjustments are at the very least, comparatively safe. In fact, you are more likely  to die while driving to the doctor’s office in an auto accident than at the hands of the doctor. Furthermore, current research fails to even demonstrate a physiological or anatomical means for a chiropractic adjustment to induce a stroke in healthy patients. Therefore research and debate should begin to move away from attempting to determine if adjustments are safe, and move towards ways to increase the effectiveness of adjustments and improved methods of detecting the small at risk populations.

In closing, a little perspective…

By Kristopher Robert Schuster, D.C., B.S.

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References

1.AmericanHeart Association. Stroke warning signs. Retrieved from http://www.americanheart.org/presenter.jhtml?identifier=4742 on November 20, 2009.
2.American Heart Association. Heart attack and angina statistics. Retrieved from http://www.americanheart.org/presenter.jhtml?identifier=4591 on November 20, 2009. 3.Cassidy JD, Boyle E, Cote P, He Y, Hogg-Johnson S, Silver F, Bondy SJ. Risk of vertebrobasilar stroke and chiropractic care: Results of a population-based case-control and case-crossover study. Spine 2008; 33 (4S):S176-S183.
4.Coresh, J, Selvin, E., Stevens, L.A., et. al. (2007). Prevalence of Chronic Kidney Disease in the United States. J American Medical Association, 298(17), 2038-47.
5.Dvorak J., Orelli F.V. (1985) How dangerous is manipulation to the cervical spine? Manual Med. 2(1), 1–4.
6.European League Against Rheumatism (2005). Retrieved from http://www.theheart.org/article/502645.do on Nov19, 2009.
7.FDA Eyes Acetaminophen Liver Risks (2009). Retrieved from http://www.webmd.com/news/20090528/fda-eyes-acetaminophen-liver-risk on Nov19, 09.
8.Fored, C.M., Ejerblad, E. Lindblad, P., et. al. (2001). Acetaminophen, Asprin, and Chronic Renal Failure. New England Journal of Medicine, 345(25), 1801-1802.
9.Haneline M, Triano J. (2005). Cervical artery dissection. A comparison of highly dynamic mechanisms: manipulation versus motor vehicle collision. J Manipulative Physiol Therapy, 28(1), 57-63.
10.Haneline, M.T., Rosner, A.L. (2007). The etiology of cervical artery dissection. J Chiropractic Medicine, 6(3), 110–20.
11.Hernandez-Diaz, S., Rodriguez, L.A., (2000). Association between nonsterodial anti-inflammatory drugs and upper gastrointestinal bleeding/perforation. An overview of epidemiological studies published in the 1990s. Archives of Internal Medicine, 160, 2093-99.
12.Hernandez-Diaz, S., Rodriguez, L.A., (2002). Incident of serious upper gastrointestinal bleeding/perforation in the general population: review of epidemiologic studies. Journal of Clinical Epidemiology, 55, 157-63.
13.Hosek, R.S., Schram, S.B., Silverman, H., Myers, J.B., Williams, S.E. (1981). Cervical manipulation. J American Medical Association. 245(9), 922.
14.Lauretti, W.J. (1997). Retrieved from http://www.chiro.org/chimages/chiropage/cva-1.html on November 20, 2009.
15.Levesque, L.E., Brophy, J.M., Zhang, B. (2005). The Risk for Myocardial Infarction with Cyclooxygenase-2 Inhibitors: A Population Study of Elderly Adults. Annals of Internal Medicine, 142(7), 481-89.
16.National Safety Council (2004). Odds of dying. http://www.nsc.org/lrs/statinfo/odds.htm
17.Rothwell D.M., Bondy S.J., Williams J.I. (2001). Chiropractic manipulation and stroke: a population-based case-control study. Stroke, 32,1054-60.
18.Rueter U., Hamling M., Kavuk, I. et. al., (2006). Vertebral Artery Dissections after chiropractic neck manipulation in Germany over three years. Retrieved on-line from the J Neurology. 19.Solomon DH, Glynn RJ, Rothman KJ, et al. Subgroup analyses to determine cardiovascular risk associated with nonsteroidal antiinflammatory drugs and coxibs in specific patient groups. Arthritis Rheum (Arthritis Care Res), 59, 1097-104.
20.Symons B.P., Leonard T., Herzog W. (2002). Internal forces sustained by the vertebral artery during spinal manipulative therapy. J Manipulative Physiology and Therapy, 25, 504-10. 21.Wang, M.C., Chan, L., Maiman, D.J. (2007). Complications and mortality associated with cervical spine surgery for degenerative disease in the United States. Spine, 32(3), 342-47.
22.Ziker, D. (2003) Reviving Informed Consent: Using Risk Perception in Clinical Trials. Retrieved from http://www.law.duke.edu/journals/dltr/articles/2003dltr0015.html on November 20, 2009.

That makes it critical, both for patient safety, and our professions reputation to establish methods to detect a stroke patient before any manipulation is provided. In the past, orthopedic tests have been notoriously inaccurate (Drift Test, George’s, etc..) and thus many doctors do not even use them. To date, our best indicator was the patient’s presenting history.

But in addition to a proper history, a new serious of neurological bedside tests finally provide some solid clinical data. Dr. David Newman-Toker recently presented a short series of examinations that proved to be 100% sensitive and 96% specific. Of course further testing needs to be done, as this was a single center study of high risk patients, but regardless it is quite promising.

Newman’s tests included:

1. Strong Horizontal head impulse (a normal patient & a stroke patient’s eyes stays stable during the impulse, an inner ear complication would result in an ‘eye flick’).
2. Nystagmus (Lateral in the same direction as the patient is looking, occurs when the patient looks in either direction)
3. Downward alignment of the eyes when one is rapidly covered and uncovered.

As I research continues on this subject I will update this article.

View the demonstration here… http://www.medscape.com/viewarticle/710698 (you may be required to sign up to view it).

Get the job you want.

As December looms the largest graduating class of the year is getting ready to do just that… graduate. Unfortunately, many of us are facing the reality that getting job post school was a little more difficult than thought. This short article covers a view tips and advice that I have acquired either from others, or via my own experiences.

1. Join Profession Organizations! I can’t stress this one enough. When I was leaving my undergraduate school, Valparaiso University (Great school… I know shameless plug), my Uncle told me that the single best piece of advice he could offer is to join societies. They are absolutely invaluable in establishing contacts and networks. Within a two weeks of joining one of the state chiropractic organizations, I had 4 good interviews lined up.
2. Network with influential doctors. I’ve been regularly shadowing doctors who are board members of their state associations and chiropractic licensure boards, talk about some good contacts.
3. Make a cover letter! Many people forget this critical element to a resume. Its your chance to show your personality and appear different from the pack.
4. Know what you want. Most Doctors want an associate who have goals and drive. In every interview I’ve had I’ve been asked where do you see yourself in 5 years. If you don’t know, your likely not as driven as the Doctor would like, and if you appear unsure in your answer, it will show.
5. Trust your Gut. If red flags go off, don’t take the job, but be polite in your denial; you don’t want to burn any bridges.
6. Send Thank You Letters… Immediately. This shows the doctor that your on the ball, value their time, and really want the job.
7. Spell Check Spell Check Spell Check. If you cant get the detail’s right onn the most important document of you’re life, why would you be anymore caerful with anything else;
8. Be honest. Don’t fudge your resume, or try to be someone you’re not in the interview. Most likely it will show, and if it does not you could find your self in a job you don’t like or are not qualified for.
9. Don’t forget that this is a business. In the interview, show the Doctor how you will help his practice become more successful.
10. Ask lots of questions. Probably my biggest failure. Asking questions shows you are paying attention and are genuinely interested.
11. Post a classified. There are many sites where you can place free ads, such as this website and planet chiropractic.

This article is a growing piece and work in progress. If you have anymore tips please comment, especially if you are a Doctor who has hired in the past.

Swine Flu... its not the pig's fault!

This article is considered a “musing for entertainment” as it is solely based on statistical information (and possibly poor information). The author takes no stance pro or con vaccination.

Whether or not the swine flu vaccine is safe or effective continues to be a debate and is the basis for many families deciding against receiving the vaccine. So here’s an interesting consideration for you all. (But please don’t forget that correlation do not equal causation)

Mongolia has a population of roughly 3,000,000 people. According to the World Health Organization, as of November 4th there has been 6 deaths associated with swine flu. That means that 1 out of every 500,000 Mongolians have died of the swine flu.

The United States has a population of 305,000,000 people. According to the CDC on November 1st, there have been 4000 swine flu related deaths. That means that 1 out of every 76,250 Americans have died of the swine flu.

The kicker… Mongolia does not have the vaccine, the USA does. Is it that Mongolian Hospitals are superior to the US? Hardly… Mongolia’s health-care system is considered the 147th of 190. The USA ranks at 37. Is it because Mongolia is less densely populated? Unlikely. 1/3 of the population lives in a single city alone.

One argument is that that swine flu figures are underreported, and this is likely the case… in non-severe infections. Most people who contract the swine flu are never tested. And the CDC acknowledges this fact and therefore the number of deaths cited above, turns out to be an estimation. The CDC estimates between 2500 and 6000 swine flu deaths. But there is an inherent problem here, when someone dies with flu-like symptoms they are checked for H1N1… even in ‘backwater’ Mongolia (the government has taken a very strict stand with swine flu and checks all cases in a hope to quarantine any possible outbreaks). But I’ll humor their statistics, 2500 deaths means 1 in 122000, or for 6000 deaths means 1 in  50000… again, much greater than Mongolia’s death rate.

Also makes me wonder, why isn’t the CDC reporting the confirmed cases anymore?

Are there extenuating variables involved here, I can guarantee it. But it does make you wonder…

What’s your thoughts? What is wrong with these statistics? Do you plan on getting vaccinated?

This article is considered a “musing for entertainment” as it is solely based on statistical information. The author takes no stance pro or con vaccination.

References

http://www.cdc.gov

http://www.nytimes.com/2009/11/11/health/11flu.html

http://www.photius.com/rankings/who_world_health_ranks.html

Is it really the Egg?

There is no arguing that allergies are a fact of the human existence. You are truly beating the odds if you make it to adulthood without an allergy of some sort, be it pollen, dander, food, or chemical.

What most people do not realize is that allergens have the potential to act synergistically, that is, they multiply each others effects. A study by Johansen et. al. established that when individuals were exposed to two known allergens, instead of adding their effects, the allergic reaction tripled or quadrupled in intensity! Therefore a person who is mildly allergic to yellow 5, may experience an asthmatic reaction when its paired with another common mild allergen, caffeine. Mountain Dew anyone?

Taken a step further, there are some foods or allergens that do not effect us unless you are also exposed to their concomitant allergen. Let me explain. Many people are tested as egg allergic, however they exhibit an allergic reaction to eggs only at certain times of the year. This is likely do to ragweed, as the immunological binding proteins of ragweed closely resemble those of eggs.  This results in a person developing an allergy to eggs, when in reality they are allergic to ragweed, and they may continue to exhibit a reaction up to 6 weeks after ragweed exposure. After that period of time, the individual may be able to eat eggs without issue. This is just one example, but there are many concomitant allergies, such as Birch pollen with Soybeans, apples, hazelnuts, and even a boring piece of celery.

Finally, there are also cross-reactive allergens. Cross-reactive allergens are proteins that are shared among many plant species (and occasionally animal sources, such as dog dander with pork) and exposure to a plant that carries this allergen will now cause you to become allergic to other plants and foods. For example, Apples contain the ‘panallergen’ protein Profilin, but so does birch pollen and peaches. Therefore after experiencing an allergic reaction to the Profilin in an apple, there is the possiblity that the individual will forever also be sensitive to birch pollen and peaches… even if they’ve never come in contact with them before.

Author: Kristopher Schuster

References

Mine Y., and Yang M.(2005). Recent Advances in the Understanding of Egg Allergens: Basic, Industrial, and Clinical Perspectives. Journal of Agricultural and Food Chemistry. 56 (13), pages 4874-4900

Johansen, Skov, Volund, Andersen, MennÉ (1998). British Journal of Dermatology. Allergens in combination have a synergistic effect on the elicitation response: a study of fragrance-sensitized individuals. 139(2), Pages 264 - 270

D. Mittag, S. Vieths, L. Vogel, W. Becker, H. Rihs, A. Helbling, B. Wüthrich, B. Ballmer-Weber. Journal of Allergy and Clinical Immunology, 113(1), Pages 148-154.

Mamikoglu, B. (2005). Beef, Pork, and Milk Allergy (Cross Reactivity With Each Other and Pet Allergies). Otolaryngology – Head and Neck Surgery. Vol. 133(4), Pages 534-537

Schimek EM; Zwolfer B; Briza P; Jahn-Schmid B; Vogel L; Vieths S; Ebner C; Bohle B. (2005). Gastrointestinal digestion of Bet v 1-homologous food allergens destroys their mediator-releasing, but not T cell-activating, capacity. J Allergy Clin Immunol. 116(6), pages 1327-33.

Fernández Rivas M. (2003). Cross-reactivity between fruit and vegetables. Allergol Immunopathol. 31, pages 141-6.

R.van Ree, M.Fernández-Rivas, M.Cuevas, M.van Wijngaarden,, R.Aalberse (1995). Journal of Allergy and Clinical Immunology. 95(3), pages 726-734.

Is the Mercury in Thiomersal Dangerous?

Thiomersal is a preservative that is added to  vaccines to prevent contamination. It contains roughly 49% mercury; therefore a vaccine containing the standard Thiomersal dosage of 50mcg contains 25mcg of mercury. For adults, there are thiomersal free and preservative free vaccines. Thiomersal-free has no thiomersal, while preservative free contains trace amounts, or about .3mcg per dose. Although childhood vaccines can no longer contain thiomersal (as of 1999), the government considers the trace amounts in preservative free versions acceptable, plus, any vaccine that was produced prior may be still be used (assuming its shelf date has not expired).

The FDA set the daily safe limit of mercury at 1.0mcg per kg of bodyweight per day to avoid neurological damage. However, paying attention to the weekly average tends to be a more accurate indicator.

The ultimate question of course is,  “Is it Safe”?

How much mercury can I have “safely”…

• Average American Male, 86.5kg (190lbs) * 0.1 = 8.65 mcg per day= 60.55 mcg a week = 242.2 mcg a month
• Average American Female, 74.5kg (165lbs) * 0.1 = 7.45 mcg per day= 52.15 mcg a week = 208.6 mcg a month
• A Schoolchild, 22.7kg (50lbs) * 0.1 = 2.27 mcg per day =  15.9 mcg a week = 63.6 mcg a month
• 2 Month Old baby 4.54 kg (10lbs) * 0.1 = 0.454 mcg per day =  3.18 mcg a week = 12.72 mcg a month
• Calculate your own mercury risk from the seafood you eat. http://www.gotmercury.org/article.php?list=type&type=75

How much mercury is in Tuna…

• Tuna is considered a safe fish, at least compared to Swordfish or other fatty fish, but it still contains mercury. Chuck light has 0.112ppm of mercury, and white albacore has 0.357ppm
• So if you eat a can of the popular Solid White Albacore Tuna you are consuming… 170.1grams (6 ounces) * 0.357 = 60.726mcg of mercury. That’s the monthly allowance of mercury for children!
• The cheaper chuck light… 170.1grams (6 ounces) * 0.112 = 19.05mcg of mercury.

Regardless of my own opinion on vaccination, this is the take home message.

One can of tuna contains 175x more mercury than a vaccine does, plus tuna contains methylmercury, which of the two forms of mercury is more difficult and takes longer for the body to eliminate. BUT, the body only absorbs between 2 and 38% of mercury in the GI tract, that means at max a can of albacore delivers 20mcg of mercury, or as little as  1.0 mcg of mercury, mattering on a slew of variables (hydration, pH, mineral interaction, etc…).

If you are an adult, avoiding a vaccine only because of the trace amounts of mercury seems unwarranted… your food has more of it (which is a problem in itself… another time…). If you decide thats too risky, then quit eating fish too.

If you are concerned about vaccinating your infant, your fears may be warranted. If the mother has mercury in her system it will be transferred into the breast milk, add that to the 0.3mcg in the vaccine, possible multiple vaccines, and you’re likely well over the limit for an infant. Plus, during this critical stage of neurological development a little extra mercury could have a big effect.

In an attempt to bar my personal bias, this article contains no reference to PRO or AGAINST literature on Thiomersal, only numerical facts on mercury contents in the above mentioned foods & preservatives. This is NOT an article on the safety of vaccines in general, or of other non-mercury related concerns of vaccination.

Author: Kristopher Schuster

References

Clarkson TW, Magos L (2006). “The toxicology of mercury and its chemical compounds”. Crit Rev Toxicol 36 (8): 609–62.

http://www.clu-in.org/contaminantfocus/default.focus/sec/Mercury/cat/Toxicology/

http://www.fda.gov/Food/FoodSafety/Product-SpecificInformation/Seafood/FoodbornePathogensContaminants/Methylmercury/ucm115644.htm

http://www.cdc.gov/FLU/ABOUT/QA/thimerosal.htm

Yess, Norma J. “US Food and Drug Administration Survey of Methyl Mercury in Canned Tuna,” Journal of AOAC International, Vol. 76, No. 1, 1993, pp. 36-38.

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Today I became aware of a bill currently in committee, the Access to Frontline Health Care Act of 2009. This bill strives to amend the current bill from “eligible physicians” to “frontline providers”, as well as specifically designating chiropractors as a frontline provider. As a provider, chiropractors would receive a $50000 loan payment for serving 2 years in an under served area.

I urge all students and doctors alike to sign the chirovoice petition. Or better yet, write your own and send it to your senator!

Is it only good for our eyes?

One of the major avenues of nutrition based research of the past couple decades has been antioxidants’ role in cancer formation. Although observational studies had been very promising, experimental studies continued to fail to find a correlation. Thus experimenters began searching deeper into the subject of antioxidants and came out with a possible solution, Lutein.

Lutein, a highly unstable xanthophyll, has been a rare case in that most experimental data has thus far shown some sort of link between it and cancer, especially in the realm of colon cancer. However, recent supplemental research trials have uncovered Lutein’s possible dangerous effects and have shown that we have only begun to scrape the surface of this potential link.

Basics

In the past couple decades antioxidants have come to the forefront of modern nutrition. Antioxidants are chemical substances that may protect the body’s cells from damage by preventing the harmful effects of free radicals. Free radicals are atoms or groups of atoms that have at least one unpaired electron, which makes them highly reactive. This high reactivity can actually be beneficial by oxidizing and providing energy to an area resulting in bacterial death and controlled cell apoptosis. In excess, however, they produce harmful over-oxidation that can damage cell membranes and cell contents. Antioxidants appear to neutralize free radicals when in an overabundance, thus removing the danger (National Cancer Institute 2005). Although most commonly found in vitamin form, there are many types of antioxidants. Currently the most heavily researched antioxidants are: alpha and beta carotene, lycopene, vitamins A (ascorbic acid), B-6, B-12, C, and E, folic acid, selenium, and Lutein (American Heart Association 2006).

One of the newest antioxidants that received substantial attention in recent years is Lutein. Lutein is a xanthophyll, which is type of plant pigment found in many green leafy vegetables, and is a member of the family of substances known as carotenoids (Emory University Healthcare 2005). With the discovery of Lutein, as sister antioxidant was also discovered, zeaxanthin, which has similar stereochemistry and properties.  Due to zeaxanthin’s mirroring stereochemistry, chemical properties, and difficulty separating from Lutein, unless otherwise noted it should always be assumed that the two are together.

The Configuration of Lutein

To fully understand Lutein, the stereochemistry of this antioxidant is important. The structure of Lutein is characterized by the presence of a hydroxyl group attached to each of the 2 terminal beta-ionone rings in the molecule. This hydroxyl group makes it far more polar than most other antioxidants (Ribaya-Mercado 2004). Additionally, the hydroxyl groups prevent Lutein from being converted into vitamin A as most antioxidants can be. Therefore, this xanthophyll becomes far more hydrophilic and unstable than other carotenoids found in blood and tissues. This high instability leads to a feverish seeking of all available free radicals, making it potentially the most potent antioxidant currently known (Britton 1995). The instability also may lead it to become potentially dangerous, which will be explained in depth later.

Lutein gained great notoriety when it was discovered that the chemical appeared to play a vital role in the prevention of many age related eye disorders including cataracts and AMD (age-related macular degeneration). Additionally, non-laboratory data states that consumers of high levels of Lutein experience less eye fatigue throughout the day, and unlike most antioxidant research, Lutein’s effectiveness in helping to protect our eyes and eyesight has yet to be contested and is universally accepted (National Eye Institute 2004). Thus, it is not uncommon to see many multivitamin supplements that are geared toward the elderly containing Lutein.

How exactly Lutein actually prevents these disorders and aid the eyes is still debated. Currently, the two foremost theories are that like other antioxidants, Lutein neutralizes the free radicals within retinal tissue. The other newer, and increasingly more popular theory, is that Lutein acts as a natural UV protector preventing certain UV wavelengths from reaching the eyes (National Eye Institute 2004).

Where to Get Lutein

Lutein Sources

Humans cannot manufacture carotenoids; therefore, Lutein must be obtained through the diet. Lutein is found largely in plant foods, especially dark-green leafy vegetables. The highest vegetable concentrations can be found in kale, spinach, turnip greens and collards. Other greens are moderate Lutein providers, and these include mustard greens, green peas, summer squash, and broccoli. Citrus fruits have also been found to be good sources of Lutein as compared to most non-leafy foods. Surprisingly, the potentially best source of Lutein, and also the least recognized, is egg yolks. This is due to two reasons: egg yolks have a high concentration of Lutein, and also due to the composition of the lipid matrix of a yolk, the Lutein is extremely bioavailiable (Ribaya-Mercado 2004).

Of course, the easiest way to obtain Lutein would be through supplements. However, since supplement research has been inconsistent in their results, all major government bodies of health do not advise the supplemental use of Lutein. Currently they do advocate its consumption through natural sources. Additionally, increasing research is suggesting that Lutein’s effects are muted without zeaxanthin, which few supplements contain.

Antioxidants and Cancer

As antioxidant research advanced these chemicals became progressively more often deemed as the cure all. If there was a human ailment, antioxidants could solve it. These ailments ranged from stroke, heart and vascular failure, gastric disorders, and nerve transmission. Some scientists, and seemingly the entire media, have even gone as far as to believe that antioxidants could slow down the process of ageing, a modern fountain of youth if you will (National Cancer Institute 2003).

Therefore, it was only a matter of time before antioxidants were suggested to help prevent cancer. Initial observational and epidemiological studies showed promising results in many different forms of cancer. Most studies showed an inverse relation between the consumption of antioxidants and the instance of cancer. The most commonly seen correlation with cancer formation was with the carotenoids. However, experimental studies involving the major carotenoids, including β-carotene have only occasionally showed an inverse correlation with cancer. For example, Hennekens et al. (1996) conducted a 12-year β-carotene lung cancer trial with over 22,000 males. This massive experimental study yielded no statistical difference between the placebo and experimental group, both in the short term and long term. After countless similar results scientists came to two possible conclusions, either supplements cannot properly provide the needed antioxidants, or, the wrong antioxidants are being studied.

Lutein’s Role In Cancer

Since Lutein was already proving to be effective in the battle against eye disorders, scientists turned their focus toward this antioxidant. Researcher’s proposed three ways that Lutein may be able to prevent cancer formation are: radical neutralization, anti-carcinogenic properties, or an immune system boost.

A study conducted by Iannone et al. (1998) was the first to substantially prove that Lutein can neutralize peroxy radicals and help prevent oxidative damage in vitro. In addition, Stahl et al. showed that the combination of Lutein and Lycopene produced the strongest synergistic effect against the existence of radical oxidative damage as compared to any antioxidant by itself or any other antioxidant combination. Thus, the chances of Lutein being able to reduce free radicals in humans is highly probably, but regrettably at this point has yet to be proven in vivo.

Lutein’s second role in cancer prevention is its unique anti-carcinogenic properties. In a couple plant studies conducted by Gonzales de Mejia et al. (1997), Lutein interacted with 1-nitropyrene and aflatoxin B1, both well-known mutagens. Through Lutein’s interaction, a considerable reduction of mutagenic cells was observed. To date, no human model studies have been conducted on this theory for ethical considerations.

Lutein’s final role in cancer prevention is that it boosts our immune system. To accept this theory, it requires the researcher to believe that our bodies constantly present cancerous cells and that our immune system regularly detects and removes these dangerous growths. The idea here is that Lutein improves two areas of the immune system. The first area is an increased activation of mitogens (protein cells that encourage B cell mitosis), cytokines, and antigenic determinates (Park 1999). The second area is an exhibited greater expression of surface molecules on monocytes, resulting in higher antigen detection (Hughes 2000). Although it is still unclear if an immune system boost results in the reduction of cancer, it has been shown that Lutein does boost the immune system (Kim 2000).

As the three theories show, cancer research in regards to Lutein has thus far been quite limited. Even further limited has been site-specific cancer research. To date, Lutein and other antioxidants’ role in breast, gastric, skin, and lung cancer have been largely pioneered by small epidemiologic studies and animal models (Mares-Perlman 2002). However, site-specific research in the area of colon cancer has become quite extensive. Colon cancer is the forth most common form of cancer in both American males and females. Even though the cancer in its early stages is more of an embarrassment or nuisance than dangerous, due to its symptoms that mirror many everyday digestive issues, such as bloating, cramps, and constipation, it often escapes early detection. Due to the heavy concentration of lymph nodes in the area, in later stages colon cancer has a high probability to metastasize, allowing it to suddenly become extremely fatal. Commonly, patients who die of colon cancer die of metastasized cancerous growth on the liver or other critical organs. Currently, the only unabated nutritional link to colon cancer is a diet low in calcium, folic acid, and fiber (National Cancer Institute 2006).

A stained image of actual colon cancer cells.

Colon Cancer – Greensberg

In 1994, Greensberg et al. conducted a major trial testing the effects of antioxidant supplements on colon cancer. Greenberg’s trial was extremely important because it was one of the first non-observational human model experiments on the subject. This large study consisted of 864 patients in four different treatment groups: placebo, Beta-Carotene (25 mg daily), Vitamin C (1 g daily), and Vitamin E (400 mg daily). After one year a complete colonoscopy was performed on each patient, and again at four years. Doctors attempted to locate colorectal adenomas, which are one of the precursors of invasive colon cancer.

The results surprised the research community at the time. It was found that for all of the treatment conditions there was no significant reduction in colorectal adenomas. To make matters worse, not only were the differences between the experimental groups and placebo groups not statistically significant, but the data was nearly identical, suggesting a complete lack of effect even if group sizes where drastically increased. However, sometimes we learn the best from studies that fail to reject the H_naught. Although initially disappointing, Greenberg’s study proved to be pivotal in antioxidant research. Since the study failed to find positive results with the dominant antioxidants of the time, while vegetable observational data had been very promising, researchers were prompted to investigate the other potential antioxidants found in such foods.

Colon Cancer – Slattery

The year 2000 was a pivotal in Lutein cancer research. Slattery et al. performed a large observational study that monitored the risk of colon cancer in 1,993 subjects with first primary incident adenocarcinoma of the colon, which is the actual cancer formation, and 2,410 population-based control subjects. In an effort to determine which antioxidants may reduce colon cancer, Slattery chose to monitor many different poorly researched types including: α-carotene, Lycopene, Lutein, Zeaxanthin, and β-cryptoxanthin. β-carotene was also observed for a comparison to previous research.

The results for every one of the tested antioxidants proved to be non-significant, except for Lutein. Not only was a correlation found, but it was also very strong, proven to the .05 alpha level for males, and .01 alpha level for females. Lutein’s sister antioxidant, Zeaxanthin, also appeared to be beneficial, but only when in tandem with Lutein. Furthermore, the strongest inverse association with Lutien was observed in early onset colon cancer patients. In other words, not only did Lutein reduce the risk of color cancer, but a lack of Lutein consumption was readily seen in patients who were diagnosed with colon cancer before the age of 60.

Colon Cancer – Collins

Of course, Slattery’s research was not the end all, in fact it carried an inherent problem, it was an observational study. The study may have suggested that Lutein was a major player in colon cancer formation, but it failed to establish how this is so.

To answer this question, or at least reduce the possibilities, Collins et al. (1998) conducted an experimental trial in which they measured the amount of DNA damage found in cells and lymphocytes. In their study, participants provided plasma cells and lymphocytes, which were exposed to alpha or beta-carotene, Lutein, or Lycopene in vivo. The results showed that none of the supplements significantly reduced the amount of DNA damage, thus refuting the claim that the antioxidants, Lutein included, does not prevent cancer by protecting against DNA damage by radicals. In addition, since no DNA/antioxidant correlations were found, if the other theories on how Lutein plays a role in cancer formation are also disproved it will suggest that Lutein itself actually does not reduce cancer, but rather it is a biological marker for a third currently unidentified variable.

Lutein’s Dark Side

As promising as Lutein appears to be, the antioxidant is not without its own dangers. In 2004, Raju et al. conducted a critical experimental study with multiple dosage levels of Lutein. Raju et al. procured male F344 rats and fed them standard laboratory rodent chow. A supplement of Lutein was then added to the food of the experimental group rats. The possible levels of dosage were: low dosage (100 ppm or 200ppm), high dosage (1000 ppm or 2000 ppm), or zero ppm, the control group. For the supplementation, by using ppm of the food the rats could eat as much or as little as they desired. Finally, all the rats were injected once weekly for two weeks with 15ml per kilogram of body weight of Azoxymethane, a known potent colonic carcinogen (Sigma-Aldrich 2006).

Formation of a tumor.

After fourteen weeks all the rats were killed for analysis. Researchers attempted to locate aberrant crypt foci formations (ACF), which is the second precursor stage to adenocarcinoma of the colon. This stage was presumably chosen because the first stage, aberrant crypts, can be often be found without stimulation of Azoxymethane and therefore a ceiling effect would likely be observed.

The resulting data from the experiment was quite significant. In the low dosage experiment, 98 of the control rats presented ACF formation. The 100ppm Lutein rats had non-significant data, but at 200 ppm the results were significant (p < .001). Only 71 rats exhibited ACF formation, a 27% inhibition. These results were in line with previous reports. However, the results of the high dosage groups came as a surprise. The control group exhibited 86 ACF positive rats, while the 1000ppm group had 94 ACF positive rats (10% increase, not significant), and the 2000ppm group had a whopping 137 ACF positive rats (59% increase, significant to 0.001). Therefore, Lutein’s effects appeared to be highly dosage dependent, and with each successive dosage above a yet to be established point the danger of the antioxidant becomes progressively greater.

Similar results have been seen in many other recent studies. In one study of prelabour rupture of the membranes preterm (PPROM), high levels of Lutein were seen to be associated with higher prevalence rates (Mathews and Neil 2005). In a far more famous study conducted by Omenn et al. (1996), it was found that the use of antioxidant supplements increased the incidence of lung cancer in smokers. In fact, the longer the participants received the antioxidant supplement, the higher the incidence of lung cancer in comparison to the placebo group. Working with the results of Omenn’s study, a similar trial was conducted for colon cancer. The results showed that in similar fashion to the lung cancer study, healthy individuals showed positive effects from the carotenoids, while smokers and drinkers saw adverse carcinogenic effects in the colon and rectum, suggesting that Lutein’s effects on the body are very dependent on the environment it is placed in (National Cancer Institute 2006). Thus it may be that Lutein’s greatest boon as an antioxidant, its high instability, may be exactly what can make it equally dangerous when placed under the right conditions causing it to become an oxidant.

Conclusions

Lutein appears to have some sort of role in the prevention of cancer. Nevertheless, since the isolation of Lutein in experimental trials have failed to consistently yield a relationship thus far, it appears that Lutein may be acting synergistically with some currently unknown factor. This combination effect could range anywhere from other antioxidants, overall diet, exercise habits, psychology of/with eating, air quality, etc… Thus, it is obvious that more research needs to be conducted on this topic and that experimenters need to analyze prior observational studies, looking specifically for other possible manipulating factors. In addition, most future research should be done experimentally to help isolate the different factors.

Furthermore, three basic questions need to be answered to help us gain a better understanding of the subject. Does Lutein prevent cancer growth? Does a lack of Lutein cause cancer growth? What types of environmental cues cause Lutein to become an oxidant?

Finally, since the effects of large doses of Lutein are not yet understood, and possibly dangerous, supplements should not be taken unless you are a high risk for macular degeneration, in which case no more than 6-20mg a day is recommended. Thus, until concrete evidence is finally reached, the current recommendation of eating a balanced diet with lots of vegetables appears to be the most reasonable and healthy option.

Author: Kristopher Robert Schuster

Works Cited

1. American Heart Association (2006). Antioxidant Vitamins. Retrieved from http://www.americanheart.org/.
2. Britton, G. (1995). Structure and properties of carotenoids in relation to function. The FASEB Journal, 9, 1551 -1558.
3. Collins, A. R., Olmedilla, B., Southon, S., Granado, F. & Duthie, S. J. (1998). Serum carotenoids and oxidative DNA damage in human lymphocytes. Carcinogenesis, 19, 2159-2162.
4. Emory University Healthcare (2005). Lutein. Retrieved February 03, 2006 from http://www.emoryhealthcare.org/.
5. Greenberg, R., Baron, J., Tostenson, T., Freeman, D., Beck, G., & Bond, J. (1994). A clinical trial of antioxidant vitamins to prevent colorectal adenoma. The New England Journal of Medicine, 331(3), 141-147.
6. Gonzales de Mejia, E., Loarca-Pina, G. & Ramox-Gomez, M. (1997) Antimutagenicty of xanthophylls present in Aztec marigold (Tagetes erecta) against 1-nitropyrene. Journal of Mutative Research, 389, 219-226.
7. Hennerkens, C., Buring, J., Manson, J., Stampfer, M., & Rosner, B. (1996). Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. The New England Journal of Medicine, 334(18), 1145-1149.
8. Hughes, D. A., Wright, A.J.A., Finglas, P. M., Polley, A.C.J., Bailey, A. L., Astley, S. B. & Southon, S. (2000) Effects of lycopene and lutein supplementation on the expression of functionally associated surface molecules on blood monocytes from healthy male nonsmokers. Journal of Infectious Disease, 182, S11-S15.
9. Iannone, A., Rota, C., Bergamini, S., Tomasi, A. & Canfield, L. M. (1998) Antioxidant activity of carotenoids: an electron-spin resonance study on beta-carotene and lutein interaction with free radicals generated in a chemical system. J. Biochem. Mol. Toxicol., 12, 299-304.
10. Kim, H. W., Chew, B. P., Wong, T. S., Park, J. S., Weng, B.B.C., Byrne, K. M., Hayek, M. G. & Reinhart, G. A. (2000) Modulation of humoral and cell-mediated immune responses by dietary lutein in cats. Veterinary Immunology and Immunopathology, 73, 331-341.
11. Mares-Perlman, J., Millen, A., Ficek, T., & Hankinson, S. (2002). The Body of Evidence to Support a Protective Role for Lutein and Zeaxanthin in Delaying Chronic Disease. The American Society for Nutritional Sciences, 132, 518-524.
12. Mathews, F., & Neil, A. (2005). Antioxidants and preterm prelababour rupture of the membranes. International Journal of Obstetrics and Gynaecology, 112, 588-594.
13. National Cancer Institute (2006). Understanding colon cancer. Retrieved February 03, 2006 from http://www.cancer.gov/.
14. National Cancer Institute (2005). Antioxidants and Cancer Prevention: Fact Sheet. Retrieved February 03, 2006 from http://www.cancer.gov/.
15. National Cancer Institute (2003). Free radicals: the pros and cons of antioxidants. Retrieved February 03, 2006 from http://www.cancer.gov/.
16. National Eye Institute (2004). Lutein and its Role in Eye Disease Prevention. Retrieved February 03, 2006 from http://www.nei.nih.gov/.
17. Omenn, G., Goodman, G., Thornquist, M., Balmes, J., Cullen, M., Glass, A., Keogh, J., Meysken, F., Valanis, B., Williams, J., Barnhart, S., & Hammar, S. (1996). The effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. New England Journal of Medicine, 334, 1150-1159.
18. Park, J. S., Chew, B. P., Wong, T. S., Zhang, J. & Magnuson, N. S. (1999) Dietary lutein but not astaxanthin or beta-carotene increases pim-1 gene expression in murine lyphocytes. Nutrition of Cancer, 33, 206-212.
19. Raju, J., Swamy, M., Cooma, I., Patlolla, J., Pittman, B., Reddy, B., Steele, V., & Rao, C. (2005). Low doses of b-carotene and lutein inhibit AOM-induced rat colonic ACF formation but high doses augment ACF incidence. International Journal of Cancer, 113, 798 – 802.
20. Ribaya-Mercado, & Blumberg, (2004).  Lutein and zeaxanthin and their potential roles in disease prevention. J Am Coll Nutr., 23, 567-587.
21. Sigma-Aldrich (2006). Azoxymethane. Retrieved rom http://www.sigmaaldrich.com/Area_of_Interest/Life_Science/Cancer_Research/Product_Highlights/Azoxymethane.html.
22. Slattery, M., Benson, J., Curtin, K., Ma, K., Schaeffer, D., & Pott, J. (2000). Carotenoids and colon cancer. American Journal of Clinical Nutrition, 71, 575–82.
23. Stahl, W., Junghans, A., De Boer, B., Driomina, E. S., Briviba, K. & Sies, H. (1998) Carotenoid mixture protect multimellar liposomes against oxidative damage: synergistic effects of lycopene and lutein. FEBS Lett, 427, 305-308.