1. Evaluation of the Pharmanex BioPhotonic Scanner<br />Steven Lindner D.C.<br />New York Chiropractic College<br />NTR 5502: Nutritional Assessment<br />Dr. Corey Schuler<br />Winter 2011<br />INTRODUCTION<br />Several studies link oxidative stress to the pathogenesis of many human diseases (Larocca, 2007). Naturally a desire to combat the aversive effects of oxidative stress has emerged and been implemented through the use of antioxidants. Carotenoids, which are a form of antioxidants, have been particularly useful as a measurement of antioxidant intake which is directly related to fruit and vegetable consumption. High performance liquid chromatography (HPLC) has been the accepted gold standard for the assessment of carotenoid levels in blood serum and tissue. However, HPLC involves invasive blood sampling, is impractical for use outside of a clinical setting, time consuming, and expensive. Recently, the use of Ramen spectroscopy has been presented as a rapid, feasible method for noninvasive measurement of carotenoid levels in human skin (Mayne ST, 2010). Pharmanex’s BioPhotonic Scanner employs Ramen Spectroscopy in a quick 90 second scan of the palm to gauge carotenoid levels at the stratum corneum. By using optical signals referred to as Ramen signals, the unique molecular structure of carotenoids is detected, allowing for their measurement without interference from molecules such as melanin. Since carotenoids are reflective of overall antioxidant health in the body, the carotenoid score obtained by the BioPhotonic Scanner enables physicians to acquire a baseline biomarker of their patients antioxidant defense network, objectively recommend a nutritional program for deficient patients, and monitor their patients progress (Cady, 2006). <br />Key Words:<br />Oxidative stress, antioxidants, carotenoids, high performance liquid chromatography, stratum corneum, Ramen signals, biomarker<br />DISCUSSION<br /> Purpose of the Tool<br />Invented by Dr. Werner Gellermann, the BioPhotonic Scanner employs Ramen spectroscopy to determine the amount of carotenoids present in tissue as a measure of overall antioxidant status and well being. With evidence linking carotenoids to health benefits ranging from reduced risk of cataracts to reduced risk of prostate cancer, the scanner becomes a feasible method for patients to monitor carotenoid levels and modify one’s lifestyle to improve their carotenoid score. Parker College President Fabrizio Mancini aptly notes, “This scanner will help all chiropractors maintain a better relationship with their patients through a monthly counseling on how fast their body is aging” (American Chiropractor, July 2007).<br />Explanation to Patients<br />At the most basic level of an organism’s hierarchy of organization is the atom-which itself is comprised of a nucleus and electron shells. When a stable atom loses an electron, oxidative stress occurs resulting in an unstable molecule or free radical. Atoms prefer stability and will seek out electrons from other atoms creating a chain reaction of free radicals. When the number of free radicals increases beyond the body’s ability to neutralize or destroy them, a slew of problems emerge such as altered permeability of cell membranes and damage to DNA. Oxidative stress negatively influences the ageing process, as well as disease, and is generated by numerous factors such as sun exposure, smoking, and pollution. Carotenoids which are a form of antioxidants work to counter combat free radicals, protecting the body at the cellular level (Mortensen et al.,2001; Paiva and Russell, 1999). Five carotenoids in particular, b-carotene, a-carotene, lycopene, lutein, and zeazanthin, are found in the blood and known to be important to our health (Khachik et al., 1992; Gerster, 1993). Based on a study conducted at the Pharmanex Research Institute, individuals with high oxidative stress tend to have low skin carotenoid levels as measeured by Ramen spectroscopy (Smidt and Shieh, 2003). According to Mark Bartlett, Ph.D., “Increasing the antioxidant level in one’s body may be one of the most important keys to anti--aging and longevity” (American Chiropractor, July 2007). <br />The Pharmanex BioPhotonic Scanner non-invasively measures the carotenoid level in the skin of one’s palm using a safe blue light and Ramen Spectroscopy. Why the palm? The thickness of the palm’s stratum corneum, roughly 400 micrometers, makes it an ideal site for scanning. As a result, the laser penetration depth in this layer, which is highly scattering, confines the measurement to the stratum corneum, decreasing variability in scoring. Additionally, differences in pigmentation are minimal in the palm, decreasing interference by melanin. Furthermore, the palm has a high lipid to protein ratio that serves as a barrier against the harmful effects of environmental pollutants. Since carotenoids are lipophillic, carotenoid concentrations are highest in this region. <br />History/Development of the Tool<br />The development of the BioPhotonic Scanner was a direct effect of its purpose. In order to provide physicians with a tool that was sufficient in supplying a service for their patients, developers had to keep efficiency in mind. Since the scanner was one of the first of its kind, there would be a lot of trial and error until the perfect product was invented. There had been other tests that were available for determining one’s antioxidant levels, but none that were reasonably priced and also convenient. This 90 second, twenty dollar scan was developed to fit the needs of the physicians and their patients.<br />The origin of the scanner was based on the effectiveness of the natural chemical compounds themselves, not only the drug counterpart that usually came with side effects. Pharmanex was founded in 1994, but it was not responsible for the first prototype. The scanner was funded and developed by the National Institute of Health and the University of Utah so there was no bias when it came to detecting the efficiency of Pharmanex brand vitamins. Its purpose was to detect Macular Degeneration risk factors. It took sometime between six and eight years for the six foot long laser to be invented that could measure antioxidant levels in the back of the retina. Throughout the inventive process, researchers from the University of Utah discovered that antioxidant levels could also be detected through skin samples.<br />This is when Pharmanex came into the picture. A company representative received a call from the researchers at Utah and was scanned. His results produced the highest recorded antioxidant scores because of the vitamin life-pack that he was taking. He then saw first hand how the scanner could prove the effectiveness of taking vitamins, so Pharmanex began to buy the marketing rights of the scanner from the University of Utah. $100 million was invested into different prototypes in a search for a perfected, functional product.<br />Plausible/Purported Mechanism<br />The scanner functions on the principle of reflected and scattered light discovered by C.V. Raman in 1930, which has since been adapted for the assessment of carotenoids in living tissues (Gellermann et al. in 2000). Raman Spectroscopy is founded on the notion that each species of molecules in the body can reflect a different set of colors when stimulated with a light source of a known frequency. This color spectrum becomes a unique optical fingerprint for particular molecule species. The scanner houses three LEDs; two of which are used for the skin carotenoid measurement and one for internal calibration. The two that perform the measurement are tuned to 471.3 nm and 473.0 nm. When these two frequencies of blue light strike a carotenoid molecule in the palm of the hand, the carotenoids reflect back green light at 507.8 nm and 509.8 nm, which is detected by PMTs. A computer then converts these two reflected frequencies into two peaks and each peak is used in the quantification of the tissue carotenoid levels to generate the Skin Carotenoid Score (Pharmanex product information). <br />Safety of Use<br />Blood concentrations of carotenoids are considered the best biological markers of fruit and vegetable intake, but require blood samples and high performance liquid chromatography (HPLC) which is impractical outside of a clinical setting, expensive and time consuming. However, skin concentrations of carotenoids have been shown to be strongly correlated with plasma concentrations of the same carotenoids. For less than two minutes, Pharmanex’s BioPhotonic Scanner offers a rapid, noninvasive method for measuring the levels of carotenoids in the stratum corneum of the skin through blue green laser excitation well within laser exposure standards. <br />Appropriate Patient Selection Criteria<br /> The Pharmanex BioPhotonic Scanner is suitable for anyone interested in improving their nutritional intake and monitoring their overall antioxidant status to reap the health benefits associated with a diet rich in fruits and vegetables. Additionally, the detection of carotenoid levels can provide diagnostic information which in turn allows the possibility for preventative intervention (Cady, 2006). Similarly, carotenoid scores enable patients who have been placed on a nutritional program to monitor their progress and lower their risk of degenerative diseases that are associated with oxidative stress. For example, several studies support the role of carotenoids-specifically lutein and zeaxanthin- in the prevention of age related eye disease such as a reduced risk of cataracts (Brown et al., 1999; Chasan-Taber et al., 1999) and a reduced risk of macular degeneration (Seddon, 1994; Bone, 2000, 2003; Landrum, 1996, 1997; Elless, 2000; Berstein, 2002). The carotenoid lutein has also been shown to decrease mortality from cardiovascular disease (Kouris-Blazos, 2002) and a slowed progression of pre-atheroscleotic symptoms (Dwyer, 2001). In multiple studies, lycopene has been shown to reduce the risk of myocardial infarction (Kohlmeier, 1997), reduced LDL oxidation (Agarwal, 1998), and reduced LDL cholesterol production (Fuhrman et al., 1997). <br />Case Studies, Testimonials, and Methods of Marketing the Tool.<br />Any medical invention is only as profound as its proof of success or the service that it can provide professionals and their patients. Without reassurance that an invention is legitimate, professionals will be hesitant to use it in their practice. Case studies have been performed in order to validate the Pharmanex Biophotonic Scanner. Researchers studied the reasons why the scanner was successful as to provide reassurance. One case study done by Pharmanex discusses the science behind the Raman signal that is emitted by the laser on the retina. The signal detects the long carbon chain “fingerprint” that is characteristic of carotenoids which in turn have been proven to be reflective of levels of antioxidants in one’s system. Using this mode of detection, researchers began to compare the retina scanner with other health screening tests that focus on numerous other organs. This is what sparked the idea of scanning the largest organ in the body, the skin, in order for the test to be non-invasive, convenient, and successful.<br />Testimonials also support the validity of the Scanner. There is a large collection of peer reviewed medical literature which supported the application for a patent and many other papers that support its truth that were written after a patent was awarded. One of the first scientists that researched carotenoids and the importance of antioxidants themselves was Khachick; “Carotenoids began to be clearly identified in 1992. Khachik and colleagues noted that five were abundant in the human diet, and that among these, five carotenoids – beta carotene, alpha carotene, lycopene, lutein, and zexanthin – are found in the blood and known to be important in human health.” (Khachik, F., 1998). This study, along with many others, proved that carotenoids and antioxidants are truly essential in fighting free radicals. The next step was to show a relationship between levels of carotenoids from tests via skin samples and levels from blood samples. Another study went on to prove this point; “...the levels of seven carotenoids, two retinoids, and two tocopherols were measured in both plasma and well as buccal mucosal cells as well as skin samples from 96 healthy subjects. The data clearly showed a correlation between the levels of micronutrients in plasma as well as skin. Their conclusion was that the status of these micronutrients in the skin may be estimated from their plasma concentrations. The reverse, of course, also holds true...” (El-Sohemy, 2002). The Following step was to prove the anti-cancer effects that carotenoids have. “Carotenoids function as potent antioxidants, and this is clearly a major mechanism of their action. In addition, carotenoids action involves interference in several pathways related to cancer cell proliferation...” (Sharon, Y., 2003).<br />These testimonials, along with countless others, were a key process in marketing the product. Proving the science behind antioxidants, the need of the scanner, the legitimacy of the scanner, and the success of the testimonials are important factors that are used when it was marketed to different companies and physicians. Additionally, Pharmanex guarantees an increased carotenoid score with the use of their LifePak supplementation. The appeal for physicians and patients is two-fold. Physicians are able to stand behind the product with absolute certainty of its function and patients are able to quickly boost their carotenoid score and make it more manageable to maintain it. With a cultural desire to maintain youthful vitality, and with at least eight peer-reviewed studies by third parties unrelated to Pharmanex or the supplementation industry, the BioPhotonic Scanner is a valid method for carotenoid assessment and monitoring its increase (Bernstein, 1998, 2002; Ermakov, 2004a, 2004b; Gellerman, 2002, 2004; Hata 2000; Zhao, 2003). <br />Synopsis of Peer Reviewed Literature<br />After approval of Case Studies and Testimonials, the key factor that makes any project completely valid is Peer Reviewed Literature. Experts in the detecting and the effects of Carotenoids reviewed the Pharmanex Biophotonic Scanner to prove or disprove its legitimacy. Experts from Yale University Schools of Public Health and Medicine in New Haven, Connecticut performed a study to evaluate the “reproducibility and validity of the Resonance Raman Spectroscopy measures of dermal total carotenoids and lycopene in humans”. In the first part of the study 74 men and women with different types on skin pigmentation were scanned. Measures were taken of their palms, inner arms, and outer arms, at different times of the year to maximize seasonal variation. The scanner used light at 488 nm to detect carotenoids and light at 514 nm to detect lycopene. In the second part of the study 28 subjects dietary carotenoid intake was recorded and blood samples were taken to match to carotenoid levels taken from the skin. The results show that levels taken from the skin and from biopsies were significantly correlated with a p-value of 0.0001. Lycopene values were also correlated with a p-value less than 0.0001. In conclusion, tests done by experts of antioxidants not associated with Pharmanex agree that the “Raman Spectroscopy is a feasible and valid method for nonivasively assessing dermal carotenoids as a biomarker for studies of nutrition and health” (Mayne ST et al., 2010) <br />CONCLUSION<br />Overall, the use of Ramen Spectroscopy for the noninvasive assessment of skin carotenoids is not only an accurate reflection of antioxidant health and oxidative stress, but a convenient tool to help patients make healthy adjustments to their lifestyle. With literature supporting the legitimacy of the BioPhotonic Scanner and studies linking antioxidant levels to the prevention of skin cancer, prostate cancer, atherosclerosis, macular degeneration, cataracts, and other degenerative diseases associated with oxidative stress, the scanner is well on its way to becoming a staple in routine check-ups. It may even replace high performance liquid chromatography as the gold standard for carotenoid measurement. Aside from being practical, the BioPhotonic Scanner is cost effective. Pharmanex is a division of Nu Skin Enterprises (Nu Skin purchased them in 1998 for $139M) and Nu Skin uses network marketing as a mode of distribution of its products. While the scanner is not available for purchase, an attractive lease program is available for physicians: <br />1) Sell $4500.00 of company’s products over 1 to 4 months, cumulative. Note that $4500.00 includes monthly re-orders as well, not just brand new sales. All products can be shipped directly to patients so physicians do not need to carry any inventory if they’d prefer not to.<br />2) Purchase a $2750.00 Health Care Professional Package. This allows physicians to apply for the scanner lease immediately. All unopened products come with a 1 year 100% money back guarantee minus 10% for restocking. (Customers get a 30 day unconditional money back guarantee on all products and 60 days money back guarantee on LifePak products if their scanner score does not improve in that timeframe).<br />Healthcare Package<br />9 LifePak Nano<br />3 g3 Juice Bottle 2pk<br />2 LifePak<br />2 Vitox 120ct<br />30 Scan Cards 20pk<br />$300 Product Credit<br />10 Scan Cert Portfolios 10pk<br />5 Product Catalogs <br /> The basic terms of the lease are as follows: 3 years (can be broken at any time), $500 deposit and $209.00 per month. When $3000-$5000 in monthly sales (this included re-orders) is reached, the lease is reduced by 50% and when $5000 is reached, the lease is waived. If one believes in the value of the scanner score then you will want to provide products to your patients that can actually improve that score. Pharmanex products are not the only ones that will generate positive results as exemplified by raw vegans who score incredibly high, but Pharmanex are the only ones that give a 60 day money back guarantee based on performance. Likewise, the cost of a brief 90 second scan for a patient is merely $20 and provides a method to make lifestyle changes that will benefit them for years to come. <br />REFERENCES <br />1. Mayne, ST. Cartmel, B. Scarmo, S. (2010) Noninvasive assessment of dermal carotenoids as a biomarker of fruit and vegetable intake. The American Journal of Clinical Nutrition. 92(4):794-800.<br />2. Agarwal, S. and Rao, A.V. (1998) Tomato lycopene and low density lipoprotein oxidation: A human dietary intervention study. Lipids 33, 981-984<br />3. Bernstein P.S., Raman detection of macular carotenoid pigments in intact human retina. Invest Ophthalmol Vis Sci. 1998 Oct;39(11):2003-11.<br />4. Bernstein ,P.S., Gellermann W. Measurement of carotenoids in the living primate eye using resonance Raman spectroscopy. Methods Mol Biol. 2002;196:321-9.<br />5. Bernstein, P.S., Zhao, D.Y., Resonance Raman measurement of macular carotenoids in normal subjects and in age-related macular degeneration patients. Ophthalmology 2002 Oct;109(10):1780-7.<br />6. Fuhrman, B., Elis, A. and Aviram, M. (1997) Hypocholesterolemic effect of lycopene and beta-carotene is related to suppression of cholesterol synthesis and augmentation of LDL receptor activity in macrophages. Biochemical and Biophysical Research Communications 233, 658-662.<br />7. Khachik, F. et al. Separation and quantification of carotenoids in human plasma. Methods Enzymol. 1992;213:205-19.<br />8. El-Sohemy A, et al. Individual carotenoid concentrations in adipose tissue and plasma as biomarkers of dietary intake. American Journal of Clinical Nutrition. 2002 Jul;76(1):172-9.<br />9. Sharon Y et al. Modulation of transcriptional activity by antioxidant carotenoids. Mol Aspects Med . 2003 Dec;24(6):371-84.<br />10. Bone, R.A., Landrum, J.T., Dixon, Z., Chen, Y. and Llerena,C.M. (2000) Lutein and zeaxanthin in the eyes, serum and diet of human subjects. Experimental Eye Research 71, 239-245.<br />11. Brown, L., Rimm, E.B., Seddon, J.M., Giovanucci, E.L., Chasan-Taber, L., Spiegelman, D., Willett, W.C. and Hankinson, S.E. (1999) A prospective study of carotenoid intake and risk of cataract extraction in US men. American Journal of Clinical Nutrition 70, 517-524.<br />12. Chasan-Taber, L., Willett, W.C., Seddon, J.M., Stampfer, M.J., Rosner, B., Colditz, G.A., Speizer, F.E. and Hankinson, S.E. (1999) A prospective study of carotenoid and vitamin A intakes and risk of cataract extraction in US women [see comments]. American Journal of Clinical Nutrition 70, 509-516.<br />13. Elless, M.P., Blaylock, M.J., Huang, J.W. and Gussman, C.D. (2000) Plants as a natural source of concentrated mineral nutritional supplements. Food Chemistry 71, 181-188.<br />14. Dwyer, J.H., Navab, M., Dwyer, K.M., Hassan, K., Sun, P., Shircore, A., Hama-Lavy, S., Hough, G., Wang, X., Drake, T., Merz, C.N. and Fogelman, A.M. (2001) Oxygenated carotenoid lutein and progression of early atherosclerosis: the Los Angeles atherosclerosis study. Circulation 103, 2922-2927.<br />15. Zhao, D.Y. et al, Resonance Raman measurement of macular carotenoids in retinal, choroidal, and macular dystrophies. Arch Ophthalmol. 2003 Jul;121(7):967-72.<br />16. Hata, T.R., Scholz, T.A., Ermakov, I.V., McClane, R.W., Khachik, F., Gellermann, W. and Pershing, L.K., Non-invasive raman spectroscopic detection of carotenoids in human skin. Journal of Investigative Dermatology. 2000 Sep; 115, 441-448.<br />17. Ermakov I.V. et al. Macular pigment Raman detector for clinical applications. J Biomed Opt. 2004 Jan Feb;9(1):139-48.<br />18. Ermakov I.V.,Ermakova M.R.,McClane R.W. and Gellermann W. Resonance Raman detection of carotenoid antioxidants in living human tissues. Optics Letters 2001;26:1179-81.<br />19. Ermakov, I.V. et al. Noninvasive selective detection of lycopene and beta-carotene in human skin using Raman spectroscopy. J Biomed Opt. 2004 Mar;9(2):332-8.<br />20. Gerster H. Anticarcinogenic effect of common carotenoids. Int J Vitam Nutr Res 1993;63:93-121.<br />21. Gellermann, W., Bernstein PS. Noninvasive detection of macular pigments in the human eye. J Biomed Opt. 2004 Jan-Feb;9(1):75-85.<br />22. Gellermann W. et al, In vivo resonant Raman measurement of macular carotenoid pigments in the young and the aging human retina. J Opt Soc Am A Opt Image Sci Vis. 2002 Jun;19(6):1172-86.<br />23. Kouris-Blazos, A. (2002) Morbidity mortality paradox of 1st generation Greek Australians. Asia Pacific Journal of Clinical Nutrition 11 Suppl 3, S569-S575.<br />24. Larocca, F. (July 2007). Could new scanner redefine wellness care? The American Chiropractor<br />25. Landrum, J.T., Bone, R.A., Joa, H., Kilburn, M.D., Moore, L.L. and Sprague, K.E.. (1997) A one year<br />study of the macular pigment: The effect of 140 days of a lutein supplement. Experimental Eye Research<br />65, 57-62.<br />26. Landrum, J.T., Bone, R.A., Kilburn, M.D., Joa, H. and Gomez, C (1996) Dietary lutein supplementation<br />increases macular pigment (MP). Faseb Journal 10:A242 <br />27. Mortensen A., Skibsted L.H. and Truscott T.G. The interaction of dietary carotenoids with radical species. Arch Biochem Biophys 2001;385:13-9.<br />28. Paiva S.A. and Russell R.M. Beta-carotene and other carotenoids as antioxidants. J Am Coll Nutr 1999;18:426-33.<br />29. Smidt, C.R., Burke, D.S. Nutritional Significance and Measurement of Carotenoids. Current Topics in Nutraceut. Res. 2(2):79-91, 2004.<br />30. Smidt CR, Clinical Screening Study: Use of the Pharmanex BioPhotonic Scanner to assess skin carotenoids as a marker of antioxidant status. Pharmanex Internal Study Report, 2003.<br />31. Smidt,CR, Gellermann WR and Zidichouski JA; Non-invasive Raman spectroscopy measurement of human carotenoid status; FASEB J. 2004 18(4): A480.<br />32. Smidt CR, Effect of LifePak® Supplementation on Antioxidant Status Using BioPhotonic Raman Spectroscopy. Pharmanex in-house Study. 2002.<br />33. Smidt C.R. and Shieh D. Non-invasive biophotonic assessment of skin careotenoids as a biomarker of human antioxidant status. FASEB J 2003; submitted<br />34. Kohlmeier, L., Kark, J.D., Gomez-Gracia, E., Martin, B.C., Steck, S.E., Kardinaal, A.F., Ringstad, J., Masaev, V., Riemersma, R., Martin-Moreno, J.M., Huttunen, J.K. and Kok, F.J. (1997) Lycopene and myocardial infarction risk in the EURAMIC Study. American Journal of Epidemiology 146, 618-626.<br />35. Seddon, J.M., Ajani, U.A., Sperduto, R.D., Hiller, R., Blair, N., Burton, T.C., Farber, M.D., Gragoudas, E.S., Haller, J., Miller, D.T. Yannuzi, L.A. and Willett, W. (1994) Dietary carotenoids, vitamins A, C, and E, and advanced age- related macular degeneration. Eye Disease Case-Control Study Group. Journal of the American Medical Association 272, 1413-1420.<br />36. Cady, L. (2006). The Validity of the Pharmanex BioPhotonic Scanner and a Review of the Literature<br />37. PharmanexMD Conference call: Health Care Professional Overview Call from 10/15/2009<br />