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Ultraweak Photon Emission as a Non-Invasive Health Assessment: A Systematic Review

  • John A. Ives ,

    jives@siib.org

    Affiliation Samueli Institute, Alexandria, Virginia, United States of America

  • Eduard P. A. van Wijk,

    Affiliations Netherlands Metabolomics Centre, Division of Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands, Sino-Dutch Centre for Preventive and Personalized Medicine/Centre for Photonics of Living Systems, Leiden University, Leiden, The Netherlands, Meluna Research, Amersfoort, The Netherlands

  • Namuun Bat,

    Affiliation Samueli Institute, Alexandria, Virginia, United States of America

  • Cindy Crawford,

    Affiliation Samueli Institute, Alexandria, Virginia, United States of America

  • Avi Walter,

    Affiliation Samueli Institute, Alexandria, Virginia, United States of America

  • Wayne B. Jonas,

    Affiliation Samueli Institute, Alexandria, Virginia, United States of America

  • Roeland van Wijk,

    Affiliations Sino-Dutch Centre for Preventive and Personalized Medicine/Centre for Photonics of Living Systems, Leiden University, Leiden, The Netherlands, Meluna Research, Amersfoort, The Netherlands

  • Jan van der Greef

    Affiliations Netherlands Metabolomics Centre, Division of Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands, Sino-Dutch Centre for Preventive and Personalized Medicine/Centre for Photonics of Living Systems, Leiden University, Leiden, The Netherlands, Netherlands Organization for Applied Scientific Research, Zeist, The Netherlands

Ultraweak Photon Emission as a Non-Invasive Health Assessment: A Systematic Review

  • John A. Ives, 
  • Eduard P. A. van Wijk, 
  • Namuun Bat, 
  • Cindy Crawford, 
  • Avi Walter, 
  • Wayne B. Jonas, 
  • Roeland van Wijk, 
  • Jan van der Greef
PLOS
x

Abstract

We conducted a systematic review (SR) of the peer reviewed scientific literature on ultraweak photon emissions (UPE) from humans. The question was: Can ultraweak photon emissions from humans be used as a non-invasive health assessment? A systematic search was conducted across eight relevant databases: PubMed/MEDLINE, BIOSIS, CINAHL, PSYCHINFO, All of Cochrane EBM databases, GIDEON, DoD Biomedical Research, and clinicaltrials.gov from database inception to October 2011. Of the 1315 studies captured by the search strategy, 56 met the inclusion criteria, out of which 1 was a RCT, 27 were CCT, and 28 were observational and descriptive studies. There were no systematic reviews/meta-analyses that fit the inclusion criteria. In this report, the authors provide an assessment of the quality of the RCT included; describe the characteristics of all the included studies, the outcomes assessed, and the effectiveness of photon emission as a potential health assessment tool. This report demonstrates that the peer reviewed literature on UPE and human UPE measurement in particular is surprisingly large. Most of the human UPE literature is of good to high quality based on our systematic evaluation. However, an evaluation tool for systematically evaluating this type of “bio-evaluation” methodology is not currently available and would be worth developing. Publications in the peer reviewed literature over the last 50 years demonstrate that the use of “off-the-shelf” technologies and well described methodologies for the detection of human photon emissions are being used on a regular basis in medical and research settings. The overall quality of this literature is good and the use of this approach for determining inflammatory and oxidative states of patients indicate the growing use and value of this approach as both a medical and research tool.

Introduction

Bioluminescence is the process of production and emission of light by a living organism via chemiluminescence-based processes. Many examples are known in biology such as fireflies, Antarctic krill, fungi (for instance Panellus stipticus), various squid species, etc.

In fact, all cells produce some form of light emission, but most of this light is not visible to the unaided human eye. This photonic emission has characteristic wavelengths, duration, timing and patterns of flashes. These are features often associated with information and, while not proof in and of itself, it is reasonable to assume that these light emissions contain and carry information about the biological systems that produced it.

Ultraweak photon emission by living systems, sometimes called low level chemiluminescence, is the result of normal biochemical reactions in which electrons transition in and out of electronically excited states. Detection and identification of these excited states is easily achieved in well-defined chemical systems. However, the task becomes more problematic in complex biological systems, e.g., in studies of isolated cells, organs, or intact organisms.

The advent of new photon counting technologies in the early 1960’s provided the tools to demonstrate the existence of a ubiquitous low level luminescence in organisms. This provided convincing evidence that light from living organisms was not restricted to life forms having special organs containing enzyme systems such as luciferase/luciferin. This early work was primarily done in the USSR [1], [2] with a few exceptions [3]. Russian research was sometimes translated into English [4]. By that time it had been established in inorganic chemical systems that chemiluminescence could occur in oxidative reactions as a consequence of the recombination of oxygen-containing radicals [5], [6] and thus provided information about radical reactions and oxidation mechanisms. Outside the USSR, the existence of this radiation was neglected or considered a phenomenon that could be caused by external interferences of an unknown nature [7]. In the 1970’s, the existence of this photonic emission from living organisms was confirmed by research teams from Australia [8], Poland [9], Japan [10] and the USA [11]. Emissions are in the order of 10-104 photons/s.cm2, and have been demonstrated in bacteria, yeast, whole animals and plants as well as cells and homogenates from organisms.

For yeasts (Saccharomyces cerivisiae and Schizosaccharomyces pombe) it was established that ultraweak photon emission was dependent on oxygenation and that spectral composition differed between the exponential growth and the stationary phase of the culture [8], [12], [13], [14]. Similar studies were later performed on the bacterium Escherischia coli [15], [16]. In mammalian systems UPE was studied at the organ, cellular and subcellular level. Ultraweak photon emission of rat liver was oxygen dependent, and increased by infusion of hydroperoxides. Spectral analysis indicated a predominance of red light-emitting species arising from the singlet oxygen dimole-emission peaks [11], [17]. Similar spectral data as well as oxygen dependency were obtained with isolated hepatocytes. Estimations of biochemical markers of lipid peroxidation combined with counts of photon emission led to the conclusion that UPE monitors the steady state concentration of singlet molecular oxygen [10], [11], [17], [18], [19]. Therefore, ultraweak photon emission can provide a useful tool to examine oxygen-dependent radical damage which affords an advantage over parameters (such as malondialdehyde levels) measuring accumulative effects.

Since the early 1980’s, it has been known that peroxidal lipid reactions are important components in the etiology of diabetes, liver and lung diseases, arteriosclerosis, ageing and cancer [20], [21], [22], [23], [24]. The production of oxygen radicals during the respiratory burst of phagocytic cell activity plays an essential role in bacterial killing and in regulating the processes of acute inflammation [25], [26]. In view of the damaging effects of oxygen radicals on tissues, it follows that anything causing abnormal activation of phagocytes has the potential to provoke a self-destructive response, most strikingly seen in autoimmune diseases [27]. This realization led to the idea that ultraweak photon emission determined in blood might be a general marker for health and could be used for diagnostic and clinical purposes [28], [29]. Early studies established the interdependence between various diseases and UPE intensity by measuring the differences between the luminescence of the blood of healthy and diseased human subjects. UPE of blood from patients with diabetes mellitus, carcinomas and hyperlipidemia showed higher emission levels than those of the samples from healthy people [28].

The development of a diagnostic assay based on ultraweak photon emission remained limited due to difficulties and requirements of ultra-high sensitive photon counting systems in the application to biomedical measurements [10], [28]. The use of chemiluminigenic probes - substances whose oxidation gives a high yield of electronically excited products – solved many of these issues by increasing the photon output by several orders of magnitude. For this purpose luminol at concentration 0.1–10 µM has been employed, for instance in assays of phagocytosis [25], . Lucigenin has also been sporadically used as a chemiluminigenic enhancer [26].

The next great challenge for the field of ultraweak photon emission detection (in relation to oxidative processes) was to provide images of these low signals in addition to physiological information. A two-dimensional photon counting imaging of a rat’s brain was technically achieved in 1999 [33], [34]. The equipment used in this first experiment consisted of a two-dimensional photon counting tube, a highly efficient lens system, and an electronic device to record time series of a photoelectron train with spatial information. Another application of two-dimensional imaging of these photon emissions has been in the field of cancer. In bladder cancer, transplanted into the feet of nude mice, the increase in photon emission in early developing cancer indicates the actively proliferating cancer before any detection of necrosis, haemorrhage, leukocyte infiltration or crusta formation [35]. Cancer imaging in mice transplanted with ovarian cancer cells utilizing a highly sensitive charge-coupled device (CCD) camera system has confirmed the increased UPE of tumours [36].

The major trends over the last 50 years are schematically shown in Figure 1. Since the original observation of the effect, UPE detection methodology has matured to be uniquely positioned for not only providing insight into detailed biochemical processes but also provide a non-invasive tool for observing and even understanding system organisation.

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Figure 1. Major trends in UPE developments in the last 50 years.

The historical development of this field can be subdivided in five main areas: (1) the initiation of research of UPE with photomultiplier tubes in USSR and its connection to radical oxygen species (ROS) and lipid peroxidation, (2) the recognition of UPE world wide and globalization of this research, (3) the use of UPE as a non-invasive diagnostic marker, (4) the extension of time measurement into spatial patterns, and (5) the use of photon count distributions (PCD) and statistics (PCS) (based on fluctuations in the number of photons in successive counting in contiguous measurement times) for detecting a ‘light language’ that is connected with the system’s organization of the living biological state.

https://doi.org/10.1371/journal.pone.0087401.g001

Knowledge of the excitation state of biochemical reactions in organisms and isolated biological systems is of significant value for assessing basic biological function. In the case of whole organisms, a general and often specific assessment of health and wellness is possible with knowledge of the “reactive” or relative excitation state of intrinsic biochemical reactions. Therefore, it is possible, using detection and quantification of ultraweak photon emission, to non-invasively assess a person’s health, specifically the level of stress on biochemical and metabolic systems from the production of reactive oxygen species (ROS) as ROS are the principle source of these photons [5], [6], [22]. The 50 years of progress in this field has, thanks to advances in technologies for measuring ultraweak photon emissions, led to the emerging discipline of ‘human photon emission’.

To date, there have been no reviews of the literature to ascertain if ultraweak photon emission can be effectively used as a non-invasive health assessment tool. The purpose of this systematic review was to: 1) survey the literature on ultraweak photon emissions as they relate to human studies; 2) assess the quantity and quality of the research found; and 3) characterize the results by whether the study had an intervention or not, 4) what research model was studied, and 5) the potential value of using photons as a health assessment tool.

Materials and Methods

Search strategy

A systematic search was conducted across eight relevant databases: PubMed/MEDLINE, BIOSIS, CINAHL, PSYCHINFO, All of Cochrane EBM databases, GIDEON, DoD Biomedical Research, and clinicaltrials.gov from database inception to October 2011. The keywords related to photon were pre-identified by the team with guidance from subject matter experts. The final search terms decided upon and searched across databases were: photon, external bioenergy, spontaneous photon emission, ultraweak photon emission, ultraweak chemiluminescence, low level light emission, spontaneous chemiluminescence, ultraweak photons, ultra-weak photon emission, ultra-weak photons, ultra-weak chemiluminescence. See Appendix S1 for a full detail of the search in PubMed. Variations of this strategy were adapted for each unique database and are available upon request.

The search was limited to English language and human population only where databases allowed for these limitations. There was no limitation to study design in the initial search. Grey literature was searched by accessing and communicating with subject matter experts in the field and sharing their database collections as a cross reference to what the original search strategy retrieved as well as conducting basic internet searching across the keyword scheme. The reviewers also hand-searched bibliographies of all included studies to ensure that a comprehensive search strategy was used.

Selection criteria

All study designs were included, however, for the purpose of the analysis, only the controlled clinical trial (CCT) and randomized control trial (RCT) study designs were considered. Studies were included in the analysis if they were: 1) in human populations, 2) describing the use of photons as a health assessment tool, 3) used in comparison with a placebo control or untreated control for the systematic review assessment, and 4) measuring ultraweak photon emission. Studies were excluded if they were categorized as: thought pieces, descriptive reviews, editorials, and all studies relating primarily to the physics of photons.

Study selection

Three reviewers independently screened the titles and abstracts of all retrieved references according to the inclusion criteria presented above. All studies had to have some discussion concerning intrinsic light from live subjects in order to be considered for inclusion. Full text articles were pulled for all publications where a reviewer felt there was a potential for meeting inclusion criteria. At this point all study designs were included.

Quality assessment and data extraction

The retrieved full-text articles were put into buckets of study designs by RCT, CCT, observational, descriptive, and mixed methods in order to assess the quantity and quality, and describe the characteristics of the individual included studies.

The RCT study design was assessed for quality according to the Scottish Intercollegiate Guidelines Network (SIGN 50) [37], a well-accepted and validated tool for assessing quality used widely in both complementary and alternative medicine (CAM) and conventional literature (see Table 1 for a full description of the SIGN 50 criteria). Because all of the rest of the studies reported here involved photons as an adjunctive assessment of the inflammatory state and not as the primary diagnostic assessment or necessarily including an intervention per se, the authors felt that the full SIGN criteria was not a good fit for evaluating the quality of the photonic portion of these studies. After examining the other quality assessment tools, the authors decided that none fit the photonic literature examined here. Because of this, the CCT study designs were only assessed across one of the criteria addressed in SIGN that fit. The other study designs (observational, descriptive and mixed methods) were only tallied as to how many fit the inclusion criteria laid out above.

A data extraction form was created during the protocol development stage and tested by the team before use. This form captured details on the system of research, the objective of the study, the conditions and descriptions of the study population, the type of control, the specific outcomes and results related to photon emission and the authors’ main conclusions in order to provide a descriptive detail of the characteristics of the included studies.

All five reviewers were trained in the methodology for quality assessment and data extraction by the review manager (C.C.) and a rule book was created to assist in answering the questions objectively and consistently, which ensured reproducibility in the end, which was pilot tested among the team members. Forms were created in an online system offered through the Samueli Institute’s SharePoint cite to allow the reviewers to complete the data extraction. The 5 trained reviewers simultaneously extracted the data independently of each other (two reviewers assigned to each individual article) and all answers were tracked through this system. Any and all conflicts were resolved through discussions in team meetings. Once collected, all data was downloaded into an Excel table for each study and formatted in preparation for inclusion in Tables 24.

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Table 2. Descriptive data for randomized controlled trials that have an intervention.

https://doi.org/10.1371/journal.pone.0087401.t002

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Table 3. Descriptive data for clinical trials that have an intervention.

https://doi.org/10.1371/journal.pone.0087401.t003

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Table 4. Descriptive data for clinical trials that have no intervention.

https://doi.org/10.1371/journal.pone.0087401.t004

All included studies were then characterized as to whether there was an intervention and what system of research they fell into (whole body, cells [blood cells, other cells], fluids [blood plasma, urine, cerebral fluid, saliva], and other [tissue]). These categories were chosen not only because the articles naturally broke into these categories but also they make intrinsic bio-medical sense.

The effect size was not calculated due to the heterogeneity of the trials identified during the review phase. All assessments were based on information provided in the published manuscripts that met the inclusion criteria.

Results

Of the 1315 studies captured by our search strategy, 56 met the inclusion criteria, out of which 1 was a RCT, 27 were CCTs, and 28 were observational and descriptive studies. There were no systematic reviews/meta-analyses that fit our inclusion criteria. See Figure 2 for a graphical depiction of the study selection and elimination process throughout the review phases. In this report, the authors provide an assessment of the quality of the RCT included; describe the characteristics of all the included studies, the outcomes assessed, and the effectiveness of photon emission as a potential health assessment tool. The RCT and CCT study designs are presented descriptively in Tables 24. Other formal study designs included are narratively summarized below and will be reported on in more detail in future publications.

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Figure 2. Flow chart.

There were a total of 1315 records identified through the literature search, out of which 1113 were screened based on abstracts after removal of duplicates. The first level of screening based on abstracts resulted in exclusion of 1048 records (descriptive reviews, editorials, theories, books, book sections, non-human studies, and grey literature that didn’t fit our inclusion criteria), and the second level of screening based on full-text resulted in exclusion of 9 more additional records. Therefore, a total of 56 studies (1 randomized controlled clinical trial, 27 controlled clinical trials, and 28 observational/descriptive studies) were included in this review.

https://doi.org/10.1371/journal.pone.0087401.g002

Quality assessment of RCT

Of the 56 included studies, only one was categorized as a RCT. In this study, the effect of plant adaptogens on human ultraweak photon emission was determined by providing subjects with supplements of Rhodiola rosea, placebo pills, or ADAPT-32 (mix of adaptogens) for one week, and measuring the ultraweak photon emission from the dorsal side of their hands. The results show a significant decrease in photon emission (p = 0.027), as well as in reported fatigue levels (p = 0.049) in the Rhodiola group compared to the placebo group. However, this work would have been better with the groups approximately matched for age. This RCT received an overall quality score of (+) according to the SIGN 50 criteria. The authors did not provide a full description of the randomization process and allocation concealment methodology in the published report. Although they did not address these important components, because of the strength in the other criteria assessed the conclusions of the study are thought unlikely to be altered by the inclusion of this missing information. We also believe there is a low level of bias being introduced to this study. Further studies employing an RCT design are needed to determine the value of photon emission measurement as a tool for assessing the impact of supplement use as well as other interventions meant to improve health. See Table 2 for further details of the study [38].

Controlled clinical trials

Of the 56 included studies, 27 were characterized as CCT study design, out of which 17 studies involved no intervention (Table 4) while the remaining 11 studies had an intervention (Table 3). It is interesting to note that most interventional studies came up in the literature post-2003 with the exception of Hans 1997 [39], whereas all of the research in the last two decades of the 1900’s (1982–2003) involved no intervention. In the Hans study, the effect of total intravenous anesthesia on the plasma antioxidant capacity of neurosurgical patients during a cerebrospinal shunt was studied. It was a first of its kind to measure ultraweak chemiluminescence of patients’ plasma before and after an intervention. All the other research was focused on assessing and comparing the state of inflammation among different groups for future diagnosis purposes. These studies were grouped by their system of research. The most commonly studied system of research was blood cells (9) [40], [41], [42], [43], [44], [45], [46], [47], [48] followed by whole body (8) [49], [50], [51], [52], [53], [54], [55], [56], blood plasma (4) [39], [57], [58], [59], tissues (2) [60], [61], urine (2) [62], [63], saliva (1) [64], and other cells (1) [65].

The inflammatory states studied in the various publications included respiratory inflammations such as anthrax, chronic bronchitis, pneumonia, lung injury, and smoking as well as a number of other conditions such as, ulcerative colitis, multiple sclerosis, cancer, ankylosing spondylitis, hemodialysis, and varicocele. There were three studies [53], [54], [56] that looked at the ultraweak photon emission of experienced meditation practitioners compared to practitioners with no experience. All three studies found decreased photon emission in the experienced meditation groups compared to the control groups.

Observational and descriptive studies

Of the 56 included studies, 28 were characterized as observational and descriptive studies, out of which 20 studies used whole body[56], [66], [67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78], [79], [80], [81], [82], [83], [84], 3 blood cells[85], [86], [87], 3 saliva[64], [88], [89], 1 blood plasma[90], and 1 breath[91] as systems of research. The details of these studies will be reported on in future publications.

Discussion

Main findings

Publications in the peer reviewed literature over the last 50 years clearly demonstrate that the use of “off-the-shelf” technologies and well described methodologies for the detection of human photon emissions are being used on a regular basis in medical and research settings. Our search turned up only one RCT. While of good quality (SIGN score of “+”), clearly this field needs more RCTs to truly test the use of UPEs as a diagnostic tool. The overall quality of this literature is good and the use of this approach in medical oncology settings for determining inflammatory and oxidative states of patients indicate the growing use and value of this approach.

Strength and limitations

Because of this system of research, there is no quality rating tool available in the literature to accurately assess the quality of UPE research. This type of research is neither diagnostic as defined in some of the quality tools for diagnostic studies nor do the studies we found consist of clinical trials with clearly defined intervention and control. SIGN 50 Diagnostic Tool for assessing quality looks at whether the results reflect the accuracy of the diagnostic test being evaluated. This is not what these groups of studies did as they were looking at photons as an adjunctive assessment of the inflammatory state and not as the primary diagnostic assessment, or including an intervention necessarily which made finding a tool to fit these designs of studies very challenging [37]. Other tools were explored and they too did not fit within the scope of the research examined in this review. The limitation of this systematic review is that we are not able to fully comment on the overall quality of these studies captured in this review without this tool in place. Since this research seems promising, it would be worthwhile to determine how best to assess quality of this system of research for future reviews. We were however able to document the quantity of the literature that exists in a rigorous, systematic way in this area and describe the literature as it exists today which is beneficial to understanding how it could be used as a health assessment tool and what has been done to date using this method. Since this research seems promising, it would be worthwhile to determine how best to assess quality of this system of research for future reviews. At this point, provided this limitation, the authors can only say subjectively that the quality is “good” for the CCT study designs evaluated.

Implications for research

Technological advances and improved understanding of the underlying biology have combined to enable the measurement of human photons in a rapid and reliable manner. The technology has advanced sufficiently to allow for non-invasive whole body measurements of these relatively rare photons and there is some evidence that measuring from the hands is sufficient [92]. This has the potential to provide both the researcher and the diagnostician with a powerful tool to look within the body, in real-time, at the fundamental biochemistry and production of ROS and correspondingly the REDOX state of the metabolism [93]. While the production of ROS is an unavoidable by-product of metabolism [94], when it is not properly managed by the body or when it is excessive as under certain kinds of stress [95], [96] it can lead to a number of pathologies.

As ROS have been shown to be associated with a number of disease states it is clearly of use to assess their presence and prevalence. Therefore, assessing ROS levels may be useful for tracking the impact of various interventions, behaviors or medications. Doing so in a non-invasive and easy way is of great import.

Conclusion

Our study demonstrates that the peer reviewed literature around UPE and human UPE measurement in particular is surprisingly large. Most of the human UPE literature is of good to high quality based on our systematic evaluation. However, an evaluation tool for systematically evaluating this type of “bio-evaluation” methodology is not currently available and would be worth developing. The authors applied their experience in performing systematic reviews to perform this evaluation from the available tools.

In addition, the field of human photon detection and the technology for measuring same has matured to the point where RCTs should be performed. In this way, it will be possible to determine if this approach can deliver a tool for non-invasively evaluating the specific inflammatory state of the individual while simultaneously providing a general measure of overall health. Finally, detection of human photon emissions has the potential for broad applicability to human health and disease monitoring at the whole systems level.

Supporting Information

Checklist S1.

PRISMA 2009 Checklist. PRISMA checklist contains the preferred reporting items for Systematic Reviews and Meta-Analyses. The section of this article where each item is addressed is provided here.

https://doi.org/10.1371/journal.pone.0087401.s001

(DOC)

Appendix S1.

Pubmed Search Details. The search terms and limits used in Pubmed, and the dates the search was conducted is provided here.

https://doi.org/10.1371/journal.pone.0087401.s002

(DOCX)

Acknowledgments

The manuscript is a result of the cooperation between Samueli Institute and Sino-Dutch Centre for Preventive and Personalized Medicine, University of Leiden. The authors would like to thank LaDonna Johnson for administrative support.

Author Contributions

Conceived and designed the experiments: JI CC EW NB. Performed the experiments: CC NB AW JI EW. Analyzed the data: CC NB EW JI AW. Contributed reagents/materials/analysis tools: CC. Wrote the paper: JI CC NB EW RW WJ JG.

References

  1. 1. Tarussov BN, Polidova AI, Zhuravlyov AI (1961) Investigation of super low spontaneous luminescence of animal cells. Biofizika (in Russian) 6: 490–492.
  2. 2. Tarussov BN, Polidova AI, Zhuravlyov AI (1961) Discovery of chemiluminescence in mice liver. Radiobiologiya (in Russian) 1: 150–151.
  3. 3. Stauff J, Schmidkunz H (1962) Chemilumineszenz von Oxydationsreaktionen. Z. Phys Chem 33: 274–276.
  4. 4. Vladimirov YA (1966) Ultraweak Luminescence Accompanying Biochemical Reactions (English transl.). Springfield, Vermont: NASA, C.ES.T.I.
  5. 5. Vassil'Ev RF, Vichutinskii AA (1962) Chemiluminescence and Oxidation. Nature 194: 1276–1277.
  6. 6. Stauff J, Schmidkunz H, Hartmann G (1963) Weak chemiluminescence of oxidative reactions. Nature 198: 281–282.
  7. 7. Metcalf WS, Quickenden TI (1967) Mitogenetic radiation. Nature 216: 169–170.
  8. 8. Quickenden TI, Comarmond MJ, Tilbury RN (1985) Ultraweak bioluminescence spectra of stationary phase Saccharomyces cerevisiae and Schizosaccharomyces pombe. Photochem Photobiol 41: 611–615.
  9. 9. Slawinska D, Slawinski J (1983) Biological Chemiluminescence. Photochemistry and Photobiology 37: 709–715.
  10. 10. Inaba H (1988) Super-high sensitivity systems for detection and spectral analysis of ultraweak photon emission from biological cells and tissues. Experientia 44: 550–559.
  11. 11. Boveris A, Cadenas E, Reiter R, Filipkowski M, Nakase Y, et al. (1980) Organ chemiluminescence: noninvasive assay for oxidative radical reactions. Proc Natl Acad Sci U S A 77: 347–351.
  12. 12. Quickenden TI, Que Hee SS (1974) Weak luminescence from the yeast Saccharomyces cerevisiae and the existence of mitogenetic radiation. Biochem biophys Res Commun 60: 764–770.
  13. 13. Quickenden TI, Que Hee SS (1976) The spectral distribution of the luminescence emitted during growth of the yeast Saccharomyces cerevisiae and its relationship to mitogenetic radiation. Photochem Photobiol 23: 201–204.
  14. 14. Quickenden TI, Tilbury RN (1983) Growth dependent luminescence from cultures of normal and respiratory deficient Saccharomyces cerevisiae. Photochem Photobiol 37: 337–344.
  15. 15. Tilbury RN (1992) The effect of stress factors on the spontaneous photon emission from microorganisms. Experientia 48: 1030–1041.
  16. 16. Tilbury RN, Quickenden TI (1988) Spectral and time dependence studies of the ultraweak bioluminescence emitted by the bacterium Escherichia coli. Photochem Photobiol 47: 145–150.
  17. 17. Boveris A, Cadenas E, Chance B (1981) Ultraweak chemiluminescence: a sensitive assay for oxidative radical reactions. Fed Proc 40: 195–198.
  18. 18. Cadenas E (1984) Biological chemiluminescence. Photochem Photobiol 40: 823–830.
  19. 19. Cadenas E, Wefers H, Sies H (1981) Low-level chemiluminescence of isolated hepatocytes. Eur J Biochem 119: 531–536.
  20. 20. Blake DR, Hall ND, Bacon PA, Dieppe PA, Halliwell B, et al. (1981) The importance of iron in rheumatoid disease. Lancet 318: 1142–1144.
  21. 21. Halliwell B, Gutteridge JM (1984) Lipid peroxidation, oxygen radicals, cell damage, and antioxidant therapy. Lancet 323: 1396–1397.
  22. 22. Halliwell B, Gutteridge JM (1985) Free radicals in biology and medicine. Free Radical Biology and Medicine 1: 331–334.
  23. 23. Halliwell B, Gutteridge JM (1986) Oxygen free radicals and iron in relation to biology and medicine: some problems and concepts. Arch Biochem Biophys 246: 501–514.
  24. 24. Halliwell B, Gutteridge JM (1990) Role of free radicals and catalytic metal ions in human disease: an overview. Methods Enzymol 186: 1–85.
  25. 25. Allen RC (1982) Chemiluminescence and the study of phagocyte redox metabolism. Adv Exp Med Biol 141: 411–421.
  26. 26. Allen RC, Mills EL, McNitt TR, Quie PG (1981) Role of myeloperoxidase and bacterial metabolism in chemiluminescence of granulocytes from patients with chronic granulomatous disease. J Infect Dis 144: 344–348.
  27. 27. Halliwell B (1982) Production of superoxide, hydrogen peroxide and hydroxyl radicals by phagocytic cells: a cause of chronic inflammatory disease? Cell Biol Int Rep 6: 529–542.
  28. 28. Inaba H, Yamagishi A, Takyu C, Yoda B, Goto Y, et al. (1982) Development of an ultra-high sensitive photon counting system and its application to biomedical measurements. Optics and Lasers in Engineering 3: 125–130.
  29. 29. Swinbanks D (1986) Japan: body light points to health. Nature 324: 203.
  30. 30. Allen RC, Pruitt BA Jr (1982) Humoral-phagocyte axis of immune defense in burn patients. Chemoluminigenic probing. Arch Surg 117: 133–140.
  31. 31. Horan TD, English D, McPherson TA (1982) Association of neutrophil chemiluminescence with microbicidal activity. Clin Immunol Immunopathol 22: 259–269.
  32. 32. Parnham MJ, Bittner C, Winkelmann J (1981) Macrophages from different sources, their production of chemiluminescence under various stimuli and the effects of PGE2 and drugs. Inflammation Research 11: 617–619.
  33. 33. Kobayashi M (2005) Two-dimensional imaging and spatiotemporal analysis of biophoton. Biophotonics. In: Shen X, Wijk R, editors: Springer US. pp. 155–171.
  34. 34. Kobayashi M, Takeda M, Ito K, Kato H, Inaba H (1999) Two-dimensional photon counting imaging and spatiotemporal characterization of ultraweak photon emission from a rat's brain in vivo. J Neurosci Methods 93: 163–168.
  35. 35. Amano T, Kumini K, Nakashima K, Uchibayashi T, Hisazumi H (1990) A combined therapy of hyperthermia and tumor necrosis factor for nude mice bearing KK-47 bladder cancer. J Urol 144: 370–374.
  36. 36. Takeda M, Kobayashi M, Takayama M, Suzuki S, Ishida T, et al. (2004) Biophoton detection as a novel technique for cancer imaging. Cancer Sci 95: 656–661.
  37. 37. Scottish Intercollegiate Guidelines Network (2008) SIGN 50: A Guideline Developer’s Handbook. Edinburgh: Elliot House. 104 p.
  38. 38. Schutgens FW, Neogi P, van Wijk EP, van Wijk R, Wikman G, et al. (2009) The influence of adaptogens on ultraweak biophoton emission: a pilot-experiment. Phytother Res 23: 1103–1108.
  39. 39. Hans P, Deby-Dupont G, Deby C, Pieron F, Verbesselt R, et al. (1997) Increase in antioxidant capacity of plasma during propofol anesthesia. J Neurosurg Anesthesiol 9: 234–236.
  40. 40. Alexeyev OA, Morozov VG, Suzdaltseva TV, Mishukov AS, Steinberg LA (1994) Impaired neutrophil function in the cutaneous form of anthrax. Infection 22: 281–282.
  41. 41. Hammann KP, Roeder R, Hopf HC (1987) The behaviour of OKT3-, OKT4- and OKT8-positive cells during phases of elevated spontaneous chemiluminescence activity (CL-A) in multiple sclerosis patients. A serial study. Journal of Neurology 234: 25–30.
  42. 42. Ho K-J, Chen P-Q, Chang C-Y, Lu F-J (2000) The oxidative metabolism of circulating phagocytes in ankylosing spondylitis: Determination by whole blood chemiluminescence. Annals of the Rheumatic Diseases 59: 338–341.
  43. 43. Holzer K, Hofmann D, Oppermann E, Zeuzem S, Mönch C, et al. (2010) Neutrophil phenotype and function in partial hepatectomy in man. Langenbeck's Archives of Surgery 395: 643–653.
  44. 44. Koval'chuk L, Gankovskaya L, Borisova A, Golubeva N, Khanukhova L (1998) Effect of cytokines on the generation of active oxygen species by pulmonary and peripheral blood phagocytes. Bulletin of Experimental Biology and Medicine 126: 1035–1037.
  45. 45. Safronova VG, Matveeva NK, Avkhacheva NV, Sidel'nikova VM, Van'ko LV, et al. (2003) Changes in regulation of oxidase activity of peripheral blood granulocytes in women with habitual abortions. Bulletin of Experimental Biology and Medicine 136: 257–260.
  46. 46. Terpigorev SA, Il'chenko VA, Vasilenko IA, Slinchenko OI, Stotskaya TV, et al. (2003) Correlation between the Results of Glucocorticoid Therapy and in Vitro Effect of Glucocorticoids on Monocytes in Asthma. Bulletin of Experimental Biology and Medicine 135: 582–585.
  47. 47. Tsai CH, Pan TL, Lee YS, Tai YK, Liu TZ (2004) Evidence that high-dose L-arginine may be inappropriate for use by diabetic patients as a prophylactic blocker of methylglyoxal glycation. J Biomed Sci 11: 692–696.
  48. 48. Zimmermann B, Dalhoff K, Braun J (1999) Impaired neutrophil exocytosis in patients with severe pneumonia. Intensive Care Medicine 25: 44–51.
  49. 49. Hagens R, Khabiri F, Schreiner V, Wenck H, Wittern KP, et al. (2008) Non-invasive monitoring of oxidative skin stress by ultraweak photon emission measurement. II: biological validation on ultraviolet A-stressed skin. Skin Res Technol 14: 112–120.
  50. 50. Jain A, Rieger I, Rohr M, Schrader A (2010) Antioxidant efficacy on human skin in vivo Investigated by UVA-induced chemiluminescence decay analysis via induced chemiluminescence of human skin. Skin Pharmacology and Physiology 23: 266–272.
  51. 51. Park SH, Kim J, Koo TH (2009) Magneto-acupuncture stimuli effects on ultraweak photon emission from hands of healthy persons. J Acupunct Meridian Stud 2: 40–48.
  52. 52. Raschke T, Koop U, Duesing HJ, Filbry A, Sauermann K, et al. (2004) Topical activity of ascorbic acid: From in vitro optimization to in vivo efficacy. Skin Pharmacology and Physiology 17: 200–206.
  53. 53. Van Wijk EP, Lüdtke R, Van Wijk R (2008) Differential effects of relaxation techniques on ultraweak photon emission. Journal of Alternative & Complementary Medicine 14: 241–250.
  54. 54. Van Wijk EP, Van Wijk R, Bajpai RP (2008) Quantum squeezed state analysis of spontaneous ultra weak light photon emission of practitioners of meditation and control subjects. Indian J Exp Biol 46: 345–352.
  55. 55. Van Wijk EP, Van Wijk R, Bosman S (2010) Using ultra-weak photon emission to determine the effect of oligomeric proanthocyanidins on oxidative stress of human skin. J Photochem Photobiol B 98: 199–206.
  56. 56. Van Wijk EPA, Koch H, Bosman S, Van Wijk R (2006) Anatomic characterization of human ultra-weak photon emission in practitioners of Transcendental Meditation and control subjects. The Journal of Alternative and Complementary Medicine 12: 31–38.
  57. 57. Agatsuma S, Nagoshi T, Kobayashi M, Usa M, Watanabe H, et al. (1992) Hydroxyl radical-induced characteristic chemiluminescent spectra from plasma of hemodialysis patients. Clin Chem 38: 48–55.
  58. 58. Calabrese V, Bella R, Testa D, Spadaro F, Scrofani A, et al. (1998) Increased cerebrospinal fluid and plasma levels of ultraweak chemiluminescence are associated with changes in the thiol pool and lipid-soluble fluorescence in multiple sclerosis: The pathogenic role of oxidative stress. Drugs under Experimental and Clinical Research 24: 125–131.
  59. 59. Yoda B, Goto Y, Sato K, Saeki A, Inaba H (1985) Ultra-weak chemiluminescence of smokers’ blood. Archives of Environmental Health 40: 148–150.
  60. 60. Grasso F, Grillo C, Musumeci F, Triglia A, Rodolico G, et al. (1992) Photon emission from normal and tumor human tissues. Experientia 48: 10–13.
  61. 61. Keshavarzian A, Sedghi S, Kanofsky J, List T, Robinson C, et al. (1992) Excessive production of reactive oxygen metabolites by inflamed colon: analysis by chemiluminescence probe. Gastroenterology 103: 177–185.
  62. 62. Barbieri ER, Hidalgo ME, Venegas A, Smith R, Lissi EA (1999) Varicocele-associated decrease in antioxidant defenses. Journal of Andrology 20: 713–717.
  63. 63. Gisler GC, Diaz J, Duran N (1982) Electronically excited species in the spontaneous chemiluminescence of urine and its uses in the detection of pathological conditions. Physiol Chem Phys 14: 335–342.
  64. 64. Goi N, Takagi K, Hirai Y, Harada H, Kari A, et al. (2007) Effect of psychologic stress on peroxidase and thiocyanate levels in human saliva detected by ultraweak chemiluminescence. Journal of Health Science 53: 161–169.
  65. 65. Clark CJ, Pollock AJ, Reid WH, Campbell D, Gemmell C (1988) Role of pulmonary alveolar macrophage activation in acute lung injury after burns and smoke inhalation. Lancet 332: 872–874.
  66. 66. Bajpai RP, Drexel M (2008) Effect of colorpuncture on spontaneous photon emission in a subject suffering from multiple sclerosis. J Acupunct Meridian Stud 1: 114–120.
  67. 67. Benschoten MMV (1992) Measurement of acupoint biophoton emissions via Omura’s bidigital O-ring test with case studies. American Journal of Acupuncture 20: 257–265.
  68. 68. Cohen S, Popp FA (2003) Biophoton emission of human body. Indian Journal of Experimental Biology 41: 440–445.
  69. 69. Hossu M, Rupert R (2006) Quantum events of biophoton emission associated with complementary and alternative medicine therapies: a descriptive pilot study. Journal of Alternative & Complementary Medicine 12: 119–124.
  70. 70. Jung H-H, Woo W-M, Yang J-M, Choi C, Lee J, et al. (2003) Left-right asymmetry of biophoton emission from hemiparesis patients. Indian Journal of Experimental Biology 41: 452–456.
  71. 71. Jung H-H, Woo W-M, Yang J-M, Choi C, Lee J, et al. (2003) Photon counting statistics analysis of biophotons from hands. Indian Journal of Experimental Biology 41: 446–451.
  72. 72. Jung H-H, Yang J-M, Woo W-M, Choi C, Yang J-S, et al. (2005) Year-long biophoton measurements: normalized frequency count analysis and seasonal dependency. Journal of Photochemistry and Photobiology B Biology 78: 149–154.
  73. 73. Kim Tae J, Nam Kyung W, Shin H-S, Lee Sung M, Yang Jong S, et al. (2002) Biophoton emission from fingernails and fingerprints of living human subjects. Acupuncture and Electro-Therapeutics Research 27: 85–94.
  74. 74. Kobayashi M, Kikuchi D, Okamura H (2009) Imaging of Ultraweak Spontaneous Photon Emission from Human Body Displaying Diurnal Rhythm. PLoS One 4: : Article No: e6256.
  75. 75. Laager F, Park S-H, Yang J-M, Song W, Soh K-S (2008) Effects of exercises on biophoton emission of the wrist. European Journal of Applied Physiology 102: 463–469.
  76. 76. TNO Quality of Life (2007) Exploration of Early Diagnosis of Diabetes Mellitus Type 2 Based on Traditional Chinese Medicine by MERID Diagnostics, Biophoton Measurements, Heart Rate Variability and Systems Biology. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 - [cited 2011 Oct]. Available from: http://clinicaltrials.gov/ct2/show/NCT00469287 NLM Identifier: NCT00469287.
  77. 77. Nakamura K, Hiramatsu M (2005) Ultra-weak photon emission from human hand: influence of temperature and oxygen concentration on emission. J Photochem Photobiol B 80: 156–160.
  78. 78. Rastogi A, Pospisil P (2010) Ultra-weak photon emission as a non-invasive tool for monitoring of oxidative processes in the epidermal cells of human skin: comparative study on the dorsal and the palm side of the hand. Skin Res Technol 16: 365–370.
  79. 79. Van Wijk EP, Ackerman J, Van Wijk R (2005) Effect of meditation on ultraweak photon emission from hands and forehead. Forsch Komplementarmed Klass Naturheilkd 12: 107–112.
  80. 80. Van Wijk R, Ackerman JM, Van Wijk EP (2005) Color filters and human photon emission: implications for auriculomedicine. Explore (NY) 1: 102–108.
  81. 81. Van Wijk R, Ackerman JM, van Wijk EPA (2006) Effects of a color filter used in auriculomedicine on ultraweak photon emission of the human body. Journal of Alternative & Complementary Medicine 12: 955–962.
  82. 82. Van Wijk R, Van Wijk EPA, Bajpai RP (2006) Photocount distribution of photons emitted from three sites of a human body. Journal of Photochemistry and Photobiology B Biology 84: 46–55.
  83. 83. Wijk EP, Wijk RV (2005) Multi-site recording and spectral analysis of spontaneous photon emission from human body. Forsch Komplementarmed Klass Naturheilkd 12: 96–106.
  84. 84. Yang JM, Choi C, Hyun h, Woo WM, Yi SH, et al. (2004) Left-right and Yin-Yang balance of biophoton emission from hands. Acupunct Electrother Res 29: 197–211.
  85. 85. Marton IJ, Kiss C (1992) Influence of surgical treatment of periapical lesions on serum and blood levels of inflammatory mediators. Int Endod J 25: 229–233.
  86. 86. Mayer M, Urbanek K (1992) Luminol-dependent chemiluminescence and the clinical course of multiple sclerosis. Acta Univ Palacki Olomuc Fac Med 134: 97–99.
  87. 87. Safronova VG, Matveeva NK, Mal'tseva VN, Bondar OE, Avkhacheva NV, et al. (2006) Generation of reactive oxygen species by umbilical blood cells and immune status of newborns at risk of infectious inflammatory diseases. Bull Exp Biol Med 142: 333–337.
  88. 88. Takagi K, Hasunuma T, Goi N, Harada H, Ikari A, et al. (2005) Short Communication: The effects of performance anxiety on salivary ultra-weak chemiluminescence. Stress & Health 21: 263–268.
  89. 89. Tsuboi H, Hamer M, Tanaka G, Takagi K, Kinae N, et al. (2008) Responses of ultra-weak chemiluminescence and secretory IgA in saliva to the induction of angry and depressive moods. Brain Behav Immun 22: 209–214.
  90. 90. Park YK, Park E, Kim JS, Kang MH (2003) Daily grape juice consumption reduces oxidative DNA damage and plasma free radical levels in healthy Koreans. Mutat Res 529: 77–86.
  91. 91. Williams MD, Chance B (1983) Spontaneous chemiluminescence of human breath. Spectrum, lifetime, temporal distribution, and correlation with peroxide. J Biol Chem 258: 3628–3631.
  92. 92. Van Wijk R, Kobayashi M, Van Wijk EP (2006) Spatial characterization of human ultra-weak photon emission. Journal of Photochemistry and Photobiology B: Biology 83: 69–76.
  93. 93. Van Wijk R, Van Wijk EP, Wiegant FA, Ives J (2008) Free Radicals and Low-level Photon Emission in Human Pathogenesis: State of the Art. Indian J Exp Biol 46: 273–309.
  94. 94. Sies H (1985) Oxidative Stress. New York: Academic Press. 507 p.
  95. 95. Dormandy TL (1989) Free-radical pathology and medicine. A review. J R Coll Physicians Lond 23: 221–227.
  96. 96. Halliwell B (1991) Reactive oxygen species in living systems: source, biochemistry, and role in human disease. Am J Med 91: 14S–22S.