Skin impedance might be a rough measure of Vitamin D – Dec 2021

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A Novel Biosensor and Algorithm to Predict Vitamin D Status by Measuring Skin Impedance

Sensors 2021, 21(23), 8118; https://doi.org/10.3390/s21238118 by Jin-Chul Heo 1,Doyoon Kim 2,Hyunsoo An 2ORCID,Chang-Sik Son 3ORCID,Sangwoo Cho 4 andJong-Ha Lee 1,*ORCID
1 Department of Biomedical Engineering, School of Medicine, Keimyung University, Daegu 42601, Korea
2 Samsung Research, Samsung Electronics, Suwon 16677, Korea
3 Division of Intelligent Robot, Daegu Gyeongbuk Institute of Science and Technology, Daegu 42988, Korea
4 The Center for Advanced Technology in Testing Human Factors, Keimyung University, Daegu 42601, Korea

The deficiency and excess of Vitamin D cause various diseases, necessitating continuous management; but it is not easy to accurately measure the serum vitamin D level in the body using a non-invasive method. The aim of this study is to investigate the correlation between vitamin D levels, body information obtained by an InBody scan, and blood parameters obtained during health checkups, to determine the optimum frequency of vitamin D quantification in the skin and to propose a vitamin D measurement method based on impedance. We assessed body composition, arm impedance, and blood vitamin D concentrations to determine the correlation between each element using multiple machine learning analyses and an algorithm which predicted the concentration of vitamin D in the body using the impedance value developed. Body fat percentage obtained from the InBody device and blood parameters albumin and lactate dehydrogenase correlated with vitamin D level. An impedance measurement frequency of 21.1 Hz was reflected in the blood vitamin D concentration at optimum levels, and a confidence level of about 75% for vitamin D in the body was confirmed. These data demonstrate that the concentration of vitamin D in the body can be predicted using impedance measurement values. This method can be used for predicting and monitoring vitamin D-related diseases and may be incorporated in wearable health measurement devices.
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References

1. 1. Sahay, M.; Sahay, R. Rickets-vitamin D deficiency and dependency. Indian J. Endocrinol. Metab. 2012, 16, 164-176.
2. Cipriani, C.; Pepe, J.; Piemonte, S.; Colangelo, L.; Cilli, M.; Minisola, S. Vitamin D and Its Relationship with Obesity and Muscle. Int. J. Endocrinol. 2014, 2014, 841248.
3. Wang, H.; Chen, W.; Li, D.; Yin, X.; Zhang, X.; Olsen, N.; Zheng, S.G. Vitamin D and Chronic Diseases. Aging Dis. 2017, 8, 346353.
4. Marcinowska-Suchowierska, E.; Kupisz-Urbanska, M.; Eukaszkiewicz, J.; Pludowski, P.; Jones, G. Vitamin D Toxicity-A Clinical Perspective. Front. Endocrinol. 2018, 9, 550.
5. Holm, I.A.; Econs, M.J.; Carpenter, T.O. Chapter 26-Familial Hypophosphatemia and Related Disorders. In Pediatric Bone, 2nd ed.; Glorieux, F.H., Pettifor, J.M., Juppner, H., Eds.; Academic Press: San Diego, CA, USA, 2012; pp. 699-726.
6. Kennel, K.A.; Drake, M.T.; Hurley, D.L. Vitamin D deficiency in adults: When to test and how to treat. Mayo Clin. Proc. 2010, 85, 752-757.
7. Arneson, W.L.; Arneson, D.L. Current Methods for Routine Clinical Laboratory Testing of Vitamin D Levels. Lab. Med. 2013, 44, e38-e42.
8. Stokes, C.S.; Lammert, F.; Volmer, D.A. Analytical Methods for Quantification of Vitamin D and Implications for Research and Clinical Practice. Anticancer. Res. 2018, 38, 1137-1144.
9. Shah, I.; Mansour, M.; Jobe, S.; Salih, E.; Naughton, D.; Salman Ashraf, S. A Non-Invasive Hair Test to Determine Vitamin D (3) Levels. Molecules 2021, 26, 3269.
10. Bouillon, R. Free or Total 25OHD as Marker for Vitamin D Status? J. Bone Miner. Res. 2016, 31, 1124-1127.
11. Kia, S.; Fazilati, M.; Salavati, H.; Bohlooli, S. Preparation of a novel molecularly imprinted polymer by the sol-gel process for solid phase extraction of vitamin D3. RSC Adv. 2016, 6, 31906-31914.
12. Deschasaux, M.; Souberbielle, J.C.; Andreeva, V.A.; Sutton, A.; Charnaux, N.; Kesse-Guyot, E.; Latino-Martel, P.; Druesne- Pecollo, N.; Szabo de Edelenyi, F.; Galan, P.; et al. Quick and Easy Screening for Vitamin D Insufficiency in Adults: A Scoring System to Be Implemented in Daily Clinical Practice. Medicine 2016, 95, e2783.
13. Kim, H.J.; Le, J.-H. Impedance Based Vitamin D Measurement Sensor and Algorithm for Human Wellness. Sens. Transducers 2017, 216, 1-7.
14. Binkley, N.; Borchardt, G.; Siglinsky, E.; Krueger, D. Does vitamin d metabolite measurement help predict 25(oh)d change following vitamin d supplementation? Endocr. Pract. Off. J. Am. Coll. Endocrinol. Am. Assoc. Clin. Endocrinol. 2017, 23, 432-441.
15. Hannemann, A.; Thuesen, B.H.; Friedrich, N.; Volzke, H.; Steveling, A.; Ittermann, T.; Hegenscheid, K.; Nauck, M.; Linneberg, A.; Wallaschofski, H. Adiposity measures and vitamin D concentrations in Northeast Germany and Denmark. Nutr. Metab. 2015, 12, 24.
16. Feiyun, C.; Yue, Y.; Zhang, Y.; Zhang, Z.; Zhou, H.S. Advancing Biosensors with Machine Learning. ACS Sens. 2020, 5, 33463364.
17. Raji, H.; Tayyab, M.; Sui, J.; Mahmoodi, S.R.; Javanmard, M. Biosensors and Machine Learning for Enhanced Detection, Stratification, and Classification of Cells: A Review. arXiv 2021, arXiv:2101.01866.
18. Lee, S.; Oncescu, V.; Mancuso, M.; Mehta, S.; Erickson, D. A smartphone platform for the quantification of vitamin D levels. Lab A Chip 2014, 14, 1437-1442.
19. Lahav, Y.; Goldstein, N.; Gepner, Y. Comparison of body composition assessment across body mass index categories by two multifrequency bioelectrical impedance analysis devices and dual-energy X-ray absorptiometry in clinical settings. Eur. J. Clin. Nutr. 2021, 75, 1275-1282.
20. Andreozzi, P.; Verrusio, W.; Viscogliosi, G.; Summa, M.L.; Gueli, N.; Cacciafesta, M.; Albanese, C.V. Relationship between vitamin D and body fat distribution evaluated by DXA in postmenopausal women. Nutrition 2016, 32, 687-692.
21. Orces, C. The Association between Body Mass Index and Vitamin D Supplement Use among Adults in the United States. Cureus 2019, 11, e5721.
22. Al Hayek, S.; Matar Bou Mosleh, J.; Ghadieh, R.; El Hayek Fares, J. Vitamin D status and body composition: A cross-sectional study among employees at a private university in Lebanon. BMC Nutr. 2018, 4, 31.
23. Vimaleswaran, K.S.; Berry, D.J.; Lu, C.; Tikkanen, E.; Pilz, S.; Hiraki, L.T.; Cooper, J.D.; Dastani, Z.; Li, R.; Houston, D.K.; et al. Causal relationship between obesity and vitamin D status: Bi-directional Mendelian randomization analysis of multiple cohorts. PLoS Med. 2013, 10, e1001383.
24. Mowry, D.A.; Costello, M.M.; Heelan, K.A. Association Among Cardiorespiratory Fitness, Body Fat, and Bone Marker Measurements in Healthy Young Females. J. Osteopath. Med. 2009, 109, 534-539.
25. Blum, M.; Dallal, G.E.; Dawson-Hughes, B. Body size and serum 25 hydroxy vitamin D response to oral supplements in healthy older adults. J. Am. Coll. Nutr. 2008, 27, 274-279.
26. Camozzi, V.; Frigo, A.C.; Zaninotto, M.; Sanguin, F.; Plebani, M.; Boscaro, M.; Schiavon, L.; Luisetto, G. 25- Hydroxycholecalciferol response to single oral cholecalciferol loading in the normal weight, overweight, and obese. Osteoporos. Int. A J. Establ. Result Coop. Between Eur. Found. Osteoporos. Natl. Osteoporos. Found. USA 2016, 27, 2593-2602.
27. Kim, J.; Park, H.J.; Sung, D.J. The Relationship between Plasma Vitamin D Concentration and Blood Pressure in Korean Middle- aged Males: A Cross-sectional Study. Iran. J. Public Health 2018, 47, 1767-1768.
28. Yonemura, K.; Fujimoto, T.; Fujigaki, Y.; Hishida, A. Vitamin D deficiency is implicated in reduced serum albumin concentrations in patients with end-stage renal disease. Am. J. Kidney Dis. Off. J. Natl. Kidney Found. 2000, 36, 337-344.
29. Akbas, E.M.; Gungor, A.; Ozcicek, A.; Akbas, N.; Askin, S.; Polat, M. Vitamin D and inflammation: Evaluation with neutrophil- to-lymphocyte ratio and platelet-to-lymphocyte ratio. Arch. Med Sci. AMS 2016, 12, 721-727.
30. Kang, J.H.; Kim, S.S.; Moon, S.S.; Kim, W.J.; Bae, M.J.; Choi, B.G.; Jeon, Y.K.; Kim, B.H.; Kim, Y.K.; Kim, I.J. Adiposity in the Relationship between Serum Vitamin D Level and Insulin Resistance in Middle-Aged and Elderly Korean Adults: The Korea National Health and Nutrition Examination Survey 2008. Endocrinol. Metab. 2013, 28, 96-102.
31. Sawicki, C.M.; Van Rompay, M.I.; Au, L.E.; Gordon, C.M.; Sacheck, J.M. Sun-Exposed Skin Color is Associated with Changes in Serum 25-Hydroxyvitamin D in Racially/Ethnically Diverse Children. J. Nutr. 2016, 146, 751-757.
32. Lukaszuk, J.M.; Prawitz, A.D.; Johnson, K.N.; Umoren, J.; Bugno, T.J. Development of a Noninvasive Vitamin D Screening Tool. Fam. Consum. Sci. Res. J. 2012, 40, 229-240.
33. Sari, D.K.; Sari, L.M.; Laksmi, L.I.F. The Moderate Correlation Between 25(OH)D Serum and Saliva in Healthy People with Low Vitamin D Intake. Int. J. Gen. Med. 2021, 14, 841-850.
34. Krul-Poel, Y.H.M.; Agca, R.; Lips, P.; van Wijland, H.; Stam, F.; Simsek, S. Vitamin D status is associated with skin autofluorescence in patients with type 2 diabetes mellitus: A preliminary report. Cardiovasc. Diabetol. 2015, 14, 89.
35. Sambasivam, G.; Amudhavel, J.; Sathya, G. A Predictive Performance Analysis of Vitamin D Deficiency Severity Using Machine Learning Methods. IEEE Access 2020, 8, 109492-109507.
36. Ene, C.D.; Anghel, A.E.; Neagu, M.; Nicolae, I. 25-OH Vitamin D and Interleukin-8: Emerging Biomarkers in Cutaneous Melanoma Development and Progression. Mediat. Inflamm. 2015, 2015, 904876.
37. Al-Eisa, E.S.; Alghadir, A.H.; Gabr, S.A. Correlation between vitamin D levels and muscle fatigue risk factors based on physical activity in healthy older adults. Clin. Interv. Aging 2016, 11, 513-522.
38. Gradillas-García, A.; Alvarez, J.; Rubio, J.A.; de Abajo, F.J. Relationship between vitamin D deficiency and metabolic syndrome in adult population of the Community of Madrid. Endocrinol. Y Nutr. Organo De La Soc. Esp. De Endocrinol. Y Nutr. 2015, 62, 180187.

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Observations by Founder of Vitamin D Life (formerly an Instrumentation Engineer)

I designed and built devices that measured a wide range of parameters for >20 years
This study experimented with a wide range of frequencies to measure skin impedance and found 21Hz the best correlation to Vitamin D
Additional potential measurement inputs include:

• Phase Angle
• Compare Impedance at two different amplitudes
• Compare Impedance at two different frequencies
• Compare Impedance measured with different waveforms (sinusoid, square, pulse, etc)
• Measure impedance using impulse response, rather than continuous waveform

There are a wide variety of analysis techniques
There are a wide variety of sources of interference not mentioned in this study- such as

• sweat
• hydration level
• Ratio of body fat to muscle

Skin impedance appears to have the potential to roughly determine Vitamin D levels, but it is years in the future

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Vitamin D estimation using Machine Learning (One of the references)

A Predictive Performance Analysis of Vitamin D Deficiency Severity Using Machine Learning Methods - IEEE, June 2020

Many Machine Learning Techniques provide OK accuracy

 Download the PDF from Vitamin D Life

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Vitamin D Life - Tests for Vitamin D contains:

• Fact: Many countries no longer pay for more than 1 (some not pay for even a single Vit D test)
    They feel that Vit D testing is not needed except for a few conditions (Rickets, etc) Japan is an exception
• Fact: Vit D tests are not very accurate
     The best lab tests have accuracies and repeatabilities of +-5 ng
     Low cost vitamin D Blood Tests - both in lab and at home
     Many lab tests have accuracies and repeatabilities of +- 10 ng - or worse
     Vitamin D deficiency of a group - 15% to 48%
• Fact: Low-cost office/home Vit D tests are available around the world (not US as of 2018)
     Low-cost 35 ng Y/N test by Nanospeed
     Low-cost Vitamin D testers (two yes-no tests for 42 dollars) - 2023 Nanospeed
     Quick, free, self test for deficiency
• Fact: 3 major Vit D gene problems are not noticed by Vit D tests
     ~ 20% of people have poor Vit D genes
     Hint that Vit D not getting to cells: Vit D related diseases run in your family
     Another hint - you have one of the 40 diseases which are 2X more likely if have poor genes
• Fact: A Vit D test will rarely (<1 in 1000) indicate that you are getting too much
• Opinion: If only getting a single test, wait till after supplementing with Vit D
     3 months after starting a maintenance dose or 4 weeks after a loading dose