I-Well™

For Trained Immunity*

• Beta-1,3-glucan primes, strengthens, and maintains healthy immunity.
• Solid lipid curcumin particles promote a healthy inflammatory response, neurological health, and cardiovascular health.
• Vitamin D3 supplies a required micronutrient for optimal inflammatory response.
• EGCG supports cellular, cardiovascular, brain, and metabolic health.

Beta-1,3-glucan — A Very Big Deal

Primes, strengthens, and maintains healthy immunity.

Beta-1,3-glucan is a non-digestible polysaccharide isolated from Euglena gracilis algae. It's well established that beta-1,3-glucan acts as an immunomodulatory agent.

This means the body's pattern-recognition receptors (PPRs; Dectin-1) identify beta-1,3-glucan as "non-self" or foreign, which activates healthy immune responses. Triggering these responses with beta-1,3-glucan can prime, strengthen, and support sustained healthy immune function (1-17).

Beta-1,3-glucan also fuels the growth of good bacteria (lactobacillus and bifidobacteria) in the gut, and supports the health of intestinal cells that act as a protective physical barrier (15, 16).

There's nothing else like it. Beta-1,3-glucan is a breakthrough for anyone wanting to maintain a strong, healthy immune system — it's a very big deal.

Curcumin's Great Potential Realized

Promotes a healthy inflammatory response, and supports neurological and cardiovascular health.

Medical researchers have had a longtime interest in curcumin for its positive effects on inflammatory response, neurological health, and cardiovascular health.

But the frustrating problem has always been its poor bioavailability. Curcumin isn't soluble in the gastrointestinal tract, making it difficult to absorb, and it's vulnerable to something called glucuronidation, which converts curcumin into what amounts to inactive waste.

An example of curcumin's poor bioavailability is a study where patients were given a whopping 3.6 grams of ordinary curcumin a day (about 7 capsules). Even at those large doses, detectable blood and liver levels of free-form curcumin were almost non-existent (18).

Absorb 95X More Curcumin*

There is a solution for optimal curcumin uptake. Research shows solid lipid curcumin particles produce 95 times more free curcumin in the bloodstream than highly pure, standardized curcumin (Gota VS et al, 2010).*

That's a bold claim. Fortunately, solid lipid curcumin particles are backed up with convincing science, invented by neuroscientists at UCLA, funded by the University of California (Oakland) and the Federal Government, supported by peer-reviewed research on humans, and patented (9,192,644).

Microencapsulated Vitamin D3

Supplies a required micronutrient for optimal inflammatory response.

Research shows Vitamin D3 (choleocalciferol) is a required micronutrient for maintaining an optimal inflammatory response and healthy immune system (40-44).

Unfortunately, vitamin D deficiencies are rampant, especially in the areas with the least exposure to the sun. That's because the body naturally produces Vitamin D when skin has direct exposure to sunlight. Adding to the problem, it's difficult to absorb enough D3 in our diets.

Without proper or optimal vitamin D levels, T cells aren't effective and flat out don't activate (40). To make matters worse, it's really difficult to achieve or maintain adequate levels of D3 with most supplementation (45).

The I-Well™ formula contains microencapsulated vitamin D3, which presents as tiny, water dispersible "beadlets" that enhance uptake.

Studies show that this microencapsulated form is the most bioavailable and longest lasting. Its effects remain constant for up to 14 days, making it clearly superior to the oil-based vitamin D3 supplements that make up most of the market (45).

Epigallocatechin-3-Gallate (EGCG)

Supports cardiovascular, brain, metabolic, and cellular health.

EGCG (epigallocatechin-3-gallate) is a powerful health-promoting polyphenol found in green tea — having positive effects on the body's inflammation response and on various target tissues (46-54).

A host of studies (mostly in vitro) show EGCG has protective effects on the cardiovascular (47, 48) and nervous systems (47, 52-54). It promotes cellular health (50, 52), and stimulates metabolic function (48, 49).

SUPPLEMENT FACTS

Servings Size 3 Capsules
Servings Per Container 30

Amount Per Serving % Daily Value

Vitamin D3 (as cholecalciferol) 125 mcg (5,000 IU) 625%

Beta-1,3-glucan (from Euglena gracilis whole algae extract) 400 mg†

Solid lipid curcumin particles (from turmeric rhizome extract) 400 mg†

EGCG (epigallocatechin gallate from Camellia sinensis leaf extract) 400 mg†

† Daily Value not established.

Other Ingredients: Rice flour, hypromellose (vegetable capsule), rice hull concentrate, L-leucine.

• Take three capsules once per day with food, preferably the largest meal of the day.

Beta-1,3-glucan

1. Moorlag S et al. β-Glucan Induces Protective Trained Immunity against Mycobacterium tuberculosis Infection: A Key Role for IL-1 Cell Reports 31, 107634, May 19, 2020. DOI: doi.org/10.1016/j.celrep.2020.107634.
2. Del Cornò M et al. Shaping the Innate Immune Response by Dietary Glucans: Any Role in the Control of Cancer? Cancers 2020, 12, 15. DOI: 10.3390/cancers12010155.
3. Borchani C et al. Structural Characterization, Technological Functionality, and Physiological Aspects of Fungal B-D-glucans: A Review. Crit Rev Food Sci Nutr, 56(10:1746-52, PMIC 25830657, Jul 2016.
4. Vetvicka V, Vetvickova I. Glucans and Cancer: Comparison of Commercially Available B-glucans – Part IV. Anticancer Res, 38(3):1327-1333, Mar 2018.
5. Davis JM et al. Effects of oat beta-glucan on innate immunity and infection after exercise stress. Med Sci Sports Exerc. 2004, Aug;36(8):1321-7.
6. Volman JJ et al. Dietary modulation of immune function by β-glucans. Physiology & Behavior, Volume 94, Issue 2, 23 May 2008, Pages 276-284.
7. Rondanelli M et al. The biological activity of beta-glucans. Minerva Med. 2009 Jun;100(3):237-45.
8. Vetvicka V, Vetvickova J. β-Glucan Improves Conditions of Chronic Fatigue in Mice by Stimulation of Immunity. The Open Biochemistry Journal, 2-18-2020.
9. Akramiene D et al. Effects of ß-glucans on the immune system. Medicinia, 11 August 2007.
10. Graugaum HJ et al. A double-blind, randomized, placebo-controlled nutritional study using an insoluble yeast beta-glucan to improve the immune defense system. Dood Nutr Sci, 3(6):738-746, June 2012.
11. Carlos AF et al. β-Glucan successfully stimulated the immune system in different jawed vertebrate species. Comparative Immunology, Microbiology and Infectious Diseases, Volume 62, February 2019, Pages 1-6.
12. Garcia-Valtanen p et al. Evaluation of trained immunity by β-1, 3 (D)-glucan on murine monocytes in vitro and duration of response in vivo. Immunology and Cell Biology (2017) 95, 601–610; DOI: 10.1038/icb.2017.13.
13. Paris S et al. β-Glucan-Induced Trained Immunity in Dogs. Front. Immunol. 09 October 2020. 11:566893. DOI: 10.3389/fimmu.2020.566893.
14. Byrne K et al. Differential induction of innate memory in porcine monocytes by b-glucan or bacillus Calmette-Guerin. Innate Immunity. 0(0) 1–13. 2020. DOI: 10.1177/1753425920951607.
15. Petit J et al. Long-lived effects of administering b-glucans: Indications for trained immunity in fish. Developmental and Comparative Immunology 64 (2016) 93e102. 2016. DOI: dx.doi.org/10.1016/j.dci.2016.03.003.
16. Kwanghook, K et al. Algae-derived β-glucan enhanced gut health and immune responses of weaned pigs experimentally infected with a pathogenic E. coli. Animal Feed Science and Technology, Volume 248, February 2019.
17. Abraham A et al. A novel vaccine platform using glucan particles for induction of protective responses against Francisella tularensis and other pathogens. Clinical and Experimental Immunology, 198: 143–152. 2019. DOI: 10.1111/cei.13356.

Curcumin

18. Gota VS et al. Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers. J Agric Food Chem. 2010 Feb 24;58(4):2095-9. DOI: 10.1021/jf9024807.
19. Cox KHM et al. Further evidence of benefits to mood and working memory from lipidated curcumin in healthy older people: A 12-week, double-blind, placebo-controlled, partial replication study. Nutrients. 2020 Jun 04. 12(6): 1678. DOI: 10.3390/nu12061678.
20. Esfahani K et al. A phase I open prospective cohort trial of curcumin plus tyrosine kinase inhibitors for EGFR-mutant advanced non-small cell lung. J Clin Oncol. 2019. 37(15_suppl): e20611-e20611. DOI: 10.1200/JCO.2019.37.15_suppl.e20611.
21. Scholey A et al. Curcumin improves hippocampal function in healthy older adults: A three month randomized controlled trial. Poster Presentation in: 13th European Nutrition Conference — Malnutrition in an Obese World: European Perspectives (FENS). Dublin, Ireland. 2019: P3-01-02.
22. Scholey A et al. A highly bioavailable curcumin extract improves neurocognitive function and mood in healthy older people: A 12-week randomized, double-blind, placebo-controlled trial (OR32-05-19). Current Dev Nut. 2019 Jun. Poster Presentation. Volume 3(Issue Supplement 1): nzz052.OR32–05–19. DOI: 10.1093/cdn/nzz052.OR32-05-19.
23. Gupte PA et al. Evaluation of the efficacy and safety of capsule solid lipid curcumin particles in knee: A pilot clinical study. J Inflamm Res. 2019. 12: 145-152. DOI: 10.2147/JIR.S205390.
24. Koronyo, Y et al. Retinal amyloid pathology and proof-of-concept imaging trial. JCI Insight. 2017. 2(16). DOI: 10.1172/jci.insight.93621.
25. Santos-Parker JR et al. Curcumin supplementation improves vascular endothelial function in healthy middle-aged and older adults by increasing nitric oxide bioavailiability and reducing oxidative stress. Aging. 2017 Jan. 3. Vol 9(No1): 187-208.
26. McFarlin et al. Reduced inflammatory and muscle damage biomarkers following oral supplementation with bioavailable curcumin. University of North Texas. BBA Clinical. 2016 Feb 18. 5: 72-78. DOI: 10.1016/j.bbacli.2016.02.003.
27. Santos-Parker JR et al. Curcumin supplement improves vascular endothelial function in middle-aged and older adults. Geront. 2015 Dec. 55(Suppl 2): 195. DOI: 10.1093/geront/gnv554.01.
28. Rafii MS et al. The biomarker initiative DSBI pilot: Proof of concept for deep phenotyping of biomarkers. Front Behav Neurosci. 2015. 9: 1-11.
29. Cox KH et al. Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older population. Centre for Human Psychopharmacology, Swinburne University. J Psychopharmacol. 2015 May. Vol 29(No 5): 642-651. DOI: 10.1177/0269881114552744.
30. Hazarey VK et al. Efficacy of curcumin in the treatment for oral health – A randomized clinical trial. Government Dental College and Hospital. Nagpur, Maharashtra, India. J Oral Maxillofac Pathol. 2015. 19: 145-52. DOI: 10.4103/0973-029X.164524.
31. Machida N et al. Effects of Solid, Lipid Curcumin Particles on alcohol metabolism — An expiatory and a randomized, double-blind, placebo-controlled, parallel-group crossover study. Jpn Pharmacol Ther. 2020 Apr. 48(5): 867-873.
32. Frost S et al. Retinal amyloid fluorescence imaging predicts cerebral amyloid burden. Alz Dement. 2014. 10(4): P234-P235.
33. DiSilvestro et al. Diverse effects of a low-dose supplement of lipidated curcumin in healthy middle-aged people. The Ohio State University. Nutr. J. 2012 Sep 26. 11(79). DOIi: 10.1186/1475-2891-11-79.
34. Khattry N et al. Curcumin decreases cytokine levels involved in mucositis in autologous transplant setting: A pharmacokinetic-pharmacodynamic study. Poster presented at 54th American Society of Hematology (ASH) Annul Meeting. Atlanta, GA. 2012 Dec 08. Blood. 120(21): 3039.
35. Shah et al. Acute human pharmacokinetics of a lipid-dissolved turmeric extract. Planta Med. 2012. 48-PH5.
36. Pharmacokinetics of [lipidated curcumin]: Dose-concentration correlation. Unpublished, UCLA 2011-2012.
37. Gota et al. Safety and pharmacokinetics of a solid lipid curcumin particle formulation in patients and healthy volunteers. Tata Memorial Cancer Centre. J Ag Food Chem. 2010. 58(4): 2095-2099.
38. [Lipidated curcumin] binds to amyloid in human CNS after a single dose. Unpublished.
39. A phase 1 open-label prospective cohort trial of curcumin plus tyrosin kinase inhibitors for EGFR-mutant advanced NSCLC. McGill U & Jewish General Hospital, Canada. Ongoing.

Vitamin D3

40. Aranow C. Vitamin D and the Immune System. J Investigative Medicine, 2011 Aug;59(6):881-886.
41. Autier P, Gandini S. Vitamin D Supplementation and Total Mortality: A Meta-analysis of Randomized Controlled Trials. Arch Intern Med. Sept. 10, 2007;167(16):1730-1737.
42. Adit A et al. Association Between Serum 25-Hydroxyvitamin D Level and Upper Respiratory Tract Infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2009;169(4):384-390.
43. Marineua AR et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ, 15 February 2017.
44. Urshima M et al. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr. 2010, May;91(5):1255-60.
45. Simoliunas E et al. Bioavailability of Different Vitamin D Oral Supplements in Laboratory Animal Model. Medicina, 2019, 55(6), 265. 2597 C.

EGCG (Epigallocatechin-3-gallate)

46. Chu C et al. Green Tea Extracts Epigallocatechin-3-gallate for Different Treatments. Biomed Research International. Volume 2017, 13 Aug.
47. Kishimoto Y et al. Pleiotropic preventive effects of dietary polyphenols in cardiovascular diseases. European Journal of Clinical Nutrition, vol. 67, no. 5, pp. 532–535, 2013.
48. Qian Yi Eng et al. Molecular understanding of Epigallocatechin gallate (EGCG) in cardiovascular and metabolic diseases. Journal of Ethnopharmacology, Volume 210, 10 January, 2018, pp. 296-310.
49. Xu Y et al. Inhibition of Tobacco-specific Nitrosamine-induced Lung Tumorigenesis in A/J Mice by Green Tea and Its Major Polyphenol as Antioxidants. Cancer Research, Published July 1992.
50. Jung YD et al. EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells. British Journal of Cancer, vol. 84, no. 6, pp. 844–850, 2001.
51. Guang-Jian Du et al. Epigallocatechin Gallate (EGCG) Is the Most Effective Cancer Chemopreventive Polyphenol in Green Tea. Nutrients 2012, 4(11), 1679-1691.
52. Mandel S et al. Multifunctional Activities of Green Tea Catechins in Neuroprotection. Neurosignals. 2005;14(1-2):46-60. DOI: 10.1159/000085385.
53. Biasibetti R et al. Green tea (-)epigallocatechin-3-gallate reverses oxidative stress and reduces acetylcholinesterase activity in a streptozotocin-induced model of dementia. Behav Brain Res. 2013 Jan 1. DOI: 10.1016/j.bbr.2012.08.039.
54. Rasoolijazi H et al. The Beneficial Effect of (-)-Epigallocatechin-3-Gallate in an Experimental Model of Alzheimer’s Disease in Rat: a Behavioral Analysis. Iranian Biomedical Journal. October 2007.