Vitamin D3 (as Cholecalciferol), Folate [as L-Methylfolate (5-MTHF)], Vitamin B12 (as Methylcobalamin), Proprietary Blend: Astragalus (Astragalus propinquus; Root; 4:1 Extract), Fo-Ti Extract (Fallopia multiflora; Root), Holy Basil Extract (Ocimum sanctum; Leaf), Ashwagandha (Withania somnifera; Root; 4:1 Extract), Drynaria Rhizome, Rubus chingii Hu Extract (Root), Rhodiola (Rhodiola rosea; Root; 4:1 Extract), Blueberry Fruit Powder, L-Theanine HCI, Pterocarpus marsupium Extract (Bark), Haritaki Extract (Terminalia chebula; Fruit), BioPerine® (Black Pepper Extract; Piper nigrum; Fruit), Pine Bark Extract (Pinus massoniana), Genistein. Other Ingredients: Methylcellulose Capsule.

Adults take 1 capsule daily with 8 ounces of water or your favorite beverage. May be taken with or without food.

CAUTION: Do not exceed recommended dose. Pregnant, nursing mothers, children under 18 and individuals with a known medical condition should consult a physician before using this or any dietary supplement. Please use caution if you have allergies or sensitivities to any of the listed ingredients. Keep out of reach of children and pets. Do not use if safety seal is damaged or missing. Store in a cool dry place. Use this product as a food supplement only. Do not use for weight reduction.

Vitamin 5-MTHF

Rodan LH, Qi W, Ducker GS, et al. 5,10-methenyltetrahydrofolate synthetase deficiency causes a neurometabolic disorder associated with microcephaly, epilepsy, and cerebral hypomyelination. Mol Genet Metab. 2018;125(1-2):118-126. doi: 10.1016/j.ymgme.2018.06.006

Misselbeck K, Marchetti L, Priami C, Stover PJ, Field MS. The 5-formyltetrahydrofolate futile cycle reduces pathway stochasticity in an extended hybrid-stochastic model of folate-mediated one-carbon metabolism. Sci Rep. 2019;9(1):4322. Published 2019 Mar 13. doi: 10.1038/s41598-019-40230-4

Scaglione, F., & Panzavolta, G. (2014). Folate, folic acid and 5-methyltetrahydrofolate are not the same thing. Xenobiotica; the fate of foreign compounds in biological systems, 44(5), 480–488. DOI: 10.3109/00498254.2013.845705

Akoglu, B., Schrott, M., Bolouri, H. et al. The folic acid metabolite L-5-methyltetrahydrofolate effectively reduces total serum homocysteine level in orthotopic liver transplant recipients: a double-blind placebo-controlled study. Eur J Clin Nutr 62, 796–801 (2008). DOI: 10.1093/ajcn/77.3.658

Cochrane, K. M., Mayer, C., Devlin, A. M., Elango, R., Hutcheon, J. A., & Karakochuk, C. D. (2020). Is natural (6S)-5-methyltetrahydrofolic acid as effective as synthetic folic acid in increasing serum and red blood cell folate concentrations during pregnancy? A proof-of-concept pilot study. Trials, 21(1), 380. DOI: 10.1186/s13063-020-04320-3

Vitamin Methyl B12

Lin, C. Y., Kuo, C. S., Lu, C. L., Wu, M. Y., & Huang, R. F. (2010). Elevated serum vitamin B(12) levels in association with tumor markers as the prognostic factors predictive for poor survival in patients with hepatocellular carcinoma. Nutrition and cancer, 62(2), 190–197. DOI: 10.1080/01635580903305334

Majaj A. S. (1966). Vitamin E-responsive macrocytic anemia in protein-calorie malnutrition. Measurements of vitamin E, folic acid, vitamin C, vitamin B12 and iron. The American journal of clinical nutrition, 18(5), 362–368. DOI: 10.1093/ajcn/18.5.362

Kwok, T., Tang, C., Woo, J., Lai, W. K., Law, L. K., & Pang, C. P. (1998). Randomized trial of the effect of supplementation on the cognitive function of older people with subnormal cobalamin levels. International journal of geriatric psychiatry, 13(9), 611–616. DOI: 10.1002/(sici)1099-1166(199809)13:9<611::aid-gps832>3.0.co;2-o

Lonn, E., Yusuf, S., Arnold, M. J., Sheridan, P., Pogue, J., Micks, M., McQueen, M. J., Probstfield, J., Fodor, G., Held, C., Genest, J., Jr, & Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators (2006). Homocysteine lowering with folic acid and B vitamins in vascular disease. The New England journal of medicine, 354(15), 1567–1577. DOI: 10.1056/NEJMoa060900

Kwok, T., Lee, J., Law, C. B., Pan, P. C., Yung, C. Y., Choi, K. C., & Lam, L. C. (2011). A randomized placebo controlled trial of homocysteine lowering to reduce cognitive decline in older demented people. Clinical nutrition (Edinburgh, Scotland), 30(3), 297–302. DOI: 10.1016/j.clnu.2010.12.004

Clarke R. (2000). Lowering blood homocysteine with folic acid-based supplements: meta-analysis of randomised trials. Indian heart journal, 52(7 Suppl), S59–S64. PMID: 11339443

Ma, E., Iwasaki, M., Kobayashi, M., Kasuga, Y., Yokoyama, S., Onuma, H., Nishimura, H., Kusama, R., & Tsugane, S. (2009). Dietary intake of folate, vitamin B2, vitamin B6, vitamin B12, genetic polymorphism of related enzymes, and risk of breast cancer: a case-control study in Japan. Nutrition and cancer, 61(4), 447–456. DOI: 10.1080/01635580802610123

Malouf, R., & Areosa Sastre, A. (2003). Vitamin B12 for cognition. The Cochrane database of systematic reviews, (3), CD004326. DOI: 10.1002/14651858.CD004326

Malouf, R., & Grimley Evans, J. (2008). Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people. The Cochrane database of systematic reviews, (4), CD004514. DOI: 10.1002/14651858.CD004514.pub2

McNulty, H., Pentieva, K., Hoey, L., & Ward, M. (2008). Homocysteine, B-vitamins and CVD. The Proceedings of the Nutrition Society, 67(2), 232–237. DOI: 10.1017/S0029665108007076

Chen, K. J., Pan, W. H., Yang, F. L., Wei, I. L., Shaw, N. S., & Lin, B. F. (2005). Association of B vitamins status and homocysteine levels in elderly Taiwanese. Asia Pacific journal of clinical nutrition, 14(3), 250–255. PMID: 16169836

13 Potent Herbal Extracts

Chandrasekhar, K., Kapoor, J., & Anishetty, S. (2012). A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of Ashwagandha root in reducing stress and anxiety in adults. Indian Journal of Psychological Medicine, 34(3), 255–262. doi: 10.4103/0253-7176.106022

BHATIA, V. and TANDON, R.K. (2005), Stress and the gastrointestinal tract. Journal of Gastroenterology and Hepatology, 20: 332-339. doi:10.1111/j.1440-1746.2004.03508.x

Singh SK, Rajoria K. Ayurvedic management of chronic constipation in Hirschsprung disease - A case study. J Ayurveda Integr Med. 2018;9(2):131–135. doi: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033722/

Mishra, L.C. & Singh, B.B. & Dagenais, Simon. (2000). Scientific basis for the therapeutic use of Withania somnifera (Ashwagandha): A Review. Alternative medicine review : a journal of clinical therapeutic. 5. 334-46. PMID: 10956379

Shahzad, M., Shabbir, A., Wojcikowski, K., Wohlmuth, H., & Gobe, G. C. (2016). The Antioxidant Effects of Radix Astragali (Astragalus membranaceus and Related Species) in Protecting Tissues from Injury and Disease. Current drug targets, 17(12), 1331–1340. DOI: 10.2174/1389450116666150907104742

Li, X., Qu, L., Dong, Y., Han, L., Liu, E., Fang, S., Zhang, Y., & Wang, T. (2014). A review of recent research progress on the astragalus genus. Molecules (Basel, Switzerland), 19(11), 18850–18880. DOI: 10.3390/molecules191118850

Fernández-Lázaro, D., Mielgo-Ayuso, J., Córdova Martínez, A., & Seco-Calvo, J. (2020). Iron and Physical Activity: Bioavailability Enhancers, Properties of Black Pepper (Bioperine^®) and Potential Applications. Nutrients, 12(6), 1886. DOI: 10.3390/nu12061886

Peterson, C. T., Vaughn, A. R., Sharma, V., Chopra, D., Mills, P. J., Peterson, S. N., & Sivamani, R. K. (2018). Effects of Turmeric and Curcumin Dietary Supplementation on Human Gut Microbiota: A Double-Blind, Randomized, Placebo-Controlled Pilot Study. Journal of evidence-based integrative medicine, 23, 2515690X18790725. DOI: 10.1177/2515690X18790725

Panahi, Y., Khalili, N., Hosseini, M. S., Abbasinazari, M., & Sahebkar, A. (2014). Lipid-modifying effects of adjunctive therapy with curcuminoids-piperine combination in patients with metabolic syndrome: results of a randomized controlled trial. Complementary therapies in medicine, 22(5), 851–857. DOI: 10.1016/j.ctim.2014.07.006

Jamshidi N, Cohen MM. The Clinical Efficacy and Safety of Tulsi in Humans: A Systematic Review of the Literature. Evid Based Complement Alternat Med. 2017;2017:9217567. doi: 10.1155/2017/9217567

Cohen MM. Tulsi - Ocimum sanctum: A herb for all reasons. J Ayurveda Integr Med. 2014;5(4):251-259. doi: 10.4103/0975-9476.146554

Vitamin D3

Lips P. (2006). Vitamin D physiology. Progress in biophysics and molecular biology, 92(1), 4–8. DOI: 10.1016/j.pbiomolbio.2006.02.016

Sinha, Akash & Hollingsworth, Kieren & Ball, Steve & Cheetham, Tim. (2013). Improving the vitamin D status of vitamin D deficient adults is associated with improved mitochondrial oxidative function in skeletal muscle. Endocrine Abstracts. 1-1. DOI: 10.1530/endoabs.31.OC1.6

Roy S, Sherman A, Monari-Sparks MJ, Schweiker O, Hunter K. Correction of Low Vitamin D Improves Fatigue: Effect of Correction of Low Vitamin D in Fatigue Study (EViDiF Study). N Am J Med Sci. 2014;6(8):396-402. doi: 10.4103/1947-2714.139291

Nowak A, Boesch L, Andres E, et al. Effect of vitamin D3 on self-perceived fatigue: A double-blind randomized placebo-controlled trial [published correction appears in Medicine (Baltimore). 2017 Jan 20;96(3):e6038]. Medicine (Baltimore). 2016;95(52):e5353. doi: 10.1097/MD.0000000000005353

Ellis SD, Kelly ST, Shurlock JH, Hepburn ALN. The role of vitamin D testing and replacement in fibromyalgia: a systematic literature review. BMC Rheumatol. 2018;2:28. Published 2018 Oct 5. doi: 10.1186/s41927-018-0035-6

Rai, S. K., Gupta, T. P., Kashid, M., Shaki, O., Chakrabarty, B. K., & Upreti, V. (2020). Can self-perceived easy fatigability be a predictor of vitamin D deficiency in young Indian women?. Journal of family medicine and primary care, 9(2), 997–1002. DOI: 10.4103/jfmpc.jfmpc_862_19

Ghai, B., Bansal, D., Kapil, G., Kanukula, R., Lavudiya, S., & Sachdeva, N. (2015). High Prevalence of Hypovitaminosis D in Indian Chronic Low Back Patients. Pain physician, 18(5), E853–E862. PMID: 26431139

Stratton-Loeffler, M. J., Lo, J. C., Hui, R. L., Coates, A., Minkoff, J. R., & Budayr, A. (2012). Treatment of vitamin D deficiency within a large integrated health care delivery system. Journal of managed care pharmacy : JMCP, 18(7), 497–505. DOI: 10.18553/jmcp.2012.18.7.497

Cuppari, L., & Garcia-Lopes, M. G. (2009). Hypovitaminosis D in chronic kidney disease patients: prevalence and treatment. Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation, 19(1), 38–43. DOI: 10.1053/j.jrn.2008.10.005

Havdahl A, Mitchell R, Paternoster L, Davey Smith G. Investigating causality in the association between vitamin D status and self-reported tiredness. Sci Rep. 2019;9(1):2880. Published 2019 Feb 27. doi: 10.1038/s41598-019-39359-z

Annweiler, C., & Beauchet, O. (2015). Questioning vitamin D status of elderly fallers and nonfallers: a meta-analysis to address a 'forgotten step'. Journal of internal medicine, 277(1), 16–44. DOI: 10.1111/joim.12250

Mesinovic, J., Mousa, A., Wilson, K., Scragg, R., Plebanski, M., de Courten, M., Scott, D., Naderpoor, N., & de Courten, B. (2019). Effect of 16-weeks vitamin D replacement on calcium-phosphate homeostasis in overweight and obese adults. The Journal of steroid biochemistry and molecular biology, 186, 169–175. DOI: 10.1016/j.jsbmb.2018.10.011

Bjelakovic, G., Gluud, L. L., Nikolova, D., Whitfield, K., Wetterslev, J., Simonetti, R. G., Bjelakovic, M., & Gluud, C. (2014). Vitamin D supplementation for prevention of mortality in adults. The Cochrane database of systematic reviews, (1), CD007470. DOI: 10.1002/14651858.CD007470.pub3

Jelsness-Jørgensen LP, Grøvle L, Julsrud Haugen A. Association between vitamin D and fatigue in patients with rheumatoid arthritis: a cross-sectional study. BMJ Open. 2020;10(2):e034935. Published 2020 Feb 6. doi: 10.1136/bmjopen-2019-034935

Pennisi M, Malaguarnera G, Di Bartolo G, et al. Decrease in Serum Vitamin D Level of Older Patients with Fatigue. Nutrients. 2019;11(10):2531. Published 2019 Oct 20. doi: 10.3390/nu11102531

Annema W, Nowak A, von Eckardstein A, Saleh L. Evaluation of the new restandardized Abbott Architect 25-OH Vitamin D assay in vitamin D-insufficient and vitamin D-supplemented individuals. J Clin Lab Anal. 2018;32(4):e22328. doi: 10.1002/jcla.22328

Ahmadieh, H., & Arabi, A. (2011). Vitamins and bone health: beyond calcium and vitamin D. Nutrition reviews, 69(10), 584–598. DOI: 10.1111/j.1753-4887.2011.00372.x