Fasting Formula 

Our fasting formula, to be taken during your daily fasting window includes ingredients which will upregulate autophagy further to clear the spike protein. Each two capsule serving includes ingredients which have been associated with autophagy upregulation in scientific studies.

Magnesium bis-glycinate

As one of the most bio-available forms of magnesium, this supplement is more likely to be absorbed and ultimately used by the body when compared to other, less bioavailable forms of magnesium [1]. Magnesium deficiency (measured by a low magnesium to calcium ratio) is correlated greater risk of mortality in acute Covid-19[1], and magnesium deficiency is also associated with a higher risk of Covid-19 infection [3]. Magnesium is a crucial factor in many biological processes [4], and several processes important for recovery from Covid-19 [5,6].

[1] Pardo, Marta R., et al. "Bioavailability of magnesium food supplements: A systematic review." Nutrition 89 (2021): 111294.

[2] Guerrero-Romero, Fernando, et al. "Magnesium-to-calcium ratio and mortality from COVID-19." Nutrients 14.9 (2022): 1686.

[3] Tian, Jing, et al. "Populations in low-magnesium areas were associated with higher risk of infection in COVID-19’s early transmission: a nationwide retrospective cohort study in the United States." Nutrients 14.4 (2022): 909.

[4] Schwalfenberg, Gerry K., and Stephen J. Genuis. "The importance of magnesium in clinical healthcare." Scientifica 2017 (2017).

[5] Iotti, Stefano, et al. "The COVID-19 pandemic: is there a role for magnesium? Hypotheses and perspectives." Magnesium Research 33.2 (2020).

[6] Tang, Chuan-Feng, et al. "Possibility of magnesium supplementation for supportive treatment in patients with COVID-19." European journal of pharmacology 886 (2020): 173546.

Resveratrol

Resveratrol has been identified as an agent which can improve rates of autophagy [7,8]. As autophagy is a means by which our bodies break down proteins (including the spike protein), resveratrol may improve outcomes in Covid-19 [9]. In addition to the role on autophagy, resveratrol also has anti-inflammatory and anti-thrombotic (i.e. clots) impacts[10]. A trial on resveratrol for Covid-19 demonstrated that the treatment group receiving resveratrol had a 33% the rate of hospitalization, 57% the rate of Covid-19 related emergency room visits and 50% of the rate of pneumonia as the control group not receiving resveratrol [11].

Though this was a small study, it is promising, and supports in vitro evidence where resveratrol inhibited SARS-CoV-2 replication, as well as a related coronavirus (HcoV-229E), while having limited toxicity to the cells themselves [12]. 

[7] Morselli, Eugenia, et al. "Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome." Journal of Cell Biology 192.4 (2011): 615-629.

[8] Ferraresi, Alessandra, et al. "The protein restriction mimetic Resveratrol is an autophagy inducer stronger than amino acid starvation in ovarian cancer cells." Molecular Carcinogenesis 56.12 (2017): 2681-2691.

[9] Domi, Elisa, et al. "The importance of nutraceuticals in COVID-19: What’s the role of resveratrol?." Molecules 27.8 (2022): 2376.

[10] Giordo, Roberta, et al. "Therapeutic potential of resveratrol in COVID-19-associated hemostatic disorders." Molecules 26.4 (2021): 856.

[11] McCreary, Marvin R., Patrick M. Schnell, and Dale A. Rhoda. "Randomized double-blind placebo-controlled proof-of-concept trial of resveratrol for outpatient treatment of mild coronavirus disease (COVID-19)." Scientific Reports 12.1 (2022): 10978.

[12] Pasquereau, Sébastien, et al. "Resveratrol inhibits HCoV-229E and SARS-CoV-2 coronavirus replication in vitro." Viruses 13.2 (2021): 354.

Spermidine

Spermidine is an endogenously produced polyanion [13], which can upregulate levels of autophagy [14,15]. Autophagy is a potential treatment strategy for Covid-19 [16], and can clear the spike protein [17]. 

[13] Madeo, Frank, et al. "Spermidine in health and disease." Science 359.6374 (2018): eaan2788.

[14] Madeo, Frank, et al. "Spermidine: a novel autophagy inducer and longevity elixir." Autophagy 6.1 (2010): 160-162.

[15] Eisenberg, Tobias, et al. "Induction of autophagy by spermidine promotes longevity." Nature cell biology 11.11 (2009): 1305-1314.

[16] Pereira, Gustavo Jose da Silva, et al. "Pharmacological Modulators of Autophagy as a Potential Strategy for the Treatment of COVID-19." International Journal of Molecular Sciences 22.8 (2021): 4067.

[17] Randhawa, Puneet Kaur, et al. "Modulation of autophagy by SARS-CoV-2: a potential threat for cardiovascular system." Frontiers in Physiology 11 (2020): 611275.

Mealtime Formula

Our mealtime formula contains ingredients which are associated with greater energy production. Long covid and vaccine injury are characterized by a persistent brain fog. One possible mechanism of brain fog is spike protein induced mitochondrial dysfunction, and another mechanism is inhibition of tissue oxygenation by microclots[1]. 

Calcium Ascorbate (Vitamin C)

Vitamin C can help with post viral fatigue, as supplementation is associated with a reduction in post viral fatigue [2], as well as an improvement in general fatigue when combined with l-arginine [3]. Another study demonstrated improved oxygenation, a decrease in inflammatory markers, and a faster recovery in initial COVID-19 infection [4]. Vitamin C is also associated with better long covid outcomes[5].

Vitamin D3

Vitamin D levels in serum are highly associated with recovery outcomes in acute Covid-19[6]. It is also examined as a therapeutic in long covid [7].

Vitamin K2

Vitamin K2 levels are depleted in Covid-19 infection and K2 levels are negatively associated with the severity of Covid-19 infection [8].

Nattokinase

Nattokinase, a fibrinolytic enzyme naturally occurring in fermented soybeans produced by the bacterial species Bacillus subtilis var. natto, proves valuable in dissolving blood clots[9], [10]. Research has shown its impressive ability to break down the spike protein[11], offering an additional advantage alongside its fibrinolytic and anti-coagulant characteristics[12]. Additionally, nattokinase has anti-SARS-CoV-2 impacts in cell culture [13]

N-acetyl Cysteine (NAC)

N-acetyl cysteine potentially acts on spike protein associated pathologies through its antioxidant, anti-inflammatory and cellular metabolism modulating properties[14]–[16], [16], [17], as well as possibly perturbing the interaction between spike protein and ACE2 receptors [18].

Pyrroloquinoline Quinone (PQQ)

Pyrroloquinoline Quinone (PQQ) plays important roles in biological processes including mitochondrial biogenesis[19], [20]. As spike protein can damage mitochondria[21]–[23], improving mitochondrial turnover is a possible means of restoring mitochondrial energy production[1].

[1]         M. T. J. Halma, P. E. Marik, and Y. M. Saleeby, ‘Exploring Autophagy in Treating Spike Protein-related Pathology’. Preprints, Jun. 27, 2023. doi: 10.20944/preprints202306.1903.v1.

[2]         C. Vollbracht and K. Kraft, ‘Feasibility of Vitamin C in the Treatment of Post Viral Fatigue with Focus on Long COVID, Based on a Systematic Review of IV Vitamin C on Fatigue’, Nutrients, vol. 13, no. 4, Art. no. 4, Apr. 2021, doi: 10.3390/nu13041154.

[3]         M. Tosato et al., ‘Effects of l-Arginine Plus Vitamin C Supplementation on Physical Performance, Endothelial Function, and Persistent Fatigue in Adults with Long COVID: A Single-Blind Randomized Controlled Trial’, Nutrients, vol. 14, no. 23, p. 4984, Nov. 2022, doi: 10.3390/nu14234984.

[4]         C. Vollbracht and K. Kraft, ‘Oxidative Stress and Hyper-Inflammation as Major Drivers of Severe COVID-19 and Long COVID: Implications for the Benefit of High-Dose Intravenous Vitamin C’, Front Pharmacol, vol. 13, p. 899198, 2022, doi: 10.3389/fphar.2022.899198.

[5]         R. Izzo et al., ‘Combining L-Arginine with vitamin C improves long-COVID symptoms: The LINCOLN Survey’, Pharmacol Res, vol. 183, p. 106360, Sep. 2022, doi: 10.1016/j.phrs.2022.106360.

[6]         M. S. Gönen et al., ‘Rapid and Effective Vitamin D Supplementation May Present Better Clinical Outcomes in COVID-19 (SARS-CoV-2) Patients by Altering Serum INOS1, IL1B, IFNg, Cathelicidin-LL37, and ICAM1’, Nutrients, vol. 13, no. 11, Art. no. 11, Nov. 2021, doi: 10.3390/nu13114047.

[7]         L. Barrea et al., ‘Vitamin D: A Role Also in Long COVID-19?’, Nutrients, vol. 14, no. 8, p. 1625, Apr. 2022, doi: 10.3390/nu14081625.

[8]         H. Mangge et al., ‘Dramatic Decrease of Vitamin K2 Subtype Menaquinone-7 in COVID-19 Patients’, Antioxidants (Basel), vol. 11, no. 7, p. 1235, Jun. 2022, doi: 10.3390/antiox11071235.

[9]         M. Fujita, K. Nomura, K. Hong, Y. Ito, A. Asada, and S. Nishimuro, ‘Purification and Characterization of a Strong Fibrinolytic Enzyme (Nattokinase) in the Vegetable Cheese Natto, a Popular Soybean Fermented Food in Japan’, Biochemical and Biophysical Research Communications, vol. 197, no. 3, pp. 1340–1347, Dec. 1993, doi: 10.1006/bbrc.1993.2624.

[10]      E. Pais, T. Alexy, J. Holsworth, and H. J. Meiselman, ‘Effects of nattokinase, a pro-fibrinolytic enzyme, on red blood cell aggregation and whole blood viscosity’, Clinical Hemorheology and Microcirculation, vol. 35, no. 1–2, pp. 139–142, Jan. 2006, Accessed: Apr. 08, 2023. [Online]. Available: https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch914

[11]      T. Tanikawa et al., ‘Degradative Effect of Nattokinase on Spike Protein of SARS-CoV-2’, Molecules, vol. 27, no. 17, p. 5405, Aug. 2022, doi: 10.3390/molecules27175405.

[12]      R.-L. Hsu, K.-T. Lee, J.-H. Wang, L. Y.-L. Lee, and R. P.-Y. Chen, ‘Amyloid-Degrading Ability of Nattokinase from Bacillus subtilis Natto’, J. Agric. Food Chem., vol. 57, no. 2, pp. 503–508, Jan. 2009, doi: 10.1021/jf803072r.

[13]      M. Oba et al., ‘Natto extract, a Japanese fermented soybean food, directly inhibits viral infections including SARS-CoV-2 in vitro’, Biochemical and Biophysical Research Communications, vol. 570, pp. 21–25, Sep. 2021, doi: 10.1016/j.bbrc.2021.07.034.

[14]      F. L. Poe and J. Corn, ‘N-Acetylcysteine: A potential therapeutic agent for SARS-CoV-2’, Med Hypotheses, vol. 143, p. 109862, Oct. 2020, doi: 10.1016/j.mehy.2020.109862.

[15]      P. Sengupta and S. Dutta, ‘N-acetyl cysteine as a potential regulator of SARS-CoV-2-induced male reproductive disruptions’, Middle East Fertil Soc J, vol. 27, no. 1, p. 14, 2022, doi: 10.1186/s43043-022-00104-8.

[16]      Z. Shi and C. A. Puyo, ‘N-Acetylcysteine to Combat COVID-19: An Evidence Review’, Ther Clin Risk Manag, vol. 16, pp. 1047–1055, Nov. 2020, doi: 10.2147/TCRM.S273700.

[17]      K. K. Wong, S. W. H. Lee, and K. P. Kua, ‘N-Acetylcysteine as Adjuvant Therapy for COVID-19 – A Perspective on the Current State of the Evidence’, J Inflamm Res, vol. 14, pp. 2993–3013, Jul. 2021, doi: 10.2147/JIR.S306849.

[18]      U. Debnath, V. Dewaker, Y. S. Prabhakar, P. Bhattacharyya, and A. Mandal, ‘Conformational Perturbation of SARS-CoV-2 Spike Protein Using N-Acetyl Cysteine, a Molecular Scissor: A Probable Strategy to Combat COVID-19’. ChemRxiv, Jan. 05, 2021. doi: 10.26434/chemrxiv.12687923.v1.

[19]      P. S. Hwang et al., ‘Effects of Pyrroloquinoline Quinone (PQQ) Supplementation on Aerobic Exercise Performance and Indices of Mitochondrial Biogenesis in Untrained Men’, Journal of the American College of Nutrition, vol. 39, no. 6, pp. 547–556, Aug. 2020, doi: 10.1080/07315724.2019.1705203.

[20]      K. R. Jonscher, W. Chowanadisai, and R. B. Rucker, ‘Pyrroloquinoline-Quinone Is More Than an Antioxidant: A Vitamin-like Accessory Factor Important in Health and Disease Prevention’, Biomolecules, vol. 11, no. 10, p. 1441, Sep. 2021, doi: 10.3390/biom11101441.

[21]      E. Clough et al., ‘Mitochondrial Dynamics in SARS-COV2 Spike Protein Treated Human Microglia: Implications for Neuro-COVID’, J Neuroimmune Pharmacol, vol. 16, no. 4, pp. 770–784, Dec. 2021, doi: 10.1007/s11481-021-10015-6.

[22]      T. V. Huynh, L. Rethi, T.-W. Lee, S. Higa, Y.-H. Kao, and Y.-J. Chen, ‘Spike Protein Impairs Mitochondrial Function in Human Cardiomyocytes: Mechanisms Underlying Cardiac Injury in COVID-19’, Cells, vol. 12, no. 6, p. 877, Mar. 2023, doi: 10.3390/cells12060877.

[23]      E. S. Kim, M.-T. Jeon, K.-S. Kim, S. Lee, S. Kim, and D.-G. Kim, ‘Spike Proteins of SARS-CoV-2 Induce Pathological Changes in Molecular Delivery and Metabolic Function in the Brain Endothelial Cells’, Viruses, vol. 13, no. 10, p. 2021, Oct. 2021, doi: 10.3390/v13102021.

Nighttime Formula

Restful sleep is extremely important for recovery from long covid, and long covid can impact sleep quality[1]. Our nighttime formula is designed to improve sleep as well as improving mitochondrial energy production.

Magnesium bis-glycinate

Magnesium is included in our nighttime formula because it is associated with more restful sleep[2], [3].

Melatonin

Melatonin is an important agent for sleep, and also has independent positive impacts on mitochondrial energy production by increasing mitophagy (autophagy of mitochondria) [4], [4], [5]and mitochondrial biogenesis[5]–[7]. The combination of the two can recycle damaged mitochondria.

[1]         C. Fernández-de-las-Peñas, J. D. Martín-Guerrero, I. Cancela-Cilleruelo, P. Moro-López-Menchero, J. Rodríguez-Jiménez, and O. J. Pellicer-Valero, ‘Trajectory curves of post-COVID anxiety/depressive symptoms and sleep quality in previously hospitalized COVID-19 survivors: the LONG-COVID-EXP-CM multicenter study’, Psychological Medicine, vol. 53, no. 9, pp. 4298–4299, Jul. 2023, doi: 10.1017/S003329172200006X.

[2]         A. Arab, N. Rafie, R. Amani, and F. Shirani, ‘The Role of Magnesium in Sleep Health: a Systematic Review of Available Literature’, Biol Trace Elem Res, vol. 201, no. 1, pp. 121–128, Jan. 2023, doi: 10.1007/s12011-022-03162-1.

[3]         Y. Zhang et al., ‘Association of magnesium intake with sleep duration and sleep quality: findings from the CARDIA study’, Sleep, vol. 45, no. 4, p. zsab276, Apr. 2022, doi: 10.1093/sleep/zsab276.

[4]         C. Chen et al., ‘Melatonin ameliorates cognitive deficits through improving mitophagy in a mouse model of Alzheimer’s disease’, J Pineal Res, vol. 71, no. 4, p. e12774, Dec. 2021, doi: 10.1111/jpi.12774.

[5]         J.-W. Kang, J.-M. Hong, and S.-M. Lee, ‘Melatonin enhances mitophagy and mitochondrial biogenesis in rats with carbon tetrachloride-induced liver fibrosis’, Journal of Pineal Research, vol. 60, no. 4, pp. 383–393, 2016, doi: 10.1111/jpi.12319.

[6]         H. Kato et al., ‘Melatonin promotes adipogenesis and mitochondrial biogenesis in 3T3-L1 preadipocytes’, Journal of Pineal Research, vol. 59, no. 2, pp. 267–275, 2015, doi: 10.1111/jpi.12259.

[7]         Y.-J. Niu, W. Zhou, Z.-W. Nie, K.-T. Shin, and X.-S. Cui, ‘Melatonin enhances mitochondrial biogenesis and protects against rotenone-induced mitochondrial deficiency in early porcine embryos’, Journal of Pineal Research, vol. 68, no. 2, p. e12627, 2020, doi: 10.1111/jpi.12627.