Our Science · Ingredients

Every Ingredient Earns 
its place : what does the 
science show?

By a specific, published mechanism of action.

Our Science · Ingredients

Every Ingredient Earns 
its place : what does the 
science show?

By a specific, published mechanism of action.

Our Science · Ingredients

Every Ingredient Earns 
its place : what does the 
science show?

By a specific, published mechanism of action.

"

These are not marketing promises.
They are operating principles.

Every formulation decision, every line of copy, and every label disclosure is measured against these four commitments —
because aging well deserves a brand that tells the truth about what it's selling.

Title

THE MORNING CASE

The evidence behind each

  • Spermidine

  • L-Theanine

  • Saffron

  • NMN

  • Urolithin A

  • CoQ10

  • TMG

  • PQQ

  • Trans-Resveratrol

  • Apigenin

  • Magnesium Glycinate

CALM · Cellular Recycling Research

Spermidine

 A naturally occurring polyamine, studied for cellular recycling.

Spermidine is a polyamine found in the body and in foods. It is studied for its relationship with autophagy, the process cells use to break down and reuse worn or damaged components. This research connects spermidine with cellular maintenance, but a biological role is not the same as a proven supplement benefit. Spermidine is the planned hero ingredient in CALM. [1,3]

RESEARCH EVIDENCE

Foundational research linked spermidine with autophagy and lifespan in yeast, flies, worms, and cultured cells, not clinical human longevity. [1] In a later randomized, placebo-controlled trial, a spermidine-rich wheat-germ extract did not improve the primary memory outcome over a year in older adults with subjective cognitive decline. [3] These findings do not establish improved sleep, longer human lifespan, or benefits of the finished CALM formula.

MECHANISM

Laboratory experiments linked spermidine-induced autophagy with inhibition of EP300, an enzyme involved in regulating protein acetylation and autophagy. This offers a possible route to cellular recycling; it does not establish that an oral supplement activates the same process in people. [2]

Title

SELECTED REFERENCES

1   Eisenberg T et al. (2009). Induction of autophagy by spermidine promotes longevity. Nature Cell Biology.  DOI: 10.1038/ncb1975
2   Pietrocola F et al. (2015). Spermidine induces autophagy by inhibiting the acetyltransferase EP300. Cell Death & Differentiation. DOI: 10.1038/cdd.2014.215
3   Schwarz C et al. (2022). Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial. JAMA Network Open.    DOI: 10.1001/jamanetworkopen.2022.13875

These are not studies of the finished CALM formula. Findings from ingredient studies do not establish the benefits or safety of the finished RESETTA formulas.

† These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

CALM ·Relaxation & Sleep Research

L-Theanine

An amino acid found in tea, studied for relaxation and sleep.

L-Theanine is an amino acid naturally found in tea leaves. It is studied in relation to relaxation, stress-related symptoms, and sleep quality, and is part of the developing CALM formula. Research on L-theanine alone should be distinguished from studies that combine it with caffeine, other nutrients, or botanical extracts. Its presence in tea does not establish how a finished supplement will perform. [1,2]

RESEARCH EVIDENCE

A systematic review found improvements in some subjective sleep outcomes, but limited research on pure L-theanine restricts conclusions about the ingredient alone. [2] A small trial in healthy adults found improvements in selected sleep subscales, but not the overall sleep score versus placebo. [1] In an add-on trial in generalized anxiety disorder, L-theanine did not outperform placebo for anxiety or overall insomnia severity. [3] The findings do not establish treatment of anxiety or insomnia, or the effects of CALM.

MECHANISM

L-Theanine is structurally similar to glutamate. Laboratory and animal research has explored effects on glutamate-related signaling and other neurotransmitter systems. These proposed pathways help explain interest in relaxation, but the human trials do not establish that these mechanisms cause a sleep benefit in people. [1]

Title

SELECTED REFERENCES

1   Hidese S et al. (2019). Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial. Nutrients.  DOI: 10.3390/nu11102362
2   Bulman et al. (2025). The effects of L-theanine consumption on sleep outcomes: A systematic review and meta-analysis. Sleep Medicine Reviews.  DOI: 10.1016/j.smrv.2025.102076
3   Sarris J et al. (2019). L-theanine in the adjunctive treatment of generalized anxiety disorder: A double-blind, randomised, placebo-controlled trial. Journal of Psychiatric Research. DOI: 10.1016/j.jpsychires.2018.12.014

These are not studies of the finished CALM formula. Findings from ingredient studies do not establish the benefits or safety of the finished RESETTA formulas.

† These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

CALM ·Sleep & Mood Research

Saffron

A botanical studied for sleep quality and emotional well-being.

Saffron comes from the stigmas of Crocus sativus. Its constituents include crocins and safranal, which are being investigated in relation to mood and sleep. Research uses defined extracts, not a single interchangeable form of saffron: extraction methods and standardization can change the ingredient profile. Saffron is part of the developing CALM formula, whose final extract specification must be assessed separately. [1,3]

RESEARCH EVIDENCE

Short randomized, placebo-controlled studies of the standardized extract affron reported improvements in selected self-reported sleep measures in adults with poor sleep; not every sleep measure improved. [1,2] In a separate trial using Safr'Inside, the primary overall mood outcome did not improve, although some secondary measures did. [3] These findings are extract-specific and short-term. They do not establish that saffron or CALM treats insomnia or depression, or that another extract will produce the same results.

MECHANISM

Proposed pathways include effects of saffron constituents on neurotransmitter signaling and oxidative-stress processes, largely from preclinical research. A human sleep trial also observed changes in evening melatonin, but this does not establish a causal mechanism for better sleep. The pathways, clinical outcomes, and finished CALM formula must be evaluated separately. [1,2]

Title

SELECTED REFERENCES

1   Lopresti AL et al. (2020). Effects of saffron on sleep quality in healthy adults with self-reported poor sleep: a randomized, double-blind, placebo-controlled trial. Journal of Clinical Sleep Medicine.  DOI: 10.5664/jcsm.8376
2   Lopresti AL et al. (2021). An investigation into an evening intake of a saffron extract (affron) on sleep quality, cortisol, and melatonin concentrations in adults with poor sleep: a randomised, double-blind, placebo-controlled, multi-dose study. Sleep Medicine.  DOI: 10.1016/j.sleep.2021.08.001
3   Jackson PA et al. (2021). Effects of Saffron Extract Supplementation on Mood, Well-Being, and Response to a Psychosocial Stressor in Healthy Adults: A Randomized, Double-Blind, Parallel Group, Clinical Trial. Frontiers in Nutrition. DOI: 10.3389/fnut.2020.606124

These are not studies of the finished CALM formula. Findings from ingredient studies do not establish the benefits or safety of the finished RESETTA formulas.

† These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

CORE · NAD⁺ Precursor

NMN

A direct precursor to cellular energy, one step closer than earlier forms.

NAD⁺ is a coenzyme behind more than 500 enzymatic processes — including mitochondrial energy metabolism and the activation of sirtuin proteins. 
Research indicates NAD⁺ levels tend to decline with age. NMN sits one metabolic step closer to NAD⁺ than earlier precursor forms, converting through established cellular pathways.†

RESEARCH EVIDENCE

Multiple randomized, placebo-controlled human trials have evaluated oral NMN supplementation and found it to be safe and well-tolerated, with associations including increased NAD⁺ levels in blood. A dose-dependent multicenter trial reported blood NAD⁺ increases with oral dosing evaluated up to 900 mg daily, alongside patient-reported and physical-performance measures. Additional trials in older adults have associated 250 mg/day with higher blood NAD⁺ and measures such as walking speed. Individual results may vary.†

References— Front. Nutrition, 2022 · Sci. Reports, 2023 · Endocrine J., 2020

MECHANISM

NMN → NAD⁺ via NMNAT enzymes → supports sirtuin activation, PARP-related DNA maintenance, and mitochondrial energy metabolism.

These are not studies of the finished CALM formula. Findings from ingredient studies do not establish the benefits or safety of the finished RESETTA formulas.

† These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

CORE · Mitophagy Support

Urolithin A

Supporting Mitochondrial Quality Control Through Mitophagy

NMN supports NAD⁺ levels. CoQ10 supports mitochondrial efficiency. PQQ supports the creation of new mitochondria. Urolithin A contributes a complementary dimension: it supports the selective clearance of damaged mitochondria through a process called mitophagy — the cell's quality-control mechanism. Research suggests that when damaged mitochondria accumulate faster than they are cleared, the net efficiency of the mitochondrial network is reduced.†

RESEARCH EVIDENCE

Peer-reviewed studies — including a first-in-human randomized controlled trial (2019) — have shown that oral Urolithin A is safe, well-tolerated, and associated with mitophagy-related gene expression in skeletal muscle. Subsequent randomized trials have reported associations with muscle endurance and mitochondrial health markers. Studies suggest approximately 60% of adults may not efficiently convert dietary ellagitannins to Urolithin A through gut metabolism alone.†

References — Nature Metabolism, 2019 · JAMA Network Open, 2022 · Cell Reports Medicine, 2022

MECHANISM

Mitophagy pathway activation (LC3/Pink1-Parkin) → selective clearance of dysfunctional mitochondria → improved net mitochondrial network quality

These are not studies of the finished CALM formula. Findings from ingredient studies do not establish the benefits or safety of the finished RESETTA formulas.

† These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

CORE · Mitochondrial Energy

CoQ10 

Supporting the Mitochondrial Energy Production Chain.

Coenzyme Q10 is a naturally occurring lipid-soluble compound found in every cell, with the highest concentrations in the inner mitochondrial membrane. It functions as an electron carrier within the electron transport chain, helping to generate ATP — the primary form of cellular energy. CoQ10 levels are known to decline with age. It also functions as a lipid-soluble antioxidant, supporting cell membrane integrity in environments where water-soluble antioxidants cannot reach.†

RESEARCH EVIDENCE

Peer-reviewed research has evaluated CoQ10 supplementation in various populations. Studies have reported associations with mitochondrial energy markers, antioxidant activity, and exercise-related outcomes. Individual results may vary.†

References— Frontiers in Physiology, 2018

MECHANISM

Electron transfer between Complex I and Complex III → proton gradient support → ATP synthesis facilitation · lipid-soluble antioxidant activity in mitochondrial and cellular membranes

These are not studies of the finished CALM formula. Findings from ingredient studies do not establish the benefits or safety of the finished RESETTA formulas.

† These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

CORE · Methylation Support

TMG

Supporting the Methylation Cycle.

NAD⁺ metabolism produces nicotinamide (NAM) as a byproduct, which the body processes through methylation pathways. TMG (trimethylglycine, also known as betaine) is a methyl donor that supports the methylation cycle, including the remethylation of homocysteine to methionine. Including TMG supports the broader metabolic environment in which sustained NAD⁺ support occurs.†

RESEARCH EVIDENCE

Betaine supplementation has been associated with homocysteine levels and methylation cycle markers in peer-reviewed studies. Individual results may vary.†

References— Journal of Nutrition, 2003

MECHANISM

Methyl group donation via the BHMT pathway → supports the methionine–SAM cycle

These are not studies of the finished CALM formula. Findings from ingredient studies do not establish the benefits or safety of the finished RESETTA formulas.

† These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

CLARITY · Mitochondrial Biogenesis

PQQ

Supporting the Creation of New Mitochondria.

PQQ is a redox-active compound found in trace amounts in many foods. It has been studied for its potential role in supporting mitochondrial biogenesis — the process by which cells generate new mitochondria. Research suggests PQQ may activate PGC-1α, a regulatory protein involved in mitochondrial production. As a catalytic redox cofactor, PQQ can participate in multiple redox cycles, supporting antioxidant activity within mitochondria.†

RESEARCH EVIDENCE

Human research has associated PQQ supplementation with cognitive performance outcomes including memory and attention measures. Preclinical studies suggest neuroprotective activity and effects on nerve growth factor (NGF). Research is ongoing and individual results may vary.†

References— Journal of Biological Chemistry, 2010 · Advances in Experimental Medicine and Biology, 2016

MECHANISM

PGC-1α pathway support → mitochondrial biogenesis signaling → antioxidant activity via catalytic redox cycling.

These are not studies of the finished CALM formula. Findings from ingredient studies do not establish the benefits or safety of the finished RESETTA formulas.

† These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

CLARITY · Sirtuin Pathway Support

Trans-Resveratrol

Supporting the Sirtuin Signaling Pathway.

Trans-resveratrol is the biologically active form of resveratrol, a polyphenol found in grapes and other plants. It has been studied for its potential interactions with sirtuin proteins — a family of enzymes involved in cellular maintenance processes that require NAD⁺. Research has explored resveratrol's potential to support SIRT1 activity and pathways that overlap with those associated with caloric restriction in preclinical models. Trans-resveratrol is used in RESETTA because research suggests this stereoisomeric form has greater activity in relevant pathways compared to cis-resveratrol.†

RESEARCH EVIDENCE

Human research has associated resveratrol supplementation with mitochondrial function markers, antioxidant activity, and inflammatory marker outcomes. Findings vary across studies and individual results may differ. Resveratrol has low oral bioavailability as a standalone compound; absorption is supported by co-administration with piperine.†

References— Cell Metabolism, 2011 · Molecular Nutrition & Food Research, 2011

MECHANISM

Polyphenol-mediated sirtuin pathway support · AMPK pathway associations · antioxidant and anti-inflammatory activity.

These are not studies of the finished CALM formula. Findings from ingredient studies do not establish the benefits or safety of the finished RESETTA formulas.

† These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

CALM· Relaxation Support

Apigenin

Supporting the Body's Natural Wind-Down Response.

Apigenin is a flavonoid found in chamomile and other plants, studied for its interaction with receptors involved in the body's calming response. Research suggests apigenin may act on the same receptor site as compounds associated with relaxation, without the dependency profile of pharmaceutical options.†

RESEARCH EVIDENCE

Human research on chamomile extract (containing apigenin) has associated supplementation with improved subjective sleep quality measures. Preclinical studies suggest apigenin binds the benzodiazepine site of the GABA-A receptor. Individual results may vary.†

References— BMC Complementary and Alternative Medicine, 2011 · Planta Medica, 1995

MECHANISM

GABA-A receptor (benzodiazepine site) interaction → supports nervous system relaxation signaling.

These are not studies of the finished CALM formula. Findings from ingredient studies do not establish the benefits or safety of the finished RESETTA formulas.

† These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

CALM · Muscle & Sleep Support

Magnesium Glycinate

Supporting Muscle Relaxation and Sleep Onset.

Magnesium is a cofactor in more than 300 enzymatic reactions, including those involved in nervous system regulation and muscle function. Magnesium glycinate pairs magnesium with glycine, an amino acid also studied for its own calming properties, in a form chosen for gentle digestibility.†

RESEARCH EVIDENCE

Research has associated magnesium supplementation with sleep quality measures in older adults, and separately, glycine ingestion with improved subjective sleep quality. Individual results may vary.†

References— Journal of Research in Medical Sciences, 2012 · Sleep and Biological Rhythms, 2007

MECHANISM

NMDA receptor modulation and GABA pathway support → muscle relaxation · glycine co-action on sleep architecture.

These are not studies of the finished CALM formula. Findings from ingredient studies do not establish the benefits or safety of the finished RESETTA formulas.

† These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.