Protocol FAQ

A supplement is a single product taken without a defined goal or duration. A protocol is a structured approach: a specific product or combination, taken at a specific dose, at a specific time, for a defined period, with a defined outcome you're measuring. The clinical literature our formulas are based on used protocols — not ad hoc supplementation. Matching that rigor is how you replicate the results. A protocol has a start date, a minimum duration (usually 8–12 weeks), a measurement method (bloodwork, wearable data, or subjective tracking), and a decision point at the end: continue, adjust, or rotate.

Minimum 8 weeks for subjective markers (energy, sleep, mood, cognitive clarity). Minimum 12 weeks for objective biomarker changes visible on bloodwork. Some outcomes — biological age markers, HRV trends, body composition — require 16–24 weeks of consistent use to show statistically meaningful change.

The biggest mistake is quitting at week 3 because "you don't feel anything." Most meaningful physiological changes — NAD+ upregulation, mitochondrial biogenesis, BDNF expression — are not perceptible to conscious awareness. They show in data before they show in feeling.

Yes — strongly recommended. Without a baseline you have no way to quantify whether the protocol is working. A baseline panel is especially important if you're using Immortalis (NAD+ precursors, biological age markers), GutShield Pro (inflammatory markers, gut permeability markers), or Cycle Balance (hormone panel). At minimum, get: CBC, metabolic panel, hsCRP, fasting insulin, and — depending on your protocol — NAD+ levels, hormone panel, or lipid panel. Retest at 12 weeks. Services like Function Health, InsideTracker, or your primary care physician can run these.

If you're new to high-quality supplementation, introduce one product at a time with a 1–2 week gap before adding the next. This serves two purposes: it lets you isolate which product is driving any effect (positive or negative), and it reduces the cognitive load of managing a complex protocol from day one. If you're experienced and have no known sensitivities, starting two complementary products simultaneously (e.g., Immortalis + Neural Stack) is fine — they don't share overlapping actives at meaningful doses.

For most supplements, consistency of timing matters more than the specific time. That said, some ingredients have pharmacokinetic reasons for specific timing windows:

Each product page includes a recommended timing note. If in doubt: fat-soluble ingredients with food, adaptogens in the evening, stimulatory nootropics in the morning.

Fat-soluble actives require food with dietary fat: CoQ10, phosphatidylserine, curcumin, omega-3s, and fat-soluble vitamins (A, D, E, K) all depend on bile acid secretion for absorption — which food triggers. Taking these fasted can reduce bioavailability by 30–60%. Water-soluble actives can be taken fasted: NMN, vitamin C, B-vitamins, L-theanine, and most amino acids absorb well without food. Berberine is the exception: take it 15–30 minutes before meals to exploit its glucose transporter activation effect during the post-meal glycemic window.

For ingredients with short plasma half-lives — berberine (t½ ≈ 3h), vitamin C (t½ ≈ 2h), resveratrol (t½ ≈ 1.5h) — splitting the daily dose into two or three smaller doses maintains more consistent plasma concentrations than a single large dose. For longer-acting compounds — ashwagandha (effects persist 8–12h), NMN (converted to NAD+ which has a longer biological half-life), phosphatidylserine — once-daily dosing is adequate. Our products are formulated with this in mind; the label dose is optimized for single daily administration unless otherwise noted.

IF is compatible with most of our protocols. The practical approach: take water-soluble actives (NMN, B-vitamins, L-theanine, magnesium) during your fasted window without issue. Delay fat-soluble actives (CoQ10, curcumin, PS, vitamin D) until your first meal of the eating window. Berberine should be taken around meals as designed.

Both NMN and NR are NAD+ precursors — they both ultimately raise intracellular NAD+ levels. The key difference is the conversion pathway: NR converts to NMN before becoming NAD+, meaning NMN is one step closer to the final product. More importantly, NMN has its own transporter (Slc12a8) that allows direct cellular uptake in some tissues, which NR lacks. Human trials from the Yoshino lab (Wash U) have shown NMN raises blood NAD+ levels within 30 minutes at a 250mg dose. We use β-NMN (the biologically active stereoisomer) sourced from Uthever® — one of the few suppliers with human pharmacokinetic data on their specific form.

The comparison is mechanistically grounded. Both berberine and metformin activate AMPK (AMP-activated protein kinase), which improves insulin sensitivity, inhibits hepatic glucose production, and activates autophagy pathways. A 2008 meta-analysis in Metabolism found berberine at 500mg three times daily produced equivalent HbA1c and fasting glucose reductions to metformin in type 2 diabetic patients over 3 months.

The differences: metformin also inhibits mitochondrial complex I and has stronger evidence for long-term outcomes. Berberine has additional mechanisms — it modulates gut microbiome composition and upregulates GLP-1 secretion — which metformin doesn't share to the same degree. The two should not be combined without physician oversight due to additive glucose-lowering risk.

Lion's Mane (Hericium erinaceus) contains two classes of active compounds — hericenones (in the fruiting body) and erinacines (in the mycelium) — that stimulate nerve growth factor (NGF) synthesis. NGF is critical for the maintenance and survival of neurons, and declining NGF production is associated with age-related cognitive decline. The key RCT (Mori et al., 2009) used 1,000mg of dried fruiting body three times daily (3,000mg total) and showed statistically significant improvements on cognitive function scales over 16 weeks. Dose is everything here: most Lion's Mane supplements on the market contain 300–500mg — below the threshold used in the study we cite. We use 1,000mg of fruiting body extract standardized to ≥30% beta-glucans per serving of Neural Stack.

Methylene Blue (MB) is a phenothiazine compound with a unique mechanism: it acts as a mitochondrial electron carrier, accepting electrons from NADH and donating them to cytochrome c, effectively bypassing dysfunctional segments of the electron transport chain. This can enhance ATP production in cells with compromised mitochondria — which is why it's been studied in the context of cognitive aging and neurodegenerative conditions.

At low doses (0.5–4mg/kg), it has nootropic and neuroprotective effects. At higher doses it behaves differently and carries risk. Our formulations use pharmaceutical-grade USP-certified Methylene Blue only — contaminated sources (industrial grade) are dangerous and should never be ingested.

Generally don't require cycling: NMN, NAD+ precursors, magnesium, omega-3s, phosphatidylserine, CoQ10, B-vitamins, and most vitamins and minerals. These support baseline physiological function and there's no evidence of tolerance development or receptor downregulation with continuous use.

Often benefit from cycling: Adaptogens (ashwagandha, rhodiola, eleuthero) — a common practitioner protocol is 8–12 weeks on, 2–4 weeks off. The rationale is to prevent receptor desensitization and maintain HPA axis responsiveness. This is practitioner consensus rather than hard RCT data, but it's a reasonable precaution.

Individual variation matters: Some people run ashwagandha year-round without diminishing returns. Others notice reduced effect after 3–4 months. If you notice the effect fading, a 3–4 week break typically restores sensitivity.

The current evidence does not support mandatory cycling of NMN. The human trials have used continuous supplementation over 8–24 weeks without evidence of tolerance, receptor downregulation, or adverse adaptation. David Sinclair, whose lab pioneered much of the foundational NMN research, has publicly stated he takes NMN daily without cycling. That said, this is a relatively new compound in the human trial context and long-term data beyond 2 years is limited. As a precaution, some practitioners suggest a 1-week break every 3–4 months — this is conservative rather than evidence-based. We do not consider it necessary based on current literature.

A rotation means running one protocol for a defined period, assessing outcomes, then shifting focus. Example: 16 weeks on Immortalis (longevity focus) → get bloodwork → 12 weeks on HealForce (tissue repair, post-training) → get bloodwork → back to Immortalis. Immortalis stays as a continuous baseline; HealForce is layered on for specific training blocks. The key principle is that you're not randomly switching — you're making deliberate protocol decisions based on your current goal, training phase, or bloodwork findings. If you want a personalized rotation plan based on your health goals, email our clinical team at clinical@upgradehealth.com.

Core panel (all protocols): CBC, CMP, hsCRP, fasting insulin, fasting glucose, HbA1c, lipid panel, homocysteine.

Add for Immortalis / longevity protocols: NAD+ (plasma), GlycanAge or Dunedin PACE biological age test, IGF-1, DHEA-S, telomere length (optional, expensive).

Add for Cycle Balance / hormonal protocols: Full hormone panel (estrogen, progesterone, testosterone, SHBG, LH, FSH), DUTCH Complete (dried urine — preferred for sex hormone metabolites), thyroid panel (TSH, free T3, free T4).

Add for GutShield Pro: Zonulin, LPS (lipopolysaccharide), calprotectin, comprehensive stool analysis (Genova GI Effects or Vibrant Wellness GI-MAP).

A few possibilities. First: confirm your dose timing — NMN should be taken in the morning (fasted or with a light meal) to align with the natural circadian peak of NAD+ synthesis. Second: check for co-factor depletion. NMN → NAD+ conversion requires adequate levels of riboflavin (B2), niacin (B3), and magnesium. If any are deficient, the conversion bottleneck limits the NAD+ response. Third: consider PARP1 and CD38 hyperactivation — both are NAD+ consumers that are upregulated by chronic inflammation and oxidative stress. If your hsCRP is elevated, addressing the inflammatory driver may be necessary before NAD+ levels respond to supplementation. Email clinical@upgradehealth.com with your panel for a more specific assessment.

GlycanAge measures IgG glycosylation patterns — the ratio of pro-inflammatory to anti-inflammatory glycan modifications on antibodies. It correlates strongly with systemic inflammation and biological aging. A score lower than your chronological age is favorable. A 3–5 year improvement over a 6-month protocol is a meaningful signal; smaller changes (1–2 years) may be within measurement variability. Importantly, GlycanAge responds to lifestyle changes (diet, exercise, stress) as well as supplementation — isolating the protocol effect requires controlling those variables between tests. The Dunedin PACE clock (epigenetic) is more expensive but more mechanistically specific to aging rate if you want a second data point.

Well-validated combinations:

Use with more care: Combining Neural Stack with any other stimulatory cognitive product (e.g., racetams, high-dose caffeine stacks) may over-activate cholinergic pathways in sensitive individuals. Monitor for headache or overstimulation and reduce dose if needed. Cycle Balance should generally run as a standalone if you're also working with a clinician on hormone optimization — the interactions with exogenous hormones need professional oversight.

There's no universal limit, but practical logic applies: beyond 3–4 concurrent products, you lose the ability to isolate what's driving any given effect. If something goes wrong (unexpected side effect, bloodwork anomaly), you have no way to identify the cause. Our general guidance: run a core protocol of 1–2 products for 12 weeks, get bloodwork, then add a third if warranted by your data. The "more is more" instinct in supplementation is almost always wrong — synergy is real but so is interference, and the dose burden on your liver's metabolic pathways increases with each addition.

The interactions most relevant to our product range, in order of clinical significance:

Berberine + Metformin or GLP-1 agonists: Additive glucose-lowering. Can cause hypoglycemia. Requires physician monitoring.

Methylene Blue + Serotonergic medications: MB is a weak MAOI at low doses and a more potent one at higher doses. Combining with SSRIs, SNRIs, triptans, or tramadol risks serotonin syndrome. This is a hard contraindication — do not combine without specialist oversight.

Ashwagandha + Thyroid medication: Ashwagandha has documented thyroid-stimulating effects. If you're on levothyroxine or liothyronine, ashwagandha can alter dosing requirements. Monitor TSH at 8 weeks.

High-dose Omega-3 + Anticoagulants: Above 3g/day, omega-3s can potentiate warfarin and other blood thinners. At our standard doses this is generally not a concern, but warfarin patients should monitor INR more frequently when adding any omega-3 product.

We do not recommend any of our core protocol products during pregnancy or breastfeeding without explicit clearance from an OB-GYN or midwife. The clinical trials our formulas are based on excluded pregnant and breastfeeding participants, so the safety data simply doesn't exist for these populations. Ashwagandha in particular has uterine-stimulating properties documented in animal models and should be avoided entirely during pregnancy. If you are pregnant or planning to conceive, please consult your healthcare provider before starting or continuing any supplementation.

For most supplements, no. For a few, yes. NMN and exercise: There is animal data suggesting that NMN supplementation combined with aerobic exercise produces additive improvements in muscle NAD+ and mitochondrial density compared to either alone. Timing NMN 30–60 minutes before moderate aerobic exercise may exploit this synergy. Creatine (if applicable): Post-exercise timing shows a modest advantage in some studies. BPC-157 and collagen peptides (HealForce): Taking collagen with vitamin C in proximity to a training session has been shown to enhance collagen synthesis in tendons and connective tissue (Shaw et al., 2017) — the vitamin C is required for prolyl hydroxylase activity in collagen crosslinking.

In rough order of magnitude of impact: (1) Chronic sleep deprivation — below 7 hours consistently drives inflammation, accelerates epigenetic aging, and suppresses the growth hormone and testosterone secretion that many longevity protocols depend on. Supplements cannot outrun poor sleep. (2) Uncontrolled chronic stress — elevated cortisol suppresses DHEA, accelerates telomere attrition, and upregulates CD38 (an NAD+ consumer), directly undermining NAD+-focused protocols. (3) Ultra-processed food diet — drives systemic LPS translocation, neuroinflammation, and insulin resistance faster than most interventions can counteract. (4) Sedentary behavior — independent of weight, physical inactivity is one of the strongest predictors of biological aging rate. Our protocols are designed to compound with good health behaviors, not replace them.

Email our clinical support team at clinical@upgradehealth.com. Include: your current protocol (products + dose + timing), your health goals, any relevant bloodwork, and any medications or supplements you're taking. Our clinical team — which includes individuals with backgrounds in integrative medicine, pharmacology, and nutritional biochemistry — reviews every enquiry. We respond within 2 business days. We don't give medical diagnoses, but we can give rigorous, research-backed protocol guidance.