Once daily supplement: What the evidence shows

Tom
2026-04-27T23:01:47+01:00

A once daily supplement sounds simple. One dose, one moment in the day, done. But whether that format actually works depends entirely on what's in it, at what dose, and whether the evidence for single-daily dosing holds up under scrutiny. Some ingredients are genuinely well-suited to it. Others are being squeezed into a convenient format that doesn't match how the research was conducted.

In this article

1. What the evidence actually shows

2. What's biologically happening: absorption, half-lives, and saturation

3. Dosing: what the clinical evidence actually supports

4. Why format consistency matters more than people think

5. What to look for — and what to ignore — on the label

6. The polyphenol question: grape seed, pine bark, and olive leaf

7. Once-daily versus split dosing: does it actually matter?

8. Skin, collagen, and the once-daily format

9. Frequently asked questions

10. My honest take

What the evidence actually shows

Let me be direct about something first. Most of the clinical trials that inform supplement recommendations weren't designed around once-daily convenience. They were designed around efficacy. Sometimes the effective dosing schedule happened to be once daily. Sometimes it wasn't. The format question and the evidence question are not the same thing, and conflating them is where a lot of supplement marketing goes wrong.

That said, there is meaningful evidence for once-daily dosing in specific contexts. Grove-Laugesen et al. (2023) examined once-daily vitamin D supplementation in a randomised controlled trial — the DAGMAR trial — and found measurable effects on immune-related markers in participants with Graves' disease over 9 months. It's a specific population, so I wouldn't generalise wildly from it, but the once-daily protocol was the vehicle for a real, well-controlled study.

Naiyarakseree et al. (2023) used once-daily menaquinone-7 (vitamin K2) supplementation in a multicenter randomised trial of haemodialysis patients, finding that once-daily oral dosing was sufficient to achieve measurable changes in vascular markers over 12 weeks. Again — specific population, but the once-daily format was clinically validated, not just assumed.

And Garoufi et al. (2025) looked at a nutraceutical combination given once daily to children with elevated cholesterol, finding that the single-daily format produced measurable shifts in lipid profiles over 12 weeks. Sample size was modest (n=60), so I'd treat it as preliminary, but it's another data point for the once-daily model producing real outcomes.

The honest read: once-daily dosing works for some ingredients and some outcomes. It doesn't automatically work for everything. The format should follow the evidence, not the other way around.

What's biologically happening: absorption, half-lives, and saturation

The reason once-daily dosing is viable for some ingredients and not others comes down to pharmacokinetics — specifically, absorption rate, plasma half-life, and whether the relevant biological pool saturates gradually or requires a sustained presence.

Fat-soluble nutrients — vitamins D, K, A, E — are stored in adipose tissue and the liver. Their effective half-lives are measured in days or weeks. A single daily dose is more than sufficient to maintain circulating levels. There's no meaningful advantage to splitting the dose.

Water-soluble nutrients are different. Vitamin C, for instance, has a plasma half-life of roughly 10–20 minutes at high concentrations before renal clearance kicks in. The UK registered claim — that Vitamin C contributes to the protection of cells from oxidative stress — is supported by adequate daily intake, but the timing question is more nuanced. Splitting 500mg across two doses may maintain steadier plasma levels than a single 500mg hit, though for most people eating a reasonable diet, the practical difference is probably small.

Creatine is a useful case study. The body's creatine pool — primarily in skeletal muscle — saturates over approximately 28 days of consistent supplementation at 3–5g per day. Once saturated, timing matters very little. A single daily dose maintains that saturation as effectively as multiple smaller doses. That's why creatine is one of the ingredients genuinely well-suited to a once-daily format, and it's why the registered claim — that creatine increases physical performance in successive bursts of short-term, high intensity exercise — is achievable through once-daily supplementation once the loading period is complete.

Amino acids like glycine and taurine present a different picture. Both are conditionally synthesised endogenously, and their tissue concentrations respond to dietary and supplemental intake, but the precise kinetics in healthy adults aren't as well characterised as, say, creatine. Research on glycine and taurine is ongoing, and large-scale human trials establishing optimal dosing schedules are limited — so I'd be overstating it to tell you once-daily is definitively optimal for either.

Dosing: what the clinical evidence actually supports

This is where a lot of once-daily supplements fall apart. The format is convenient. The doses are often not.

Creatine monohydrate has been studied extensively. The maintenance dose supported by the literature is 3–5g per day. Mănescu et al. (2025) reviewed the mechanisms behind creatine's role in muscle physiology and noted that 5g daily is the most consistently studied maintenance dose in adult populations. The KōJō Daily Formula uses 5000mg of micronised creatine monohydrate — that's the upper end of the evidence-supported range, delivered in a single daily serving. No splitting required.

Vitamin C at 500mg daily is well above the UK RDA of 40mg, but within the range studied in clinical contexts. Vitamin C contributes to normal energy-yielding metabolism and to the reduction of tiredness and fatigue — both registered claims. The 500mg dose in a once-daily format is consistent with how these outcomes have been studied.

Rondanelli et al. (2022) reviewed supplementation strategies for bone mineral density, noting that consistent daily intake — rather than intermittent high-dose approaches — was associated with better outcomes across multiple nutrients. That's a useful general principle for once-daily supplement design: consistency matters more than timing precision for most ingredients.

For plant-derived extracts like aged garlic, olive leaf, grape seed, and pine bark — the human data on optimal dosing is genuinely thin. Studies exist, but they vary enormously in extract standardisation, dose, and duration. I'd be cautious about any brand claiming to have nailed the "optimal" dose for these. What I can say is that the doses used in KōJō's formula are within the ranges studied in the available literature. Research is ongoing, and large-scale human RCTs for each of these extracts are limited.

Why format consistency matters more than people think

There's a concept in adherence research sometimes called "dosing frequency burden." The simpler the regimen, the more likely someone is to follow it. Flaherman et al. (2024) studied once-daily small-volume formula supplementation in a breastfeeding context and found that the once-daily format was associated with higher adherence rates compared to more frequent dosing schedules. That's a very different context to adult supplementation, but the underlying principle — that fewer doses means fewer missed doses — is well established across pharmacological research.

This matters because the most effective supplement is the one you actually take. A formula that requires four separate doses throughout the day, each with specific food requirements, will be abandoned by most people within a few weeks. A well-designed once-daily format removes that friction entirely.

If you're looking at the broader category — powders, capsules, liquids — I've written more about the format question in my piece on daily vitamin powder, which gets into why powder format may offer absorption advantages over compressed tablets for certain ingredients.

What to look for — and what to ignore — on the label

A few things I check when evaluating a once-daily supplement:

Doses against the literature. Not against the RDA. Against what was actually used in clinical studies. These are often very different numbers.

Whether the once-daily format is justified by the ingredient's half-life. If an ingredient requires sustained plasma levels and has a short half-life, once-daily dosing may not be the right vehicle.

Transparency on extract standardisation. "Aged garlic extract 600mg" means nothing without knowing what it's standardised to. Same for olive leaf, grape seed, pine bark. The extract concentration determines the effective dose.

Registered claims versus marketing language. There's a meaningful difference between "Vitamin C contributes to normal collagen formation for the normal function of skin" — a registered, evidence-backed claim — and vague language about "supporting" or "nourishing." The former has a regulatory basis. The latter often doesn't.

What I tend to ignore: proprietary blends that obscure individual ingredient doses, anything described using superlatives without citations, and before/after imagery that has nothing to do with the ingredient's studied mechanism.

The polyphenol question: grape seed, pine bark, and olive leaf

These three ingredients appear in a growing number of once-daily formulas, and I want to be honest about where the evidence sits.

Grape seed extract, pine bark extract (standardised to oligomeric proanthocyanidins, or OPCs), and olive leaf extract (standardised to oleuropein) have all been studied for their antioxidant properties in vitro and in some human trials. Vitamin C contributes to the protection of cells from oxidative stress — that's a registered claim with a solid evidence base. The polyphenol extracts occupy a different category: the human data is more limited, study quality varies considerably, and I wouldn't make strong claims about what they do in a once-daily supplement format specifically.

What I can say is that research into these compounds is active and genuinely interesting. Large-scale, well-powered human RCTs are still limited for each of them individually. I include them in KōJō's formula because the preliminary data is promising and the safety profile at these doses is well-established — but I'm not going to overstate the efficacy evidence.

Similarly for taurine at 2000mg and glycine at 2000mg: both are conditionally essential amino acids with interesting mechanistic profiles, and both have been studied in various human contexts. But the evidence base for specific outcomes from supplementation in healthy adults is still developing. Research is ongoing, and I'd be doing you a disservice to claim otherwise.

Once-daily versus split dosing: does it actually matter?

For most of the ingredients in a well-designed once-daily formula, the honest answer is: probably not much, for most people.

Creatine: no meaningful difference once muscle stores are saturated. Verceles et al. (2023) reviewed protein and supplement strategies for muscle maintenance and noted that consistent daily intake — regardless of timing precision — was the primary driver of outcome in most studies.

Fat-soluble nutrients: once daily is genuinely optimal. Splitting the dose adds no benefit and creates unnecessary complexity.

Water-soluble nutrients at higher doses: there's a theoretical argument for split dosing to maintain steadier plasma levels. In practice, for someone eating a diet with any fruit or vegetables at all, the marginal benefit of splitting 500mg of vitamin C is likely small. I take it once daily and don't lose sleep over it.

The exception would be someone with a specific medical condition affecting absorption — but that's a conversation for a clinician, not a supplement journal entry. If you're exploring the broader energy and performance angle, my piece on energy supplement powder covers some of the timing nuances in more detail.

Skin, collagen, and the once-daily format

This is worth a brief section because it comes up a lot. Vitamin C contributes to normal collagen formation for the normal function of skin — that's a registered claim. The collagen synthesis pathway requires vitamin C as a cofactor for prolyl and lysyl hydroxylase enzymes. A daily dose is sufficient to support this pathway; you don't need to time it around meals in any specific way.

Proksch et al. (2014) found in a double-blind, placebo-controlled trial (n=69) that oral collagen peptide supplementation was associated with measurable changes in skin elasticity after 8 weeks, with effects persisting at 4 weeks post-supplementation. Kim et al. (2018) found similar signals in a randomised trial examining low-molecular-weight collagen peptides, with improvements in hydration and wrinkling scores over 12 weeks. Both studies used once-daily dosing protocols. Neither was enormous, and I'd call the evidence promising rather than definitive — but the once-daily format was the tested format.

KōJō's formula doesn't include collagen peptides, but the vitamin C at 500mg directly supports the endogenous collagen synthesis pathway. That's a more mechanistically direct approach than supplementing exogenous peptides, though both have their own evidence bases.

Frequently asked questions

Is once-daily dosing actually effective, or is it just convenient?

For many ingredients, once-daily dosing is both effective and convenient — but the two aren't always the same thing. Creatine, fat-soluble vitamins, and some plant extracts are well-suited to single daily doses based on their absorption profiles. The key is whether the dose matches what was studied in trials, as shown in Mănescu et al. (2025).

Does it matter what time of day I take a once-daily supplement?

For most ingredients, timing precision matters less than consistency. Fat-soluble nutrients may absorb slightly better with a meal containing some fat. Creatine timing has minimal impact once muscle stores are saturated, as noted in Verceles et al. (2023). Pick a time you'll remember and stick to it — that matters more than the clock.

Can a once-daily supplement replace a varied diet?

No, and I'd be sceptical of anyone suggesting otherwise. Supplements address specific gaps or provide specific ingredients at studied doses — they don't replicate the full matrix of whole foods. Rondanelli et al. (2022) makes this point clearly in the context of bone health: dietary patterns and supplementation work together, not interchangeably.

Why do some supplements recommend splitting the dose rather than taking it all at once?

Split dosing is sometimes recommended to maintain steadier plasma concentrations for ingredients with short half-lives, or to manage gastrointestinal tolerance at higher doses. For water-soluble nutrients at higher doses, there may be a modest absorption advantage to splitting. The human data on whether this produces meaningfully different outcomes in healthy adults is limited, as noted in Cohen et al. (2024).

How long does it take for a once-daily supplement to have any measurable effect?

It depends entirely on the ingredient and the outcome being measured. Creatine saturation takes approximately 28 days at maintenance doses. Skin-related outcomes in collagen studies typically showed measurable changes at 8–12 weeks, as in Kim et al. (2018). Lipid-related outcomes in Garoufi et al. (2025) appeared over 12 weeks. There are no meaningful overnight effects for any evidence-based supplement.

Are powder-based once-daily supplements better than capsules?

Powder format may offer advantages for ingredients like creatine, where a 5g dose would require roughly 10 large capsules. Absorption differences between powder and capsule for most ingredients are modest in healthy adults with normal gastric function. The practical advantage of powder is dose flexibility and the ability to include higher absolute doses without swallowing a handful of tablets.

My honest take

I built KōJō's formula around a once-daily format because I genuinely believe it's the right approach for the ingredients we've chosen — not because it's a convenient marketing angle. Creatine at 5g saturates muscle stores effectively with a single daily dose. Vitamin C at 500mg supports multiple registered physiological functions through once-daily intake. The plant extracts are at doses consistent with the available literature, even if that literature is thinner than I'd like.

What I'm less certain about: whether the precise combination of polyphenol extracts — grape seed, pine bark, olive leaf — produces additive effects in a once-daily format. The mechanistic rationale is plausible. The human trial data for these specific combinations is limited. I'm honest about that because I think you deserve to know where the evidence ends and the reasonable inference begins.

The once-daily format isn't a shortcut. Done properly, it reflects an honest accounting of each ingredient's pharmacokinetics and the dosing schedules used in the actual trials. Done lazily, it's just a marketing decision dressed up as science.

I've spent a lot of time in the primary literature on this. The conclusion I keep arriving at is that for a core set of well-studied ingredients — creatine, vitamin C, vitamin D, vitamin K2 — once-daily is genuinely appropriate. For the newer or less-studied ingredients, once-daily is probably fine, but I'd hold the efficacy claims more loosely until larger human trials emerge.

That's where I land. Take it for what it's worth.

This article is for informational purposes only and does not constitute medical advice. Consult your healthcare provider before starting any supplement regimen.

References (10 studies)

1. Proksch et al. (2014) — Oral supplementation of specific collagen peptides has beneficial effects on human skin physiology: a double-blind, placebo-controlled study. PMID 23949208.

2. Kim et al. (2018) — Oral Intake of Low-Molecular-Weight Collagen Peptide Improves Hydration, Elasticity, and Wrinkling in Human Skin: A Randomized, Double-Blind, Placebo-Controlled Study. PMID 29949889.

3. Cohen et al. (2024) — Nutritional Strategies for Managing Iron Deficiency in Adolescents: Approaches to a Challenging but Common Problem. PMID 38556251.

4. Mănescu et al. (2025) — Nutritional Supplements for Muscle Hypertrophy: Mechanisms and Morphology-Focused Evidence. PMID 41305653.

5. Rondanelli et al. (2022) — Nutrition, Physical Activity, and Dietary Supplementation to Prevent Bone Mineral Density Loss: A Food Pyramid. PMID 35010952.

6. Verceles et al. (2023) — Combining exercise, protein supplementation and electric stimulation to mitigate muscle wasting and improve outcomes. PMID 36473808.

7. Flaherman et al. (2024) — Breastfeeding and Once-Daily Small-Volume Formula Supplementation to Prevent Infant Growth Impairment. PMID 38062778.

8. Grove-Laugesen et al. (2023) — Effect of Vitamin D Supplementation on Graves' Disease: The DAGMAR Trial. PMID 37218433.

9. Garoufi et al. (2025) — Beneficial Effects of a Nutraceutical Combination on Lipid Profiles in Children with Moderate and Severe Hypercholesterolaemia. PMID 39766315.

10. Naiyarakseree et al. (2023) — Effect of Menaquinone-7 Supplementation on Arterial Stiffness in Chronic Hemodialysis Patients: A Multicenter Randomized Controlled Trial. PMID 37299386.

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