This guide reviews ten supplements with meaningful clinical evidence behind them — covering muscle performance, brain health, heart health, skin quality, and sleep. The supplement industry is large and often under-regulated, which makes it especially important to distinguish those with strong clinical trial evidence from those based largely on marketing claims. Each section below summarises the relevant science and the dosing used in trials, so readers can make an informed decision in consultation with a healthcare professional.
The supplements are grouped roughly by their primary benefit area: muscle performance (Supplements 1–3), brain and cognitive health (Supplements 3–5, with some overlap), heart and metabolic health (Supplements 5–6), skin quality (Supplements 7–8), sleep (Supplement 9), and cellular health (Supplement 10).
Disclaimer: Always consult with a healthcare professional before adding any new supplement to your regimen. Individual health status, existing medications, and nutritional needs vary significantly.
Table of Contents
- Supplement 1: Creatine Monohydrate
- Supplement 2: Protein Powder
- Supplement 3: Trimethylglycine (TMG)
- Supplement 4: Multivitamin and Mineral
- Supplement 5: Omega-3 Fatty Acids
- Supplement 6: Psyllium Husk
- Supplement 7: Collagen Peptides
- Supplement 8: Hyaluronic Acid
- Supplement 9: Melatonin
- Supplement 10: Glutathione Support
- References
Supplement 1: Creatine Monohydrate
Creatine monohydrate is the most extensively studied sports supplement available. The evidence is strong enough that the International Society of Sports Nutrition concluded it "is the most effective nutritional supplement currently available to athletes in terms of increasing high-intensity exercise capacity and lean body mass during training" [1].
It also supports muscle recovery after exercise [2]. Initial safety concerns about this supplement have been disproven by subsequent research. Specifically, there is no link to hair loss, creatine does not increase uric acid levels, and it poses no risks to the kidneys. It is not associated with dehydration or muscle cramping, and it increases lean muscle mass — not fat mass [3][4][5][6].
The standard trialled dose is creatine monohydrate 5 grams daily. There is no meaningful benefit to loading phases for most purposes — a consistent 5 grams per day achieves full muscle creatine saturation within 3–4 weeks without the transient water retention sometimes seen with loading protocols.
While many people focus on creatine's muscle performance effects, there is more to the picture. Ninety-five percent of the body's creatine is stored in muscles, but the remaining 5% is found in the brain, kidneys, and liver. During periods of physiological stress — including sleep disruption and the ageing process itself — brain creatine levels can decrease [7].
Research shows that creatine supplementation can restore brain creatine levels [8]. A meta-analysis combining ten studies found that creatine supplementation improved memory performance compared to placebo, with the effect being particularly strong in older adults [9]. This cognitive benefit adds a second rationale for supplementing with creatine monohydrate at 5 grams per day.
Supplement 2: Protein Powder
Protein powder is the second of three supplements in this guide recommended for muscle performance.
There is a striking correlation between decreased muscle strength and increased mortality rates, even after adjusting for other factors [10]. Maximising muscle strength in youth, maintaining it through middle age, and minimising decline in older age are therefore important health goals.
Multiple lines of evidence confirm that higher protein intake improves the muscle-building response to exercise — which is why clinical guidelines recommend increasing protein intake for those engaged in resistance training [11].
A 2018 analysis combining 49 studies found that a protein intake of 1.6 grams per kilogram of body weight per day maximised the muscle-building response from resistance exercise [12]. For an 80 kg (176 pound) person, that works out to just under 130 grams per day (128 grams) — a high target that is often difficult to reach through whole food alone.
As a point of reference, beef is roughly 25% protein by weight, meaning an 80 kg person would need to eat just over half a kilogram of beef daily to hit this target. Protein powders are a practical option to bridge the gap: the protein is highly bioavailable and can be mixed into smoothies or shakes. When selecting a powder, it is worth checking that it does not contain added sugar or salt.
An important factor when choosing protein sources is leucine content. Leucine is an essential amino acid that plays a pivotal role in initiating muscle protein synthesis. Whey protein is typically rich in leucine.
For those following a plant-based diet, achieving an equivalent leucine stimulus requires a higher overall protein intake. Pea protein is a well-studied option — rich in essential amino acids and easily digestible. Soy protein is another good choice. Despite claims circulating on social media, there is solid evidence that soy proteins do not affect testosterone or oestrogen levels in men [13].
Supplement 3: Trimethylglycine (TMG)
The third supplement for muscle performance is Trimethylglycine (TMG).
TMG works by accelerating the recycling of ATP — the cell's primary energy currency — and it supports muscle protein synthesis.
There is some controversy with this supplement. A 2017 analysis found that of the seven studies published at the time, only two reported improvements in muscle strength or power [14]. The crucial finding is that the benefits appear when TMG is combined with exercise; without exercise, no effect is observed.
The trialled dose for muscle performance is TMG 500 mg daily, taken alongside a structured exercise programme.
Beyond muscle, TMG has another intriguing potential benefit — it may support brain performance and reduce the risk of dementia. A 2020 large review of Alzheimer's disease risk factors found that high levels of homocysteine (an amino acid) were strongly linked to Alzheimer's disease, and that homocysteine-lowering treatment appears to be the most promising pharmacological intervention for Alzheimer's prevention [17].
TMG is a well-established homocysteine-lowering agent [18]. In other words, TMG may reduce a modifiable risk factor for Alzheimer's disease by lowering homocysteine levels. This is a promising area of research, though it should not be interpreted as a guaranteed prevention strategy.
Supplement 4: Multivitamin and Mineral
On the subject of brain health, the fourth supplement for cognitive performance and memory is a multivitamin and mineral supplement.
A landmark 2022 study called the COSMOS-Mind trial involved over 2,000 participants followed for three years. The group that took a multivitamin and mineral supplement showed a statistically significant improvement in global cognition compared to placebo [19]. This was a well-powered, randomised, placebo-controlled trial — the strongest form of clinical evidence.
The COSMOS-Mind evidence supports a core principle behind the MicroVitamin formulation: that reaching recommended daily intakes of key micronutrients — including B-vitamins, Vitamin D3, K2, zinc, and magnesium — is worthwhile, particularly when dietary gaps exist. A good multivitamin and mineral supplement should avoid megadosing individual nutrients, include Vitamin K2 (often omitted from mainstream products), and use well-absorbed forms for each ingredient.
There is also a tantalising prospect that combining TMG with a multivitamin and mineral supplement, together with the fifth supplement on this list, may work synergistically to support brain performance and reduce dementia risk. Let me explain.
Supplement 5: Omega-3 Fatty Acids
The fifth supplement is Omega-3 fatty acids. Research has shown that people with low homocysteine levels who supplemented with Omega-3 experienced a 7.1% improvement in brain performance and a 22.3% reduction in dementia symptoms [20].
However, for people with high homocysteine levels, Omega-3 supplementation provided no detectable benefit. This suggests that homocysteine plays a critical mediating role in the brain-health response to Omega-3 — and that achieving low homocysteine levels may be a prerequisite for Omega-3 to have a positive impact on cognitive function.
TMG and B-vitamins (found in a comprehensive multivitamin and mineral) lower homocysteine levels. More research is needed before definitive conclusions can be drawn about this three-supplement combination for brain performance, but it is a scientifically plausible and encouraging direction.
There is also a second, independent reason to supplement with Omega-3. The VITAL trial — involving over 25,000 participants — found that the Omega-3 group had a 28% reduction in the risk of heart attack compared to placebo [21]. When the Mayo Clinic pooled data from multiple separate trials, they concluded that Omega-3 supplementation is associated with a statistically significant ~13% reduction in heart attack risk, rated with high GRADE certainty [21].
As with vitamins and minerals, megadosing Omega-3 carries meaningful risks — including an increased risk of atrial fibrillation (an abnormal heart rhythm). The dose used in the trials that showed benefit without excess risk is approximately 1 gram of Omega-3 daily, as a mixture of EPA and DHA.
Supplement 6: Psyllium Husk
The sixth supplement on this list is relevant to heart health: psyllium husk. Following this, we will look at two supplements supported by evidence for reducing skin wrinkles.
Psyllium husk acts as a prebiotic fibre, feeding beneficial bacteria in the gut. Through this mechanism, research demonstrates improvements in insulin sensitivity, blood sugar levels, blood pressure, and cholesterol [22][23].
The trialled range is 3–5 grams of psyllium husk per day. When selecting a brand, it is worth paying attention to lead content — an analysis by ConsumerLab.com found that Organic India Psyllium Whole Husk Fiber had the lowest lead levels of the products tested.
Like protein powder, psyllium husk can be mixed into smoothies or shakes. It also increases satiety, helping to maintain feelings of fullness.
Supplement 7: Collagen Peptides
The seventh supplement is collagen peptides, also known as hydrolysed collagen.
Multiple clinical trials support the finding that collagen peptides reduce skin wrinkles by approximately 8% [24].
The trialled dose is 10–15 grams of collagen peptides daily.
There is a legitimate scientific question here: collagen peptides are short-chain amino acids, and amino acids are the building blocks of protein. Could simply supplementing with standard protein achieve the same skin benefits? The answer appears to be no. The body absorbs these short amino acid chains intact, and they are transported directly to the skin — a different route from larger protein molecules.
A 2020 randomised controlled trial in burn patients compared equal amounts of standard protein versus collagen peptides. The collagen peptide group experienced a significantly higher wound-healing rate, suggesting that collagen peptides offer benefits beyond those of regular protein intake [25][26].
These findings were further supported by a meta-analysis combining 23 separate randomised controlled trials, where collagen peptides were shown to improve both skin hydration and skin elasticity [27].
Supplement 8: Hyaluronic Acid
Continuing the skin health theme, the eighth supplement is hyaluronic acid.
Hyaluronic acid is a glycosaminoglycan that naturally occurs in the skin, joints, and connective tissue, where it plays a central role in maintaining moisture. Topical hyaluronic acid is widely used in skincare, but the evidence now extends to oral supplementation as well. Just like collagen peptides, there are multiple randomised clinical trials showing that oral hyaluronic acid supplementation improves skin wrinkles. A 2021 study demonstrated an 18.8% improvement in wrinkle appearance [28].
The trialled dose is 200 mg of oral hyaluronic acid daily. MicroVitamin includes hyaluronic acid at this evidence-based dose as one of its 25 ingredients, alongside the B-vitamins, minerals, and other micronutrients discussed in Supplement 4.
Supplement 9: Melatonin
The ninth supplement on the list is melatonin — for sleep quality.
Low-dose melatonin supplementation has strong evidence from human studies showing improvements in the time it takes to fall asleep and in overall sleep quality [29][30].
Timing and dose are the two critical variables. Melatonin helps regulate the sleep-wake cycle, and a low-dose supplement only produces the desired phase-shifting effect when taken approximately 2 hours before the intended bedtime [29].
Dose matters considerably. The body produces up to 80 micrograms of melatonin per hour during sleep — approximately 640 mcg across an 8-hour night. Yet many commercial melatonin supplements contain doses far in excess of this physiological level. Long-term safety data for high-dose melatonin supplementation is lacking, which is why the evidence-supported dose of 300 mcg — taken around 2 hours before sleep — is recommended in clinical literature [29].
Beyond its sleep effects, melatonin also has antioxidant and anti-inflammatory properties. These properties are particularly relevant in the context of the ageing process [31].
From the MicroVitamin range
The Sleep supplement combines melatonin at the evidence-supported 300 mcg dose with magnesium bisglycinate and glycine — two ingredients with independent evidence for supporting sleep quality and duration. Learn more about Sleep by Dr Brad.
Supplement 10: Glutathione Support
From around the age of 45, levels of glutathione — one of the body's most powerful endogenous antioxidants — begin to decline significantly [32]. Supplementing with the biochemical building blocks of glutathione (rather than glutathione itself, which has poor oral bioavailability) allows the body to regulate its own glutathione production.
A 2022 study examined this approach in older adults, providing a combination of glycine and N-acetylcysteine (NAC) supplements versus placebo. The glycine and NAC group showed significant improvements in mitochondrial health markers [33].
Of all ten supplements discussed in this guide, glutathione support has the least accumulated evidence. The research is early-stage, and more replication is needed before strong clinical recommendations can be made. That said, for adults over 45, a glycine and NAC supplement at around 1 gram of each daily is a reasonable area to investigate in consultation with a healthcare professional — particularly given that glutathione precursor supplementation has a relatively low risk profile at these doses.
Summary: The Evidence Hierarchy Across These 10 Supplements
Not all supplements on this list carry equal evidence. A useful way to approach the list is by evidence tier:
- Strongest evidence (multiple large RCTs or meta-analyses): Creatine monohydrate, protein powder, Omega-3 fatty acids, psyllium husk, collagen peptides.
- Good evidence (at least one large well-powered RCT): Multivitamin and mineral (COSMOS-Mind, n=2,100+), hyaluronic acid, melatonin at low dose.
- Promising but early (small trials, mechanistic plausibility): TMG for muscle and homocysteine, glycine + NAC for glutathione support.
The goal of evidence-based supplementation is not to take everything that has any positive study — it is to identify the small subset of supplements where the evidence is genuinely compelling and the risk is low. The ten listed here represent that subset as of 2025.
Always consult with a healthcare professional before adding any new supplement to your routine. Individual health status, medications, and needs vary significantly.
References
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- https://jissn.biomedcentral.com/articles/10.1186/s12970-017-0173-z
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- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8912287/
- https://academic.oup.com/nutritionreviews/advance-article/doi/10.1093/nutrit/nuac064/6671817
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- https://www.uptodate.com/contents/practical-guidelines-for-implementing-a-strength-training-program-for-adults
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867436/
- https://pubmed.ncbi.nlm.nih.gov/33383165/
- https://pubmed.ncbi.nlm.nih.gov/28426517/
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- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569385/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3610948/
- https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.12767
- https://pubmed.ncbi.nlm.nih.gov/30958356/
- https://www.mayoclinicproceedings.org/article/S0025-6196(20)30985-X/fulltext
- https://www.sciencedirect.com/science/article/pii/S1756464623004784
- https://www.cochrane.org/CD011472/VASC_dietary-fibre-prevent-cardiovascular-disease
- https://pubmed.ncbi.nlm.nih.gov/36516059/
- https://pubmed.ncbi.nlm.nih.gov/31859087/
- https://eprints.iums.ac.ir/24135/1/The-effect-of-a-hydrolyzed-collagenbased-supplement-on-wound-healing-in-patients-with-burn-A-randomized-doubleblind-pilot-clinical-trial2020Burns.pdf
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10180699/
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- https://academic.oup.com/biomedgerontology/advance-article/doi/10.1093/gerona/glac135/6668639
