Supplement Guide | Biomarkers 02 | 7 Biomarkers Supplements Can Actually Move (Plus a bonus)

This is Part 2 of SuppCo's four-part series on biomarkers and supplements. The series covers everything from how to interpret your results to the specific markers most relevant to supplement users… and what the evidence actually says about moving them.

To read part 1 in the series, click here.

Blood work tells a story. The question is whether anyone helps you read it.

After years studying how nutrients interact with human physiology, the biomarkers that genuinely respond to supplementation, and the ones that don't, have become pretty clear to me. Today I'm sharing seven of them, paired with the nutrients that have real clinical data behind them.

This isn't exhaustive. It's curated. A mix of the familiar and the underappreciated, with honest context about where the evidence is stronger and where it's still developing.

Your lab results are only useful if they change how you act. Here's where supplements may help  move the needle.

1. Low Vitamin D → Vitamin D3 + K2

The marker: 25-hydroxy Vitamin D, or 25(OH)D, the standard measure of vitamin D status. The typical reference range is 30-100 ng/mL, while the optimal range sits at 45-100 ng/mL.  An estimated 41% of Americans are low in vitamin D.

The supplement: Vitamin D3 (cholecalciferol) is the form your skin makes when exposed to sunlight. It has been shown to raise 25(OH)D more effectively than D2, the plant-derived form found in other supplements. D3 can also be paired with vitamin K2. K2 may help direct calcium to bones rather than soft tissue, which matters when you're supplementing D3 at meaningful doses.

The evidence: A 2023 systematic review and meta-analysis in Advances in Nutrition covering 20 comparative studies found D3 to be superior to D2 in raising total 25(OH)D concentrations, with D3 raising levels roughly 40% more than D2 in daily dosing trials.

The caveat: Raising vitamin D is straightforward. Translating various levels to different outcomes is a more nuanced conversation. The marker is movable. The downstream health benefits may depend on your baseline and your biology.

2. Low Ferritin → Iron Bisglycinate

The marker: Ferritin reflects the body’s stored iron levels and appears to be a more sensitive early indicator of iron depletion than hemoglobin. It is possible to have low ferritin while your hemoglobin still looks fine. Many people may walk around with iron deficiency for years before a doctor flags it.

The supplement: Iron bisglycinate, also called ferrous bisglycinate. Iron chelated to the amino acid glycine is thought to be more bioavailable than conventional iron salts. In many people, it’s associated with  fewer gastrointestinal side effects… which is one reason people abandon iron supplementation.

The evidence: A 2023 systematic review and meta-analysis in Nutrition Reviews covering 17 RCTs found ferrous bisglycinate produced greater improvements in hemoglobin concentrations in pregnant women compared to other iron supplements, with a 64% lower rate of gastrointestinal adverse events versus conventional iron salts. In addition, this pilot study showed a significant improvement in ferritin with iron bisglycinate supplementation

The caveat: Before supplementing, it helps to know the levels of your iron-related markers.  Excess iron supplementation is problematic. Testing can give you more information about where you stand.

3. High Fasting Glucose → Berberine

The marker: Fasting plasma glucose can be a signal of metabolic dysfunction. Even mildly elevated fasting glucose, in the 100 to 125 mg/dL range that defines prediabetes, significantly raises long-term cardiometabolic risk. Most people in that range don't know they're there.

The supplement: Berberine, a plant-derived alkaloid found in several botanical species. It activates an enzyme called AMPK, the same energy-sensing pathway targeted by metformin, the most commonly prescribed diabetes medication in the world. That mechanism is why berberine gets compared to metformin as often as it does.

The evidence: A 2023 meta-analysis in the Journal of Nutrition covering 20 RCTs and 1,761 participants found berberine meaningfully reduced both fasting blood sugar and HbA1c, the two-to-three month blood sugar average your doctor uses to screen for prediabetes and diabetes, versus placebo. The fasting glucose reduction translates to roughly 9 mg/dL. To put that in context: the typical reference range is 65-99 mg/dL. The prediabetes threshold begins at 100 mg/dL, just one point above the top of the range. A 9-point move is meaningful.

The caveat: When discussing glucose, diet and lifestyle are key considerations. Berberine interacts with several medications, including blood thinners and some antibiotics. It should also be avoided by those who are pregnant or breastfeeding. If you're taking prescription medications for glucose or lipid management, talk to your doctor before adding it.

4. Low RBC Magnesium → Magnesium Glycinate

The marker: Red blood cell magnesium, not serum magnesium. This distinction matters. Serum magnesium is tightly regulated and can stay in a normal range even when overall stores are low. RBC magnesium reflects actual cellular stores. You can have a normal serum reading and still be functionally deficient. Function provides access to RBC magnesium. Many standard panels do not.

The supplement: Magnesium glycinate, magnesium bound to the amino acid glycine. Of all the magnesium forms available, organic chelates like glycinate are more bioavailable than inorganic forms like oxide or sulfate, and far less likely to cause the laxative effect that makes people abandon magnesium supplementation.

The evidence: A 2025 systematic review and meta-analysis in Antioxidants covering 28 studies confirmed that organic magnesium formulations including glycinate are more bioavailable than inorganic forms, and that magnesium supplementation produced a statistically significant reduction in CRP levels across the included trials.

The caveat: Magnesium does a lot of things, which makes it one of the more credibly useful supplements on this list. The problem is that marketing has overclaimed it. Focus on the basics: sleep quality, muscle function, and metabolic health are where the evidence is strongest.

5. High Triglycerides → Omega-3 (EPA/DHA)

The marker: Fasting triglycerides. Elevated triglycerides, typically at or above 150 mg/dL, are a risk factor for cardiovascular disease and a common signal of broader metabolic dysfunction. They're also one of the most reliably supplement-responsive markers on this list.

The supplement: Omega-3 fatty acids, specifically EPA and DHA from fish oil. Dose matters here. The effect on triglycerides at a standard 1g/day dose is modest. At 3 to 4g/day, it becomes meaningful.

The evidence: A 2025 dose-response meta-analysis in Food Science & Nutrition covering 20 reports and 1,685 participants confirmed a statistically significant, dose-dependent reduction in triglycerides with omega-3 supplementation, with some studies showing that daily intake of 3 to 4g EPA and DHA reduced triglyceride levels by 20 to 50% in individuals with elevated baseline levels.

The caveat: Many fish oil supplements sold at retail are dosed nowhere near the amounts needed to move triglycerides meaningfully. Check the EPA and DHA content on the label, not the total fish oil weight. Those are not the same number. Caution is recommended for those taking certain medications, including blood thinners. 

6. Elevated Cortisol → Ashwagandha (KSM-66)

The marker: Serum cortisol, measured in the morning when levels peak. Chronically elevated cortisol is associated with disrupted sleep, impaired glucose regulation, immune suppression, and accelerated aging at the cellular level. It's a common finding in people who are overscheduled, under-recovered, and running on caffeine. I'm not naming any names.

The supplement: Ashwagandha, specifically the KSM-66 extract, a standardized full-spectrum root extract that has been studied more rigorously than most other ashwagandha preparations. It's classified as an adaptogen, meaning it helps modulate the stress response rather than simply blunting it.

The evidence: A double-blind placebo-controlled RCT published in the Indian Journal of Psychological Medicine found that subjects taking high-concentration full-spectrum ashwagandha root extract showed significant reductions across all stress-assessment scales by day 60, with serum cortisol levels substantially reduced versus placebo. Another meta-analysis of 22 RCTs (n=1391) further supported that ashwagandha root helped support mood and stress resilience in this population.

The caveat: Ashwagandha may be particularly helpful in those whose systems are genuinely stressed with elevated cortisol. Test first, then decide.

7. Elevated hs-CRP → Urolithin A

The marker: High-sensitivity C-reactive protein (hs-CRP), one of the most commonly tested inflammation markers. Chronically elevated hs-CRP is associated with cardiovascular disease, metabolic dysfunction, and accelerated biological aging. It's also a marker that many people have elevated, without knowing exactly why.

The supplement: Urolithin A, a compound produced when gut bacteria metabolize ellagitannins found in pomegranates, walnuts, and certain berries. Here's the twist: many people's gut microbiomes only produce small amounts of urolithin A from diet alone. That's why supplementing the compound directly has become a serious area of research.

One of its mechanisms is genuinely novel. Urolithin A activates mitophagy, the cellular process by which damaged mitochondria get broken down and recycled. Think of it as cellular housekeeping at the energy-production level. Better mitochondrial quality means more efficient energy output, less oxidative stress, and, as the research is starting to show, measurably lower inflammation.

The evidence: A double-blind placebo-controlled RCT published in Cell Metabolism found that urolithin A supplementation over four months helped produce approximately 12% improvements in muscle strength, clinically meaningful improvements in VO2 and physical performance, significantly lower plasma acylcarnitines indicating higher mitochondrial efficiency, and reduced CRP versus placebo.

The caveat: Urolithin A research is newer than the other entries on this list. The Cell Metabolism trial is high quality, but the field is still building its evidence base. The mitophagy mechanism is well-established in the literature. The clinical translation is compelling. This one belongs on your radar even if you're not ready to act on it yet.

Bonus: Elevated Lp(a) → Niacin

The marker: Lipoprotein(a), or Lp(a). If you've had testing done and you found an elevated Lp(a) on your results, you may have felt the same mild dread I did when I saw mine. Lp(a) is a modified form of LDL with a protein attached that makes it more likely to stick to arteries, trigger inflammation, and promote plaque buildup. It is largely genetically determined. You mostly inherited this number. That's the hard truth.

The supplement: Niacin, specifically nicotinic acid. This is, to me, the most interesting entry on this list, because the story here is still unfinished. What we know is that niacin is one of the very few non-pharmaceutical interventions with meta-analytic evidence for actually moving Lp(a). What we don't know is whether moving Lp(a) with niacin translates to reduced cardiovascular events.

The evidence: A meta-analysis published in Metabolism covering 14 randomized placebo-controlled trials and over 9,000 subjects found extended-release niacin produced a mean Lp(a) reduction of approximately 23%, consistent across both lower and higher dose ranges.

The caveat: I want to be direct here. The science on Lp(a) reduction as a cardiovascular strategy is still evolving. The AIM-HIGH trial, which looked at niacin's effect on cardiovascular outcomes, was stopped early and did not show a meaningful benefit over statin therapy alone. There are also tolerability issues with high-dose niacin, including flushing, and the extended-release form has its own considerations.

That finding is part of a larger pattern: a systematic review and meta-analysis of 13 randomized controlled trials covering over 35,000 patients found niacin did not produce significant reductions in all-cause mortality, cardiovascular mortality, heart attack, stroke, or revascularization compared to control. 

Niacin may lower Lp(a), but lowering Lp(a) with niacin has not been shown to translate into fewer cardiovascular events. There are also tolerability issues with high-dose niacin, including flushing, and the extended-release form has its own considerations. None of this means the conversation is over. 

If your Lp(a) is elevated, it's worth knowing that there is an intervention with a 23% reduction signal in a large meta-analysis. It's also worth having a conversation with your doctor about what, if anything, to do with that information. This one is genuinely complicated, and anyone who tells you otherwise is oversimplifying.

The common thread across all of these is the same: a blood test alone won’t make changes. What you do with the number is what matters. The bottleneck for many people is the distance between a lab result and a decision.

For what it's worth, much of this list lives in my own supplement cabinet. Vitamin D, fish oil, berberine, urolithin A, and ashwagandha on the harder weeks. I built my stack the same way I'm suggesting you build yours: I looked at my numbers, I read the studies, and I made decisions I could defend.

The Lp(a) one is still unresolved for me personally. I found my number, I went deep in the literature, and I landed somewhere between cautious optimism about the niacin signal and genuine humility about how much we still don't know. Lowering Lp(a) is great, but if it doesn’t result in actual reductions in cardiovascular events, is it still useful? I'm hoping that working at the intersection of Function’s testing data and SuppCo's supplement science gets us closer to a cleaner answer. For me and for a lot of other people carrying that same number quietly.

Closing that gap is the whole idea behind what SuppCo and Function are building together, and this piece is where that work starts in earnest. There's a lot more coming. This is the work I came here to do. I'm glad we're finally doing it together.