David Sinclair's Blood Test Protocol: The Markers He Tracks and Why

David Sinclair, a genetics professor at Harvard Medical School and author of Lifespan, runs a narrower blood protocol than most longevity physicians, focused on two markers directly tied to his NMN, resveratrol, and off-label metformin stack. Below are the markers he tracks, his stated targets, and the scientific pushback his central mechanism has received.

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Compiled by AI from the named experts’ own public statements, with every figure attributed to its source. These are individual expert protocols, not clinical guidelines or FixFirst medical advice. Evidence & methodology

Targets attributed to Sinclair, sourced Scientific controversy documented Free 45-second analysis of your own results

Why Sinclair's protocol is narrower than Attia's

Sinclair's blood monitoring is built around his supplement and drug stack, not a broad lifespan biomarker panel. The two markers he reports tracking are both directly implicated by what he takes.

This page is part of FixFirst's Longevity blood markers series, which attributes every target to the person who cited it rather than presenting it as clinical guidance. Unlike Peter Attia's 16-marker panel, Sinclair's published protocol is specific to his own stack. The targets below trace to his 2019 book Lifespan and subsequent interviews.

Homocysteine and B12 are markers FixFirst checks automatically if they appear on your report — against standard clinical ranges, not Sinclair's stack-specific targets. If you are taking metformin for any reason, B12 monitoring is standard medical practice regardless of what else you supplement. For the full narrative context — the sirtuin controversy, the resveratrol critique, and how the numbers compare — see the commentary post on his protocol.

The markers Sinclair reports tracking

Two blood markers, both tied to specific pathways in his protocol — one for methylation, one as a metformin side-effect check.

Cluster 1 of 2

Methylation and NAD+ pathway

Sinclair's research focuses on NAD+ pathways and sirtuins. Homocysteine sits at the intersection of methylation and the B-vitamin cycle, and high homocysteine is associated with impaired methyl-group availability, which is why he monitors it alongside his NMN supplementation. His target is stricter than the standard clinical cut-off of 15 µmol/L.

Core Usually in a standard panel Ask Request specifically

Core

Homocysteine

Sinclair targets homocysteine under 8 µmol/L, versus the standard clinical high-risk threshold of 15 µmol/L. He reports this in the context of his NMN and folate supplementation stack. It is his own stated personal target, not a guideline number — the standard clinical reference range is wider.

Cluster 2 of 2

Drug side-effect monitoring

Sinclair takes 800 mg/day of metformin off-label for its reported effects on longevity-linked pathways. Metformin is a documented B12 depleter via the ileal transporter mechanism, which is the specific reason B12 needs monitoring on this protocol. This is not a general wellness check.

Core Usually in a standard panel Ask Request specifically

Ask

Vitamin B12

B12 monitoring is on Sinclair's list because metformin depletes it — not as a general nutritional marker. He has reported his own B12 running to roughly double the recommended maximum after supplementing to counter the depletion, an example of the correction overshooting. Standard clinical guidance recommends B12 monitoring for anyone on long-term metformin.

Frequently asked questions

What blood markers does David Sinclair track?

Sinclair reports tracking homocysteine (target under 8 µmol/L) and B12 as the two blood markers most directly tied to his protocol. Homocysteine is linked to the NAD+ and methylation pathways his research focuses on; B12 monitoring exists because metformin, which he takes off-label, is a known B12 depleter.

Why does David Sinclair monitor B12?

Sinclair monitors B12 specifically because he takes metformin off-label at 800 mg/day. Metformin depletes B12 via the ileal transporter mechanism in the gut. It is not a general wellness check — the monitoring is a direct counter to a documented side effect of the drug.

Is Sinclair's homocysteine target based on clinical guidelines?

No. Sinclair's stated target of under 8 µmol/L is stricter than the standard clinical high-risk cut-off of 15 µmol/L. It is his own personal protocol number, tied to his NMN and methylation-pathway supplementation, not a threshold any clinical guideline publishes for the general population.

What is the scientific criticism of Sinclair's sirtuin research?

In January 2023, NAD+ researcher Charles Brenner published a peer-reviewed letter in Archives of Gerontology and Geriatrics arguing that sirtuins do not extend lifespan in yeast or flies, and that the assay used to show resveratrol activating sirtuins produces a false positive. Brenner also notes that the original resveratrol lifespan effect was observed only in mice fed a calorie-dense diet, not in mice on a normal one.

Does Sinclair's protocol compare to Peter Attia's blood work?

Attia's panel covers 16 markers across metabolic health, lipids, inflammation, liver, kidney, and hormones — a broad lifespan monitoring approach. Sinclair's published protocol is narrower: two markers (homocysteine and B12) that are specifically relevant to his supplement and drug stack. Both are expert protocols, not clinical guidelines.

Keep reading: Peter Attia's Blood Test Panel · Casey Means's Blood Test Panel · Longevity blood markers hub

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