Dr. Will Cole's Supplement Protocol: The Gut-Brain Inflammation Stack, Available at X-Optimum

Editorial still life of botanical extracts and laboratory glassware for a functional medicine supplement protocol

Dr. Will Cole is a Pittsburgh-based functional medicine practitioner known for Ketotarian, The Inflammation Spectrum, Gut Feelings, and The Art of Being Well. His public writing treats the gut, brain, adrenals, and hormone axis as one circuit, not four separate wellness hobbies.

This article is an educational map of compounds Cole discusses openly on his site and in his own supplement line (probiotics, magnesium, omega-3s, curcumin, ashwagandha-class adaptogens, B vitamins, vitamin D). It is not an endorsement, not a clinic protocol, and not a claim that Cole uses X-Optimum products.

If you want the biological hardware version of that map, start with the overlaps below. Honest gaps stay honest: X-Optimum does not sell standalone fish oil, magnesium, DIM, NAC, or vitamin D.

Cole's core idea: inflammation is a spectrum, not a diagnosis

Cole's public framing is that low-grade inflammatory load, gut barrier stress, and HPA-axis overdrive show up as brain fog, sleep disruption, skin flares, and hormone noise long before anyone gets a dramatic lab flag. The job of a stack, in that model, is to lower the load and restore inputs: microbiome signaling, cortisol buffering, micronutrient cofactors, and sleep architecture.

That is a systems problem. Stimulant energy drinks do not solve it.

1. Probiotics and the gut-brain circuit

Cole sells The Probiotic and writes that microbiome balance influences estrogen metabolism, immune tone, calcium absorption, and mental health. In menopause writing he lists probiotics among his top sixteen recommendations because the gut is part of the estrogen-clearance and immune hardware, not a side note.

Mechanistically, selected strains can shift short-chain fatty acid production, tighten epithelial signaling, and communicate with the vagus-brain axis. That is why "gut first" shows up in his books even when the presenting complaint is mood or skin.

X-Optimum overlap: Optimized Super Probiotic ($17.99). Use this as the microbiome tool. It is not Cole's formula and is not a 1:1 strain match.

Support layer if you want plant polyphenols around the same meal: Superfood Greens Formula ($19.99) and Superfood Reds Formula ($19.99).

2. Adaptogens: ashwagandha, ginseng, maca, HPA buffering

On menopause and stress pages, Cole highlights ashwagandha for resilience and sleep continuity, Korean ginseng for stress-linked hot flashes and mood swings, and maca as a traditional adaptogen for energy and libido under load. He also sells The Brain-Adrenal Balancer and a calming mix (Chill) with magnesium, taurine, and L-theanine.

Ashwagandha (Withania somnifera) is studied for cortisol buffering and sleep efficiency. Ginseng and maca are weaker, more mixed evidence, but they sit in the same "stress hardware" bucket he uses publicly.

X-Optimum overlap:

Gap: no standalone maca, ginseng, L-theanine, or taurine SKU.

3. Sleep architecture (magnesium, theanine, ashwagandha)

Cole repeatedly treats sleep as repair time, not a luxury. He lists magnesium for anxiety, tension, and calcium absorption; L-theanine for GABA/serotonin/dopamine tone; and ashwagandha for sleep efficiency. His travel writing starts with magnesium.

X-Optimum does not sell elemental magnesium. Adjacent tools:

Do not pretend these replace a measured magnesium glycinate protocol. They are sleep-support formulas in the same biological neighborhood.

4. B vitamins, methylation, and cognitive cofactors

Cole's menopause list includes B vitamins for nervous-system and cardiovascular risk, B6/B12 for cognitive aging, and folate for mood. His shop includes The Methylator (methylation support) and CoQ10.

This is cofactor logic: one-carbon metabolism, neurotransmitter synthesis, and mitochondrial electron transport. It is not a "energy gummy" story.

X-Optimum overlap:

Gap: no dedicated methylated B-complex or CoQ10 product.

5. Hormone-adjacent botanicals (DIM, isoflavones, milk thistle)

Cole discusses DIM (cruciferous estrogen metabolism), isoflavones as phytoestrogens for hot flashes, and milk thistle (silymarin) for liver estrogen clearance. He is explicit that some botanicals mimic estrogen and that people on hormone therapy or with estrogen-sensitive conditions need a clinician.

X-Optimum does not sell DIM, soy isoflavones, or milk thistle isolates. Closest catalog tools for women who want a broader hormone-support multi, not a DIM clone:

That is a genuine overlap on "women's micronutrient + botanical support," not a chemical match to DIM.

6. Curcumin, glutathione, and oxidative load

Cole's shop includes The Curcumin, Liposomal Glutathione, and NAC in educational menopause writing as a glutathione precursor. Curcumin is a well-studied NF-kB-adjacent anti-inflammatory; glutathione is the cell's primary thiol antioxidant.

X-Optimum overlap on polyphenol/antioxidant tone, not on NAC or glutathione:

Gap: no curcumin isolate, NAC, or glutathione.

7. Structural protein: collagen as connective-tissue input

Cole's public menopause article does not center collagen the way his gut/skin writing centers barrier health, but connective tissue, skin, and joint load sit inside the same inflammation-spectrum story. Hydrolyzed collagen peptides supply glycine, proline, and hydroxyproline used in extracellular matrix.

X-Optimum overlap: Grass-Fed Bovine Collagen Peptides Powder (Chocolate) ($24.99).

8. What Cole emphasizes that X-Optimum does not sell

Keep this list visible so the article stays honest:

  • Magnesium (his shop SKU and travel staple)
  • Omega-3 / The Omega+
  • Vitamin D3-K2
  • DIM, isoflavones, black cohosh, inositol, taurine, L-theanine as singles
  • NAC, liposomal glutathione, CoQ10, berberine

If those are non-negotiable in a Cole-style protocol, buy them from a clinician-grade source. Do not stretch X-Optimum SKUs to cover them.

Build Your Gut-Brain Inflammation Stack at X-Optimum

Cole's public message is unglamorous: fix the gut, buffer the stress axis, fill micronutrient gaps, protect sleep, then argue about exotic compounds. X-Optimum can cover the probiotic, adaptogen, sleep-formula, multi, polyphenol, mushroom, and collagen layers of that map.

Start here: browse the full catalog.

Work with a qualified clinician before stacking botanicals that touch estrogen, methylation, or liver enzymes, especially if you are on HRT, thyroid medication, or anticoagulants.

Disclaimer: X-Optimum Wellness has no affiliation with Dr. Will Cole, The Art of Being Well, Ketotarian, or his clinical practice. This article references publicly available information from Dr. Will Cole's interviews, podcast, blog, shop, and published works for educational purposes. Always consult a qualified healthcare provider before beginning any new supplement protocol.