Video Interview - Nitric Oxide and Functional Health - with Dr. Nathan Bryan

#81

My prompt to CGPT5:

Please summarize and critique the scientific and clinical evidence that fluoride from toothpaste impacts nitric oxide levels in the human body

GPT5 Response:

Here’s a concise, evidence-based read on whether fluoride from toothpaste affects nitric oxide (NO) in humans.

What we actually know

  1. Direct human evidence from toothpaste exposure is basically absent. I couldn’t find randomized trials or well-controlled human studies that tested fluoridated toothpaste (vs. non-fluoridated) and then measured systemic or salivary NO (or nitrite/nitrate) as outcomes. Most human NO work in oral care focuses on antiseptic mouthwashes—which can blunt the oral nitrate→nitrite→NO pathway—rather than on fluoride dentifrices.
  2. There is human evidence from high-fluoride environmental exposure, but it doesn’t map neatly to toothpaste. A case-control study in endemic fluorosis reported elevated serum NO with chronic fluoride exposure; that is the opposite direction of the common claim that fluoride suppresses NO. Exposure levels were from water, not brief toothpaste contact, and many confounders exist. Treat this as not generalizable to toothpaste.
  3. Cell and animal data suggest fluoride can perturb endothelial NO signaling—at sufficiently high or prolonged exposure. In endothelial cell models, sodium fluoride suppressed NO synthesis by interfering with PI3K/Akt-eNOS signaling and increasing oxidative stress; broader toxicology reviews likewise note enzyme inhibition and redox stress with fluoride. These are mechanistic signals, not proof that tooth-brushing doses matter systemically.
  4. Oral-microbiome angle: mixed and indirect for fluoride. Well-documented: antiseptic mouthwashes reduce nitrate-reducing bacteria and lower NO bioavailability/blood nitrite in humans. For fluoride dentifrices, a 2022 longitudinal microbiome study found community shifts (including periopathogen changes) after brushing with fluoride or fluoride+arginine, but it did not measure nitrate-reducing capacity or NO biomarkers. So we don’t have a clean line from “fluoride toothpaste → fewer nitrate reducers → lower NO.”

Bottom line (strength of evidence)

  • Claim: “Fluoride toothpaste lowers human NO.” Not proven. No trials show this; mechanistic data are suggestive only at higher/longer exposures than tooth-brushing. Human data from high-fluoride water even report higher serum NO (likely a stress response) and aren’t applicable to toothpaste.
  • Claim: “Fluoride toothpaste kills nitrate-reducing bacteria and blunts the oral NO pathway.” Uncertain. Mouthwash evidence is strong; fluoride-dentifrice evidence is insufficient. One study shows microbiome shifts with fluoride/fluoride+arginine but no NO outcomes.

How I’d interpret this (critique)

  • External validity problem: Endothelial cell and animal findings use continuous exposure and concentrations that don’t mirror the short contact/expectoration of brushing. Extrapolating those effects to real-world toothpaste use risks dose-, route-, and time-mismatch errors.
  • Confounding in human environmental studies: Regions with endemic fluorosis differ in diet, water chemistry, and co-exposures; elevated serum NO could reflect oxidative/inflammatory stress, not healthy NO bioavailability.
  • Missing outcomes: For the oral-microbiome pathway, the outcomes that matter are salivary nitrate→nitrite conversion, plasma nitrite, and BP/vascular responses. Those have been measured for antiseptic mouthwash(showing harm to the pathway) but not for fluoride toothpastes.

Practical takeaways (given current data)

  • If your goal is to maximize NO via the oral pathway, the best-supported step is to avoid antiseptic mouthwashesthat indiscriminately suppress nitrate-reducing bacteria. Fluoride toothpaste has no clear evidence of the same effect.
  • For cautious users, microbiome-friendly practices (dietary nitrate from beets/leafy greens; avoiding broad-spectrum antiseptics unless medically indicated) have human evidence for supporting the pathway; fluoride toothpaste remains neutral/unknown for NO.

What would settle this

  • A crossover RCT comparing fluoride vs. non-fluoride toothpaste, controlling for diet and mouthwash, with salivary nitrate→nitrite, plasma nitrite, and BP as outcomes over several weeks.
  • Parallel 16S/metagenomic profiling focused on nitrate-reducing taxa (e.g., Neisseria, Rothia, Veillonella) and functional assays of nitrate-reduction capacity.

Key sources

  • Antiseptic mouthwash blunts oral NO pathway in humans: reviews and clinical data.
  • Fluoride and endothelial NO (mechanistic): HUVEC study; toxicology review.
  • Human high-fluoride exposure & serum NO (not toothpaste): endemic fluorosis study.
  • Fluoride dentifrice alters oral microbiome (no NO outcomes): longitudinal study.
  • Nitrate-NO oral pathway background & microbiome evidence: recent reviews.

Verdict: As of now, there’s no convincing human clinical evidence that ordinary use of fluoride toothpaste suppresses nitric-oxide bioavailability. The concern is biologically plausible at high/continuous exposures, but unproven for real-world brushing.

#82

Related:

Prompt:

Can you list all the beet root powder products that provide good nitric oxide benefits to humans, have know amounts of nitrites

Response

Short answer: only two beetroot powder products have published, batch-tested nitrite (NO₂⁻) amounts I can point to:

Product (form) Measured nitrate per serving (mmol) Measured nitrite per serving (mmol) Notes
HumanN SuperBeets (powder) 1.03 0.14 Independent lab testing of retail lots; relatively low nitrate vs. shots/juices.
HumanN BeetElite (powder) 2.16 ± 0.28 0.22 ± 0.01 Highest nitrite among powders tested; still below the common ≥5 mmol nitrate “performance/BP” threshold per reviews.

Why just these two?

An independent analysis of 24 commercial beet products (powders, mixed drinks, concentrates, bulk juices) quantified both nitrate and nitrite per serving. Almost all products had very little nitrite, except the two powders above (SuperBeets, BeetElite). The same paper lists per-serving nitrate for each product.

Will they deliver “good nitric-oxide benefits”?

  • Most human BP/exercise benefits in the literature show up around ~5 mmol nitrate per dose (sometimes more), which many beet shots/juices reach—but most powders (including SuperBeets and BeetElite) do not at the label serving. (BeetElite is closer; some users double-dose.)
  • The same study notes SuperBeets raises plasma nitrite faster (likely due to its nitrite content) but did not lower BPwithout enough accompanying nitrate.

“Harmful potential other compounds”?

  • The referenced lab survey specifically chose products without added vasoactive agents (e.g., L-arginine) to isolate beet effects. Both entries above fit that criterion in the tested configurations. (Always re-check current labels for sweeteners/flavors and avoid blends with stimulants.)
  • Oxalates are inherent to beets (not an “add-in”); if kidney-stone risk is a concern, moderate total intake or favor lower-volume concentrates/shots that achieve the target nitrate with less powder by weight. (General background from reviews of beetroot nitrate in humans.)

If you’re optimizing for effect size (not just nitrite labeling)

  • Consider beetroot shots/juices with ≥5 mmol nitrate/serving (e.g., Beet It Sport shots), which had ~0 nitrite in testing but consistently hit the nitrate dose linked to BP/exercise benefits in trials. These are not powders, so they fall outside your strict ask—but they’re the format most often used in positive RCTs.

Practical picks (based on your criteria)

  • Beetroot powders with known nitrite:
    1. HumanN BeetElite — best match (highest measured nitrite among powders; moderate nitrate).
    2. HumanN SuperBeets — measurable nitrite but low nitrate per serving; benefits may require higher intake or pairing with nitrate-rich diet.

Here are several commercial beetroot shots/juices with known (or clearly stated) nitrate contents, plus current list-price information where available. Note: Prices may vary by region, promotions, shipping, etc.

Product Serving size Nitrate content Price (USD approx) Notes
BEET IT Sport Nitrate 400 Shot 70 mL 400 mg (~6.45 mmol) as stated by manufacturer. ~$49.99 for pack of 15 (i.e., ~$3.33 per shot). Concentrated beetroot juice; popular in athlete studies.
UMARA U Nitrate Shot 60 mL 500 mg (~8 mmol) as stated. ~€24.50 (~US$26-30) for the single (or packs) depending on region. Higher nitrate dose; marketed for performance.
6d Sports Nutrition Nitrate Shot (Fruit Punch) unspecified (shot format) 500 mg nitrate per serving. €23.50 (~US$25-30) for one; pricing region-dependent. Contains beetroot + Amaranthus leaf extract; sports-focused.
BEET IT “Organic Beet Juice Shot” (pack of 12) unspecified size (shot) 400 mg nitrate per shot (same brand as above) ~$49.99 for pack of 12 (US) Similar brand, slightly different format.

Additional notes & caveats:

  • The literature review shows that commercial beetroot juices not those standardized shots can vary widely in nitrate content (some as low as ~0.8 mg/mL, others much higher) depending on batch, storage, season.
  • The “optimal” nitrate dose for physiological/vascular or exercise benefit is often cited around ~5 mmol (~310 mg nitrate) or higher.
  • A product may state a nitrate number, but actual measured nitrite or bio-conversion to nitric oxide (NO) may differ.
  • Price per serving needs to be calculated if pack size and share vary.
  • Always check for additions (sugar, additives) and certifications if you’re using for performance or clinical/health purposes.

Here’s a concise, evidence-based snapshot of beetroot shots/juices with known nitrate doses and current list/retail prices I could verify. I’ve shown nitrate both as mmol (from the independent lab paper) and mg (1 mmol ≈ 62.0 mg), plus a quick “cost per 100 mg nitrate” to make comparisons easy.

Note: When a product’s nitrate comes from the 2019 Int J Sport Nutr Exerc Metab lab analysis, I cite that paper; when it comes from the brand label, I cite the brand page. Prices are current examples from official shops or major retailers and may vary by region.

Product Serving size Nitrate per serving (mmol / mg) Dose source Price (currency) Price basis Cost / 100 mg nitrate
Beet It Sport Nitrate 400 Shot 70 mL shot 6.41 mmol / ~398 mg Independent lab paper $49.99 pack of 15 (=$3.33/shot) ~$0.84
Beet It Organic Beetroot Shot 70 mL shot 5.93 mmol / ~368 mg Independent lab paper ≈$37.42 pack of 15 on recent listing (≈$2.49/shot) ~$0.68
CherryActive BeetActive 30 mL shot 3.93 mmol / ~244 mg Independent lab paper £35.76 case 24×30 mL (≈£1.49/shot) ≈£0.61
Red Ace Organic Beet Performance Shot 60 mL (2 oz) 2.76 mmol / ~171 mg Independent lab paper $4.99 single 2 oz shot (HEB) [oai_citation:7‡H-E-B Here Everything’s Better](https://www.heb.com/product-detail/red-ace-organic-beet-performance-supplement/2059792?utm_source=chatgpt.com)
6d Sports Nutrition Nitrate Shot 100 mL shot ~8.06 mmol / ~500 mg Brand label(lists 500 mg nitrate/shot) €23.50 6×100 mL pack (≈€3.92/shot) ≈€0.78
Amacx Beet Shot 60 mL shot ~8.06 mmol / ~500 mg Brand label(500 mg/shot) €29.95 12×60 mL (≈€2.50/shot) ≈€0.50
Umara U Nitrate 60 mL shot ~8.06 mmol / ~500 mg Brand label(500 mg/shot) from ~€2.40 per 60 mL shot on Umara FI store; also regional resellers list local prices ≈€0.48
Lakewood Organic Beet Juice 500 mL* 18.77 mmol / ~1,163 mg Independent lab paper (500 mL basis) $10.19 32 oz (946 mL) bottle at Earth Fare (≈$5.39 per 500 mL) ≈$0.46 (per 500 mL equivalent)
R.W. Knudsen Organic Beet Juice 500 mL* 12.54 mmol / ~777 mg Independent lab paper (500 mL basis) $9.99 32 oz bottle (≈$5.27 per 500 mL) ≈$0.68 (per 500 mL equivalent)
Beet It Beet Juice (bottle) 500 mL* 7.55 mmol / ~469 mg Independent lab paper (500 mL basis) $49.99 case 12×250 mL (=$4.17/250 mL ≈ $8.34 per 500 mL) ≈$1.78 (per 500 mL equivalent)
Pomona Organic Beet Juice (bottle) 500 mL* 7.11 mmol / ~441 mg Independent lab paper (500 mL basis) $49.99 12×8.4 oz (≈$4.17/250 mL ≈ $8.34 per 500 mL) ≈$1.89 (per 500 mL equivalent)
Biotta Beet Juice 500 mL 4.81 mmol / ~299 mg Independent lab paper (500 mL basis) $7.79 500 mL bottle example price ≈$2.61
Love Beets Beet Juice 500 mL* 3.35 mmol / ~208 mg Independent lab paper (500 mL basis) $4.99–$5.99 10 fl oz (296 mL) bottle; price shown per bottle (not 500 mL) —
  • For bulk juices, the paper quantified nitrate per 500 mL. I normalized “cost per 500 mL equivalent” using the retailer’s bottle price/volume (shown in Price basis).

Quick takeaways

  • Among standardized shots, Amacx and Umara provide ~500 mg nitrate per shot at the lowest cost per 100 mg in their regions (≈€0.50 and ≈€0.48/100 mg respectively), with 6d close behind (≈€0.78/100 mg).
  • In the U.S., Beet It Sport Nitrate 400 is widely available and consistent (~400 mg/shot) at ≈$0.84 per 100 mg. Red Ace doses lower (~171 mg/shot), making cost per nitrate comparatively high.
  • For economy at higher volumes, plain Lakewood or R.W. Knudsen beet juice deliver the best $/nitrate when you’re ok drinking larger volumes (calculated per 500 mL).
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#83

Getting nitrate in a toothpaste like this is a very expensive way to get more nitrate, not only because the nitrate is only going to be a small part of the toothpaste (and people don’t use a ton of toothpaste) but also because some of the benefits of nitrate are derived from swollowing it rather than exposing the oral cavity to it directly and you’re not going to be swallowing the toothpaste.

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#84

NOlevels2
NOlevels2882×1176 89 KB

Source: https://x.com/robertlufkinmd/status/1984667929783210063?s=20

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