A. What the recent papers actually show (short)

1. Multiple groups have used stable-isotope (¹³C) tracer infusion in humans and rodents to ask which carbon atoms in tumors come from which nutrients. Those studies show some aggressive tumors rapidly incorporate glucose (or fructose) carbon into tricarboxylic-acid (TCA) intermediates and downstream products — i.e., tumors can channel sugar carbon into the TCA cycle. This metabolic labeling is a tracer observation, not proof that ¹³C naturally causes cancer.

2. Work (including recent papers/press from MD Anderson and others) shows that combined glucose+fructose metabolism can activate pathways (e.g., via SORD producing sorbitol) that promote colorectal cancer progression/metastasis in preclinical models; the authors used ¹³C tracers to track whether fructose vs glucose supplies the carbon in those products. Again: tracer → mechanism insight.

3. Separate literature (Cleveland Clinic, others) has reported associations between circulating erythritol / some sugar-alcohols and thrombosis / cardiovascular risk in humans; those findings are about sugar-alcohol biology and risk, not isotopic ¹³C causation.

---

B. Key conceptual point: tracer labeling ≠ causal effect of natural ¹³C

Tracer logic: When researchers give cells or patients ¹³C-labeled glucose (a tracer), they are deliberately increasing the fraction of ¹³C in that glucose so mass spectrometry/NMR can follow where those carbons go. Seeing ¹³C show up in TCA intermediates means the tumor is using the supplied sugar carbon — exactly what you’d expect. It does not mean that the tiny natural differences in ¹³C abundance between diets cause cancer.

Natural abundance is tiny and only modestly different across diets. Natural ¹³C abundance is ~1.1% of carbon, and C3 vs C4 plants differ in δ¹³C by on the order of ~10‰ (permil), which is easily measurable with isotope geochemistry but corresponds to only small relative changes in fractional ¹³C — not orders-of-magnitude changes that would massively alter chemistry. In short: switching between C3 and C4 plant diets changes δ¹³C signals that are geochemically useful, but the absolute change in ¹³C fraction is small.

Kinetic isotope effects (KIEs) are typically small for ¹³C. Enzymatic reaction rates sometimes differ slightly with heavier isotopes (¹³C vs ¹²C) — that’s the kinetic isotope effect — but for carbon these effects are usually modest (fractions of a percent to a few percent) unless the chemical step directly breaks a C–H or C–C bond in a way that strongly discriminates. A tiny KIE is unlikely on its own to turn a healthy metabolic state into cancer. (If the claim is that modest KIEs accumulate biologically and trigger malignant transformation, that would require new, very strong evidence.)

So: seeing ¹³C label in tumor metabolites is expected when you feed labeled sugar; it’s excellent evidence about nutrient routing, but not evidence that natural dietary ¹³C causes cancer.

---

C. How to test your hypothesis (practical experiments that would be convincing)

If you propose that higher ¹³C in cellular metabolites (from C4 diets or enriched ¹³C sugar) causes cancer or accelerates it, here are the direct, testable experiments that would be needed:

1. Controlled long-term diet animal study (C3 vs C4):

Two groups of genetically similar rodents fed isocaloric diets identical except for carbon isotope signature (C3-based vs C4-based carbohydrate). Monitor cancer incidence, latency, and progression in spontaneous, carcinogen-induced, and genetically susceptible models.

Measure δ¹³C and absolute ¹³C fraction in serum and tissues over time and correlate with histopathology.

Why convincing: shows whether natural diet-level δ¹³C differences change cancer risk.

2. Enriched-¹³C feeding experiment (dose response):

Feed animals increasing levels of ¹³C-enriched glucose (well above natural variation) while keeping other variables constant and assess whether higher ¹³C burden alone promotes tumor initiation or accelerates progression.

Use appropriate controls to rule out isotope-label side effects (osmolarity, caloric differences). Why convincing: if enrichment at realistic magnitudes causes cancer, that’s strong causal evidence.

3. Cell-level mechanistic tests:

Culture normal and transformed cells on media with identical chemistry but different ¹³C/^12C ratios. Measure growth rate, ROS, mitochondrial function, genomic instability, epigenetic marks, and signaling pathways.

Use highly sensitive assays for KIEs on enzymes hypothesized to be rate-limiting (measure enzymatic rates with ¹²C vs ¹³C substrates). Why convincing: would identify plausible molecular mechanisms linking ¹³C substitution to malignant phenotypes.

4. Epidemiology with isotope markers:

Use existing human cohorts that have measured δ¹³C in blood/tissues and correlate individual δ¹³C with later cancer incidence, controlling for confounders (total sugar intake, obesity, smoking, socioeconomic factors).

Why convincing: population association consistent with mechanistic/animal data strengthens the claim.

5. Alternative explanations to rule out:

Diets rich in C4 sugars (e.g., corn syrup) correlate with higher caloric intake, obesity, and metabolic disease — all cancer risk factors. Any diet-cancer association must separate isotope effects from these confounders.

---

Quick summary / bottom line

The recent tracer studies you referenced show tumors use sugar carbon (hence show ¹³C label when labeled sugar is supplied). That’s an important metabolic insight.

That tracer signal does not prove that natural dietary ¹³C or the small δ¹³C difference between C3 and C4 plants causes cancer. The absolute natural differences are small and kinetic isotope effects for ¹³C are usually tiny.

Your hypothesis — that raised ¹³C in intermediates drives malignancy — is testable and would be revolutionary if true. It would require well-controlled animal, cellular, and epidemiologic evidence (preferably with enriched-¹³C dosing experiments and mechanistic enzyme studies) to convince the field.

---

Useful papers / links to start (the most relevant)

UT Southwestern / Cancer Discovery (2025): tumors that channel glucose carbon into the TCA predict early metastasis.

Nature Metabolism / MD Anderson–linked paper (2025): glucose+fructose feed sorbitol pathway and promote colorectal metastasis (used ¹³C tracers to show carbon source).

Science Advances (2022): in vivo ¹³C-glucose infusion labels tumor TCA cycle in mice and humans (isotope-tracing methodology).

Cleveland Clinic erythritol studies (2023–2024): erythritol linked to thrombosis signals (relevant to sugar-alcohol disease associations).

Reviews on natural δ¹³C differences between C3/C4 plants and isotope basics.

Hi Dr. Adewuyi, thanks for feed back. Yes, I already knew what you put forth here that 13c has been used as a tracer. But I reason 13c is not just reacting like 12c. Other scientists think i am wrong. I would like to experiment to test my idea of 13c. It has been hard to get resources for such. I realize such experiments if true would be quite important. If I am not able to do some of these less hope some one can.

Dr Adewuyi, although I appreciate what you are communicating, I disagree with a lot of it. I disagree mainly because you assume 13c will react under enzymes very similar to 12c. Such similarity is basis for 'tracer' reasoning of most scientists. I have unique idea that under enzymatic conditions 13c would react differently. There is data to support my idea, hence my idea is a theory. Even in this recent MD Anderson ecperiment with 13c label fructose and glucose, they are surprised as 13c manifest different effects. I realize experiments are needed to convince most scientists. But I lack lab and resources for such.

I (Reginald B. Little, RBL) am fully aware of how to test my theory and get very quick results. But I lack laboratory for such. If someone is interested in collaborating, then please contact me.

I (RBL) propose the following to give some quick rough data to determine if 13C stable isotope or carbon 13 is causing cancer and accelerating cancer as a follow up of the research at MD Anderson Cancer Center:

I notice that prior measurements performed in-vivo studies on the mice giving them d-fructose and d-glucose and saw the mix of d-fructose and d-glucose caused cancer to metathesize and become more malignant.  In these experiments according to Sigma-Aldrich the d-glucose and d-fructose were both derived from corn (C4) plant. This supports my theory of 13C causing and accelerating cancer as corn is a C4 plant and the fructose and glucose from corn are more enriched in 13C isotope that fructose and glucose from C3 plants like healthier fruits and veggies. So eating corn products from my prior theory is equivalent to daily infusing of 13C into the bodies of humans in equivalence to infusing 13C via corn glucose and fructose into the mice from this experiment with similar acceleration of cancer in the human host and faster metathesis of the cancer in the human to explain accelerating cancer in humans from diet and the accelerated metathesis in humans from sugary beverages by 13C isotope rather than fructose itself. But to ascertain this a control is needed of measuring the metathesis of the cancer in diet of lower 13C in the fructose and glucose. Therefore, I recommend:

1) I am interested in a similar experiment to compare with the published MD Anderson Cancer study involving in-vivo experiment but feeding the mice d-fructose and d-glucose from a C-3 plant.  I am wondering if the C3 plant having less than 13C would affect the metathesis (I think it may decrease the metathesis relative to the C4 glucose and C4 fructose, which have more 13C isotopes!).

2) A second in-vivo experiment would involve feeding the mice the isotope heavily labeled 13C6 fructose and 13C6 glucose (where all 6 carbons in the sugars are 13C) to see if the greater content of 13C accelerated the malignancy and metastasis.

It could also be that the heavy labeling by 13C kills the cancer. I think it may accelerate the cancer but under some conditions I propose the 13C can kill the cancer and give new basis for selective treatment.

For instance, I predict the heavily enriched 13C in cancer in vivo in patients afford irradiating the patient with anti-neutrinos by shielding the patient and placing near a nuclear reactor. The heavy shielding protects the patient from the deadly radiation, but the neutrinos pass straight thru the shielding. But by my prediction whereas the neutrinos do not interact with the shielding, the neutrinos interact with the 13C in the cancer cells in the patient to disrupt the cancer and possibly kill the cancer throughout the patients' bodies.

I know many people will be negative and receive my theory with harsh criticism, but I continue thinking and creating so long as I find virtue of possibly helping humanity and reducing human suffering and healing (I am true) in love and compassion for humanity. - Reginald B. Little