In 1951, a nutrition researcher gave rats every vitamin science knew about and then dropped them into cold water. They quit in thirteen minutes. The rats that had been fed liver were still swimming two hours later. That experiment is the best answer I have to the question patients ask me constantly: why don’t you recommend synthetic vitamins?
The experiment
Benjamin Ershoff raised three groups of rats from weaning. The first group ate a purified diet containing all eleven vitamins known at the time. The second group ate the same diet plus the entire B-complex on top. The third group ate the same diet with 10 percent dried liver mixed in.
In warm water, every rat swam for two hours. In water at 20°C, the groups separated. The vitamin rats lasted 13.3 minutes. The extra-B-vitamin rats lasted 13.4 minutes, so every B vitamin known bought them six seconds. The liver rats swam 63, 83 and 87 minutes on average across the liver-fed cohorts, and nine of the twelve were still going when Ershoff stopped the test at two hours.
He called whatever was in the liver the “anti-fatigue factor.” Seventy-five years later, nobody has isolated it.
The iron objection, and why it makes the point
The usual critique is that the purified diet was low in iron and liver simply corrected that. Maybe iron was part of it. But nobody ever reproduced the result by adding iron to the vitamin list, and the factor was never found. I think that is because it is not a factor at all. It is synergy: iron with the copper that lets you use it, B12 and folate in the forms the body recognizes, CoQ10, heme, and cofactors that still do not have names, arriving together in the ratios nature worked out long before we started counting.
The best science of 1951 built a “complete” diet and left out what it did not understand. We are still doing that. A single isolated vitamin, dosed by the milligram, is a guess about which nutrient you need, how much of it, and what it needs alongside it to work.
What happens when the guess is wrong
I recently wrote about the other side of this coin: megadosed niacin and NAD boosters leave behind a metabolite called 4PY that inflames the artery wall. In the 2024 Nature Medicine study from the Cleveland Clinic, people with the highest 4PY levels had roughly double the rate of heart attack, stroke and death over three years. Same lesson from the other direction. Isolate a nutrient and you get the nutrient plus whatever the body does with the excess. Eat the organ and the body decides what to absorb and in what proportion.
We know the copper-to-zinc ratio. We do not know copper to boron. We are still copying nature, and we have not finished reading the manual.
Why the only supplements I recommend are whole food supplements
This is why my rule with patients is fewer bottles, from food. Whole food supplements in my practice mean freeze-dried organs in place of a synthetic B-complex, an iron pill and a CoQ10 capsule; freeze-dried wild salmon roe for methylated B vitamins, omega-3s and choline in their natural forms and ratios rather than three separate bottles; and shilajit resin for the trace minerals no label has ever managed to itemize. Three things, and all of what the 1951 rats were missing, including the parts nobody has named yet.
It is the same logic behind my view on fish oil: the atrial fibrillation signal in the trials came from high-dose purified omega-3 preparations, not from eating fish. Isolate a molecule, concentrate it, and you get effects the whole food never produced.
I recently described an 82-year-old patient whose persistent atrial fibrillation converted to normal rhythm on a root-cause plan, without an ablation or a cardioversion. One piece of that plan was replacing his shelf of synthetic supplements with a handful of whole-food ones. Fewer pills, not more.
The bottom line
If you are still taking a synthetic multivitamin or a B-complex, this is a good week to ask why. What is in your cabinet: the list, or the liver?
If you would like a second opinion on your own supplement list and heart risk, I offer telehealth second-opinion consults. More about my background at AndrewRudinMD.com, and more heart-rhythm articles at BestHeartBeat.com.
Sources
Ershoff BH. Beneficial effects of liver feeding on swimming capacity of rats in cold water. Proceedings of the Society for Experimental Biology and Medicine 1951;77:488–491.
Ferrell M, Wang Z, Anderson JT, et al. A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk. Nature Medicine 2024;30:424–434.