Hoffman Effect

Methionine addiction in cancer cells is termed the Hoffman effect in recognition of Dr. Robert M. Hoffman's foundational discovery of this metabolic hallmark nearly five decades ago. His research revealed that cancer cells universally depend on exogenous methionine due to their aberrant overuse of this amino acid for excessive transmethylation reactions. These processes are critical for epigenetic regulation and malignancy.

Key Features of the Hoffman Effect:

Excess Transmethylation: Cancer cells consume methionine at elevated rates to fuel abnormal methylation of targets like histone H3 lysine residues, driving oncogenic gene expression.

Malignancy Link: This addiction correlates tightly with tumor aggressiveness, as reverting cancer cells to methionine independence reduces histone hypermethylation and tumorigenic potential.

Distinct from Normal Cells: Unlike healthy cells, cancers cannot thrive on homocysteine (a methionine precursor) despite retaining methionine synthesis capacity, highlighting their unique metabolic dependency.

The Hoffman effect is similar to the Warburg effect in glucose metabolism; both are metabolic abnormalities in cancer cells, but it specifically identifies methionine as a potential therapeutic target.

Highest Food Sources of Methionine

All amounts below are found in foods per 100gm serving:

Egg (whole, dried) 1475mg

Spirulina (dried) 1150 mg

Parmesan cheese (grated) 1015mg

Brazil Nuts (dried, raw) 1008mg

Chicken Breast (cooked) 925mg

Lamb (shoulder, braised) 912mg

Beef (braised) 907mg

Tuna (Bluefin, cooked) 885mg

Sesame seeds (dried) 880mg

Turkey (roasted) 865mg

Goats Cheese (hard) 815mg

Trout (cooked) 785mg

Salmon (red, raw) 780mg

Tuna (canned, drained) 755mg

Pepitas (roasted) 740mg

Liver (chicken, cooked) 608mg

Gelatin (powder) 605mg

Nuts contain considerable amounts of methionine:

Walnuts – ~250 mg

Almonds – ~150 mg

Cashews – ~210 mg

Pecans – ~270 mg

Hazelnuts – ~180 mg

Macadamia nuts – ~200 mg

Pistachios – ~370 mg

Peanuts (technically a legume) – ~320 mg

Lowest Food Sources of Methionine

Apples – ~1 mg

Bananas – ~8 mg

Oranges – ~7 mg

Grapes – ~6 mg

Strawberries – ~9 mg

Blueberries – ~6 mg

Watermelon – ~5 mg

Tomatoes – ~7 mg

Cucumbers – ~5 mg

Lettuce – ~6 mg

White rice (cooked) – ~16 mg

Cornmeal – ~19 mg

Oats (cooked) – ~18 mg

Pasta (cooked, unenriched) – ~22 mg

White bread – ~25 mg

Tofu (soft) – ~28 mg

Potatoes (boiled) – ~12 mg

Sweet potatoes – ~8 mg

Mushrooms – ~14 mg

Carrots – ~7 mg

Avocado – ~38 mg

🌱Low-methionine meal plan

Synergy of Combining Methionine Restriction and Chemotherapy: The Disruptive Next Generation of Cancer Treatment {ref}

Plummer, J. D., & Johnson, J. E. (2022). Intermittent methionine restriction reduces IGF-1 levels and produces similar healthspan benefits to continuous methionine restriction. Aging Cell, 21, e13629. https://doi.org/10.1111/acel.13629