Abstract Health messages on low-energy diets for healthy weight loss are muddled and not working, and obesity rates are rising. Are there missing links? Accumulating evidence shows that humans have well developed 'self-addictive' appetite pathways to enhance the uptake of highly energy-dense food. Humans synthesize fewer co-factors and vitamins than other mammals and must ingest them. Both processes probably arose to maximize available energy for the developing, large association cortex of the human brain. The default phenotype resulting from consuming an 'addictive', westernized, highly refined, energy-dense, hypomicronutrient diet is 'malnutritive obesity' or 'malnubesity'. A relative lack of antioxidant (and other) co-factors contributes to inefficiently oxidized energy. This 'stress' leads to central fat deposition, disordered energy use by cell mitochondria, especially in muscle and liver, and malfunctioning immune, coagulation, endothelial, and other systems. The resultant problems appear to range from epigenetic reprogramming in utero to end organ damage of the metabolic syndrome and the immune failure of cancer. Treatment of 'malnubesity' may require: (1) understanding the drivers and mechanisms of addictions, (2) reprioritizing satiating, micronutrient-dense whole foods, (3) nonjudgmental general, psychological, and medical support for those at risk or affected by obesity; and (4) practical incentives/regulation for healthy food production and distribution.