Nicotinamide adenine dinucleotide (NAD+) induces an intermediate state of naivety in human embryonic stem cells (hESCs) characterized by a shift from glycolytic to oxidative metabolism, increased self‐renewal, and epigenetic alterations. Conversely, inhibition of the malate aspartate shuttle (MAS), which recycles NAD+, causes a dramatic loss of oxidative metabolism and pluripotency marker expression.