Meet Mark

Let me introduce myself. My name is Mark Sisson. I’m 63 years young. I live and work in Malibu, California. In a past life I was a professional marathoner and triathlete. Now my life goal is to help 100 million people get healthy. I started this blog in 2006 to empower people to take full responsibility for their own health and enjoyment of life by investigating, discussing, and critically rethinking everything we’ve assumed to be true about health and wellness...

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Is Long-Term Ketosis Necessary—Or Even Desirable?

A good six weeks of ketosis puts in place all the metabolic machinery for lasting adaptation (those extra mitochondria don’t evaporate if/when you return to traditional healthy low-carb/ Primal eating).

But what about the other end of the issue? How long is too long?  One thing led to another, and this paper got me thinking: once we “go into ketosis,” how long should we stay? If some is good, is more better? Is there a point where the benefits slow and the downsides accrue?

Why Ketosis Can Be a Healthy State To Maintain

We absolutely know that ketones, particularly BHB, do lots of cool things for us. There’s the NLRP3 inflammasome inhibition, for one. There’s also the effect it has on brain health and function, particularly in the context of neurodegenerative diseases and other brain conditions.

Brain Aging:

  • Whether it’s severe hypoglycemia in a live rat or direct glucose deprivation of cortical cells in a petri dish, the addition of BHB protects against neuronal death, preserves energy levels, and lowers reactive oxygen species.
  • In an animal model of Cockayne syndrome, a condition characterized by premature aging, short stature, and early death (about age 10 in most human children with it), increasing BHB through ketosis postpones brain aging.

Brain Disorders:

  • Ketogenic diets are classic therapies for epilepsy, with BHB being the most important ketone for preventing seizures. The degree of seizure control tracks almost lockstep with rising BHB levels.
  • There’s also evidence that patients with bipolar — a disorder sharing certain neurobiological pathways and effective therapies with epilepsy — can also benefit from ketosis. Recent case studies show complete remission of symptoms in two patients as long as they adhered to their diets (which were fairly Primal-friendly, for what it’s worth).
  • Parkinson’s disease patients who adhered to a ketogenic diet saw improvements in their Unified Parkinson’s Disease Rating Scale scores.

Brain Function:

  • Type 1 diabetics who experience reduced cognitive function because of low blood sugar see those deficits erased by increasing BHB through dietary medium chain triglycerides (the same fats found in coconut oil).
  • In memory impaired adults, some with Alzheimer’s, BHB improved cognition. Scores improved in (rough) parallel with rising ketones.
  • A ketone-elevating agent (purified medium chain triglycerides) improved cognition in patients with mild to moderate Alzheimer’s.
  • A very low-carb diet improved memory in older adults. Again, ketones tracked with improvements.

Mitochondrial levels of the endogenous antioxidant glutathione increase on a ketogenic diet; this is likely a major reason for many of its beneficial effects.

It’s quite clear why constant ketosis is attractive to people who read about (and experience for themselves) the benefits of BHB and ketosis in general: There don’t appear to be many downsides. Improved brain health? Increased antioxidant capacity? Inhibition of an inflammatory set of genes involved in the worst kinds of degenerative diseases? What’s not to love? Why wouldn’t someone remain indefinitely ketogenic?

Ketosis also activates the NRF2 pathway — a set of genes that regulate the body’s detoxification, antioxidant, and stress response systems — by initially increasing systemic oxidative stress. If that sounds a bit like hormesis, you’d be right. Ketosis, at least in the early stages, exerts some of its beneficial effects via hormetic stress. Various other stressors also activate NRF2, like plant polyphenols from foods like blueberries and green tea, potent spices like turmeric, intense exercise, and intermittent fasting. These all improve our health by triggering our stress resistance pathways and making us grow stronger for it, but they can also be taken to an extreme and become negative stressors.

Should You Stay In Constant Ketosis?

If you’ve got a legitimate health condition that responds well to ketosis, all bets are off. There’s evidence that people can thrive on good ketogenic diets for at least five years without incurring any serious side effects. For controlling epilepsy, there’s nothing better than a strict ketogenic diet maintained long term to quell the overexcited brain. For any of the neurodegenerative diseases, like Alzheimer’s or Parkinson’s, ketogenic diets look very promising and are worth trying. It even looks promising for bipolar disorder. If you’ve got a problem that ketosis helps or fixes, go for it. It’s helping you, and there’s no mistaking that.

Indefinite ketosis is unnecessary and perhaps even undesirable for most healthy people, and that occasional, even regular dips into ketosis (through fasting, very low-carb cycles, intense exercise) are preferable and sufficient. That way, you get the benefits of cyclical infusions of BHB and other ketones without running afoul of any potential unforeseen negative effects.

Plus, cycling your ketosis means you can eat berries and stone fruits when in season, and enjoy those otherworldly-delicious purple sweet potatoes without worrying. Personally, I like food too much to go full-on, indefinite keto. You may not, and that’s okay.

If you’re thriving on a ketogenic diet, and have been for some time, keep it up. No one can take that away from you, and the studies indicate it should be safe. I certainly know people who have lived a keto lifestyle for years without issue.

But if you don’t have to remain in ketosis to resolve or stave off a health condition, if you’re just doing it to do it or for yet-to-be-realized benefits, consider rethinking your stance. And if ketosis doesn’t agree with your health or your personal performance goals, then don’t consider it an obligation.

Because the goal of keto isn’t keto itself. It’s the metabolic reset that confers a potent and enduring flexibility. It’s the recalibration of inflammatory patterns along with other aforementioned benefits. How we customize our keto (or more traditional Primal) approaches should ultimately serve optimal personal health, not technically-minded dogma.