The Honest Fasting Guide: From 16:8 to 72-Hour Fasts

Once a year, in January, I go roughly three days without food. No snacks, nothing sneaked in. Just water, and a fairly grim stretch from somewhere around hour 36. They say it actually gets easier after the first 24 hours. I say they are liars.

The timing is deliberate. After what passes for a typical Irish Christmas - a few weeks that would make any nutritionist wince - January feels like the natural moment for a reset. The fast is my version of spring cleaning: clear out the cellular debris, give the immune system a boost at the time of year it most needs one, and start the year with something that actually requires a bit of discipline.

People hear "72-hour fast" and assume something has gone wrong. It hasn't. I've been doing it long enough to have genuine thoughts about what it does and doesn't achieve - and more importantly, what the research actually shows versus what tends to get written about it online.

This is that post.

What intermittent fasting actually is

Fasting covers a wide range of practices, so it's worth being clear before getting into the evidence.

The most common starting point is 16:8 - fasting for 16 hours, eating within an 8-hour window. A lot of people do this already without calling it anything. Stop eating after dinner at 7pm, skip breakfast, have lunch at 11am. That's roughly 16:8. Beyond that, 5:2 involves eating normally five days a week and restricting significantly on two non-consecutive days. OMAD (one meal a day) compresses all eating into a single sitting. Alternate-day fasting alternates normal eating days with full fast days.

Extended fasts - anything beyond 24 hours - sit in a different category. The physiology genuinely changes as the hours accumulate: glycogen stores deplete, the body transitions into ketosis, and a range of cellular processes accelerate that don't really engage during shorter windows. What I do in January falls here.

The protocols aren't interchangeable, and that distinction matters when you look at the evidence. Studies on 16:8 tell you something different from studies on 72-hour fasting cycles. Conflating them - as a lot of popular coverage does - leads to confusion.

What the evidence actually supports

The most comprehensive review of intermittent fasting research came from Rafael de Cabo and Mark Mattson, published in the New England Journal of Medicine in December 2019 (N Engl J Med 2019;381:2541-2551). It surveys the animal and human data, and it's worth understanding what it does and doesn't confirm.

On metabolic health, the evidence is solid. Intermittent fasting consistently improves insulin sensitivity, reduces fasting blood glucose, and improves markers associated with metabolic syndrome. Blood pressure and lipid profiles also improve in both animal studies and some human data.

On weight loss, the picture is more nuanced. The evidence suggests IF works roughly as well as continuous calorie restriction when total calories are matched. The advantage for most people isn't metabolic magic - it's that restricting eating windows tends to naturally reduce overall intake without constant tracking. Useful, but worth knowing that's the mechanism.

On longevity and disease risk, the human data is still developing. Animal studies are striking - caloric restriction extends lifespan across a remarkable range of species - but translating that to human outcomes with confidence requires more work than is being done.

Autophagy: the cellular spring clean

This is the part of the fasting conversation that most people come for, and also where the gap between popular explanation and the actual science is widest.

Autophagy - from the Greek for "self-eating" - is the process by which cells identify damaged proteins and dysfunctional organelles, break them down, and recycle the components. Yoshinori Ohsumi received the 2016 Nobel Prize in Physiology or Medicine for mapping the mechanisms behind this process, which is part of why it entered mainstream health conversation. The analogy that makes most sense to me is cellular housekeeping: clearing out biological debris before it accumulates and causes problems.

The January timing of my fast isn't accidental. After several weeks of eating and drinking way more than usual, the idea of giving the body a sustained opportunity to do that housekeeping makes intuitive sense. Whether you think of it as spring cleaning after Christmas, or just as hitting reset after a period of excess, the framing is fairly honest - and the mechanism behind it is actually real.

Fasting upregulates autophagy by suppressing mTOR (which promotes cell growth) and activating AMPK (an energy sensor that kicks in when cellular fuel drops). That signalling shift is well-established. Or so I'm told.

What's less settled is the precise timeline. The "autophagy kicks in at exactly X hours" claims you'll find online are largely extrapolated from animal and cell studies. Human data on the exact threshold is thin, and the research tools to measure autophagy in living humans accurately are still being refined. What we know is that it's not an on/off switch - more of a dimmer that turns up gradually. Significant activation appears to require somewhere around 24 to 48 hours, with individual variation. Whether 72 hours is meaningfully better than 48 is something the research doesn't confidently tell us yet. My reasoning is simply: if meaningful autophagy takes time to build, give it as much runway as possible.

The immune system angle

January is also peak season for colds, flu and every other thing circulating in Irish workplaces, schools and creches. Timing a practice that appears to support immune function at the start of the year is, to my mind, one of the more practical reasons to do an extended fast then rather than in, say, August.

The most interesting research on this comes from Valter Longo's group at USC, published in Cell Stem Cell in 2014. They found that prolonged fasting cycles caused a significant drop in white blood cells, followed by a regenerative response when eating resumed - with haematopoietic stem cells appearing to shift from dormant to self-renewing. The mechanism involved reduction of PKA and IGF-1.

The important caveat: the human component was a small Phase 1 trial in cancer patients fasting before chemotherapy. Longo has been careful about how broadly the findings generalise. What the research suggests is a plausible mechanism for immune regeneration through periodic extended fasting - not a confirmed protocol for everyday immune boosting.

I hold it as a reasonable hypothesis with a solid mechanistic basis, not as a certainty. But in January, when you're fresh off Christmas and surrounded by people coughing, "plausible mechanism for immune support" feels like a reasonably good reason to fast!

Fasting and NAD+

One of the downstream effects of fasting - captured in de Cabo and Mattson's review - is its influence on NAD+ levels and sirtuin activity. Sirtuins are proteins involved in regulating cellular stress response, metabolism and inflammation. They're NAD+-dependent: they need NAD+ as a cofactor to function. Fasting upregulates SIRT1 in particular, and part of the mechanism involves the liver's NAD+ salvage pathway becoming more active during fasting periods.

This is the thread connecting fasting practice to NAD+ precursor research. If sirtuins are key regulators of the fasting response, and sirtuins depend on NAD+, then supporting NAD+ levels through supplementation sits on the same biological pathway. I'll write a separate post later on the NMN-versus-NR question specifically - including the regulatory situation in Ireland and the EU, which matters practically if you're buying supplements here. 

The practical side

Electrolytes are the variable most people underestimate. When insulin drops and glycogen stores deplete, the kidneys shift mode and start excreting minerals faster than they retain them. The headaches and fatigue that hit on day two of an extended fast are usually not really hunger - they're sodium, potassium and magnesium depletion. Supplementing magnesium and adding a pinch of quality sea salt to water makes a significant difference to how you feel through that window. Don't overdo the sea salt though - a mistake I made at the start - that led me to do some porcelain based 'spring cleaning' of a different kind.

The refeeding phase matters more than most guides acknowledge. Coming out of a 72-hour fast with a heavy meal is a reliable way to feel awful. My own approach is bone broth for the first sitting - it's easily absorbed, provides gelatin and collagen that support the gut lining, and feels like the right way to ease the digestive system back into work. I use the Hunter and Gather one, but there's some great non freeze-dried ones available around Dublin if you look. After that, something fermented: a good sauerkraut introduces live bacteria back into a gut that's had a few days of complete rest. Whether that's an ideal microbiome reset or just a sensible transition, I find the combination works well and I'd rather start there than with a plate of pasta. Gut health after extended fasting is probably a post in its own right - there's more to say about it than fits here.

A note on who shouldn't fast, or who should check first: pregnancy (kind of obvious!), active eating disorder history, type 1 diabetes, anyone on medications that require food. Extended fasting is for stable, healthy conditions - not for periods of illness or high physical stress.

On muscle wastage

Worth mentioning honestly: I noticed that weekly 40-hour fasts, sustained over months, appear to have an effect on lean mass - (although being over 40 could also be the culprit - sigh!). A 2025 study in Nature Communications found that maximal leg strength was preserved across seven days of complete fasting despite lean mass decline - the body seems to prioritise functional capacity - but that's an isolated fast, not repeated weekly fasting alongside a training programme.

For anyone fasting regularly around exercise, adequate protein in the eating window - with attention to leucine-rich sources - is worth prioritising. Leucine is the key signal for muscle protein synthesis, and the evidence that it matters during calorie-restricted periods is solid. As a rough target, somewhere around 0.8 to 1.2 grams of protein per pound of bodyweight (about 1.8 to 2.6 g per kg) is the range usually cited for preserving muscle during calorie-restricted periods. Regular extended fasting probably involves a trade-off on muscle mass that's worth knowing about before committing to a protocol. Oh, but working out or doing Jiu Jitsu while fasted I found, upped weight loss and often helped me think better during rolls!

What I use around fasting

During extended fasts: water and electrolytes only. Coming out of the fast, bone broth and fermented foods before anything heavy - as above. In the eating window around regular fasting periods, NR as an NAD+ precursor makes sense as a natural complement given the sirtuin overlap. 

The bottom line

Intermittent fasting has solid evidence behind it, primarily around metabolic health and insulin sensitivity. The autophagy story is real but the timeline is less certain than it's typically presented. The immune angle has a plausible mechanistic basis that needs honest contextualisation. The NAD+/sirtuin connection puts fasting in a coherent place in the longevity conversation.

For most people, starting with 16:8 makes sense before pushing further. The protocols sit on a spectrum - you don't have to jump to 72 hours to get meaningful benefits.

And if you need a practical excuse to try an extended fast for the first time: January after Christmas is genuinely the most sensible time of the year for it. Your body will probably agree with you. And the pubs are dead anyway.