Do 4x4 intervals protect the hippocampus? 6 of 8 disagree

Does interval training like the Norwegian 4x4 protect the hippocampus?

The claim checked: Norwegian 4x4 intervals protect the hippocampus better than moderate exercise Hear it at 1:45:34

What do the studies say?

Conflicting

Two trials found interval training beat moderate exercise on memory, among them the trial described on tape. Six found no edge for high intensity on the size or chemistry of the hippocampus, the brain area for memory, or on thinking. One of them, the Generation 100 trial, followed older adults for 5 years and found no larger brain volumes.

Computed from 8 studies that test this point, each judged by two readers, in full. Sources land on both sides. 2 more studies are waiting for a full read and do not count yet.

The study behind the claim tested something else. See what it tested

What was said on the podcast?

“And they maintained that benefit for 5 years after the six-month intervention. So they worked really hard um for 6 months, but that that benefit was maintained for for a really long period of time.”

Tommy Wood, a guest on Huberman Lab · Accelerate Learning & Increase Cognitive Capacity | Dr. Tommy Wood · 1:45:34 on YouTube

The study behind the claim The retelling overstates it

What did the study actually test?

On tape: a recent trial of low, zone 2 and Norwegian 4x4 training, three times a week for 6 months, with a 5-year follow-up. This trial matches. Only the learning gain was followed to 5 years from the start; the MRI stopped at 12 months, and the left hippocampus shrank in every group. Long-Term Improvement in Hippocampal-Dependent Learning Ability in Healthy, Aged Individuals Following High Intensity Interval Training. Aging Dis, 2024. Randomized trial of low-intensity, moderate continuous and 4x4 high-intensity interval training, 72 sessions over 6 months, followed up to 5 years from the start, 151 healthy adults aged 65 to 85 with no cognitive deficits who completed all sessions.

What was saidWhat the study did

What was given Matches Norwegian 4x4 intervals, three times a week for 6 months 4x4 minutes at 85 to 95% of peak heart rate, 72 sessions over 6 months

Compared with Matches Zone 2 treadmill work Moderate continuous treadmill training

What was measured Matches Much better hippocampal function and kept hippocampal structure, for 5 years Paired associative learning to 5 years from the start; MRI volume to 12 months

Who took part Matches Older adults 151 healthy adults aged 65 to 85

What it found

“After 6 months, only the HIIT group displayed significant improvement in hippocampal function, as measured by paired associative learning (PAL).”

PMID 39012673

How the authors extend it

“Importantly, improvement was retained for at least 5 years following initiation of HIIT, suggesting that the changes seen in hippocampal volume and connectivity underpin this long-term maintenance.”

PMID 39012673

Not stated in the text we read. Two readers agreed on the label, and the paper was read in full.

The point checked Conflicting

In older adults, high-intensity interval training such as the Norwegian 4x4 improves hippocampal function or structure more than moderate exercise

Agree 2

controlled trial · 2024 · cited on tape

“At each testing period following the conclusion of the exercise trial, the HIIT group performed significantly better than both the LIT and MIT groups.”

Long-Term Improvement in Hippocampal-Dependent Learning Ability in Healthy, Aged Individuals Following High Intensity Interval Training. Aging Dis
Who: Healthy, cognitively normal adults aged 65-85 in Queensland, Australia (mean age ~72), randomized to low-intensity (LIT), moderate-intensity (MIT) or HIIT; MRI on a subset
PMID 39012673

other primary study · 2020

“Pairwise comparisons revealed that HIIT induced better memory performance than MCT (Cohen’s d = 1.2, p = .003) and CON (Cohen’s d = 1.1, p = .004) but MCT and CON were not significantly different from each other (p = .85).”

The effects of aerobic exercise intensity on memory in older adults. Appl Physiol Nutr Metab
Who: Sedentary but otherwise healthy community-dwelling adults over 60 in Hamilton, Canada (61% female, mean age 72, range 60-88)
PMID 31665610

Partly agree 0

None.

Disagree 6

controlled trial · 2021

“Contrary to our hypotheses, 5 years of HIIT or MICT intervention did not lead to larger brain volumes or reduced atrophy at any time point during the study compared to the control group.”

Effect of 5 Years of Exercise Intervention at Different Intensities on Brain Structure in Older Adults from the General Population: A Generation 100 Substudy. Clin Interv Aging
Who: 105 healthy older adults aged 70-77 from the general population of Trondheim (Generation 100 brain MRI substudy): 48 control, 24 MICT, 33 HIIT
PMID 34408409

controlled trial · 2026

“Overall, although HIIT has been shown to positively affect various aspects of physical health [ 28 ], we found no evidence that it benefits brain health in older adults in the long term.”

Long-Term Effects of a 5-Year Randomized Controlled Exercise Trial on Brain Volumes and Cognitive Function in Older Adults: A 4-Year Post-Intervention Follow-Up Study. Sports Med
Who: Healthy, physically fit older adults from Trondheim, Norway (mean age ~73 at baseline, ~81 at 9 years) in the Generation 100 brain MRI substudy, randomized 2:1:1 to control (national activity guidelines), MICT or HIIT
PMID 41999477

controlled trial · 2016

“In line with this interpretation, visual inspection of the volumetric changes suggested increased volumes in the LI group as compared to stable volumes in the HI group, though the difference was not statistically reliable.”

Changes in fitness are associated with changes in hippocampal microstructure and hippocampal volume among older adults. Neuroimage
Who: Healthy sedentary adults aged 59-74 (mean 66.0, 20 men) in Berlin
PMID 26584869

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controlled trial · 2021

“When examining the group-level data, we found no effect of either the high- or moderate-intensity exercise interventions on cognitive performance.”

High-intensity exercise and cognitive function in cognitively normal older adults: a pilot randomised clinical trial. Alzheimers Res Ther
Who: Cognitively normal, community-dwelling older adults in Western Australia (mean age ~69, highly educated, Caucasian), randomized to high-intensity, moderate-intensity or inactive control
PMID 33522961

controlled trial · 2023

“Moreover, higher exercise intensity, irrespective of group, was associated with lower Cho/Cr in the same part of the hippocampus.”

Hippocampal neurochemicals are associated with exercise group and intensity, psychological health, and general cognition in older adults. Geroscience
Who: Healthy older adults from the general population of Trondheim, Norway (Generation 100 MRI substudy, mean age ~75 at 3 years); supervised exercise group (HIIT and MICT combined) vs active control following national activity guidelines
PMID 36626020

pooled analysis · 2025

“The meta-analysis results indicated that across all time spans, exercise modalities, intensity levels, elderly groups, left/right hippocampus subgroups, and durations, exercise did not exert a significant effect on hippocampal volume ( P > .05).”

The impact of exercise intervention on hippocampal volume in the elderly: A meta-analysis. Medicine (Baltimore)
Who: RCTs in adults aged 60-80, 5 in healthy older adults and 7 in people with MCI, Alzheimer disease or dementia
PMID 41431091