Summary: A small pilot study suggests that adults with mild cognitive impairment may experience improved brain function and memory after switching to a high-fat, low-carbohydrate diet.
Source: Johns Hopkins Medicine
In a small pilot trial involving older adults with mild cognitive changes that can precede Alzheimer’s disease, researchers at Johns Hopkins Medicine report that a high-fat, low-carbohydrate diet was associated with measurable improvements in memory and some aspects of brain function.
Recruiting participants willing to follow a restrictive eating plan for 12 weeks — and partners willing to help maintain adherence — proved difficult. Still, among those who followed a modified Atkins diet (very low carbohydrates with increased fat), researchers observed modest but statistically meaningful improvements on standardized memory tests compared with participants assigned to a low-fat, NIA-style diet.
The short-term results, published in the April issue of the Journal of Alzheimer’s Disease, do not prove that the modified Atkins diet will prevent progression from mild cognitive impairment (MCI) to Alzheimer’s disease or other dementias. However, the findings are promising enough to justify larger, longer-term trials exploring dietary approaches to support brain health.
“Our initial results indicate we may not have to be as strict about carbohydrate restriction as we first assumed. A milder diet or the addition of a ketone supplement could produce similar benefits and be easier for people to follow,” says Jason Brandt, Ph.D., professor of psychiatry, behavioral sciences and neurology at Johns Hopkins University School of Medicine.
“If these early findings are confirmed, dietary strategies to slow cognitive decline in early-stage dementia would be an important breakthrough — something more than the hundreds of experimental drugs tested in clinical trials so far.”
Brandt and colleagues explain that the brain normally relies on glucose — produced from carbohydrates — as its primary fuel. Evidence from multiple studies shows that in early Alzheimer’s disease the brain’s ability to use glucose efficiently can be impaired; some researchers describe this metabolic dysfunction as similar to diabetes in the brain. Ketones, which are produced during the breakdown of fats, can provide an alternative energy source for the brain when glucose is scarce or poorly metabolized.
Previous brain imaging research indicates that ketones are taken up and used by brain tissue in both healthy people and those with mild cognitive impairment. A ketogenic or very low-carbohydrate, high-fat diet shifts the body’s metabolism to produce ketone bodies, which the brain can then use for energy instead of relying on carbohydrates.
In this trial, the team tested whether forcing the brain to use ketones — by using a modified Atkins diet (MAD) — could benefit people with MCI, a condition often considered a possible precursor to Alzheimer’s disease.
After 2.5 years of recruitment, 27 eligible participants enrolled in the 12-week randomized study. Some participants dropped out; 14 completed the full protocol. The average age of completers was 71. Half were women and all but one were white. Each participant enrolled with a study partner, typically a spouse, who agreed to help implement the assigned diet for the full 12 weeks.
Nine participants were randomized to the modified Atkins diet, instructed to limit carbohydrates to 20 grams per day or less with no calorie restriction, while five participants followed a National Institute on Aging (NIA) diet similar to the Mediterranean pattern, emphasizing fruits, vegetables, low- or nonfat dairy, whole grains and lean proteins without restricting carbohydrates.
Food diaries and periodic urine testing tracked carbohydrate intake and ketone production. Participants assigned to MAD reduced their carbohydrate intake from a baseline average of about 158 grams per day to roughly 38.5 grams by week six, later rising to an average of 53 grams by week 12 — short of the 20-gram target but still a substantial reduction. Participants on the NIA diet continued to consume well over 100 grams of carbohydrates daily. More than half of those on the modified Atkins diet produced at least trace urinary ketones by six weeks; none of the control group had detectable ketones.
Participants completed baseline assessments including the Montreal Cognitive Assessment, the Mini-Mental State Examination and the Clinical Dementia Rating Scale, and they were given a brief battery of neuropsychological memory tests at baseline, six weeks and 12 weeks. The researchers observed the largest memory improvements at six weeks — the time point that coincided with the lowest carbohydrate intake and the highest ketone levels.
On tests of delayed recall, which measure the ability to remember information after a short delay, participants who adhered to the modified Atkins diet improved by roughly a couple of points on average (about a 15% improvement relative to the total score), while those on the control diet generally showed a small decline.
The investigators report that the biggest practical barrier was recruiting participants willing to make dramatic and sustained changes to their diets and finding study partners prepared to help enforce the regimens. In many cases, carbohydrate intake increased later in the study, suggesting the diet is difficult to maintain long term. “Many people prefer a pill to changing lifelong eating habits. Older adults often value familiar foods as one of their few daily pleasures and don’t want to give that up,” Brandt notes.
Because modest memory benefits appeared even among participants who were not fully strict with the diet, researchers believe a less restrictive high-fat, low-carb approach, or ketogenic supplements that raise ketone levels, could be practical alternatives worth testing. They also plan to investigate whether people with milder cognitive symptoms — who might be more able to manage their own food choices — would be more likely to adhere to and benefit from such dietary strategies.
Johns Hopkins previously developed a standardized modified Atkins diet in 2002 to treat certain seizure disorders; it remains an effective clinical option for that purpose.
According to the Alzheimer’s Association, an estimated 5.8 million Americans currently have Alzheimer’s disease, with projections indicating the number could grow substantially by mid-century.
Funding: This research was supported by the William and Ella Owens Medical Research Foundation, the BrightFocus Foundation and the National Center for Advancing Translational Sciences (UL1-TR001079). The Hass Avocado Board provided avocados to participants.
Conflicts of interest: Mackenzie Cervenka has consulted for Nutricia and Sage Therapeutics and has received grants from Nutricia and Vitaflo. Bobbie Henry-Barron has consulted for Nutricia and Vitaflo and has lectured for Nutricia.
Authors: Jason Brandt, Alison Buchholz, Bobbie Henry-Barron, Diane Vizthum, Dimitrios Avramopoulos and Mackenzie Cervenka, all affiliated with Johns Hopkins.
Source:
Johns Hopkins Medicine
Media Contacts:
Vanessa McMains – Johns Hopkins Medicine
Image Source:
Image credited to Johns Hopkins Medicine.
Original Research: Closed access. Title: “Preliminary Report on the Feasibility and Efficacy of the Modified Atkins Diet for Treatment of Mild Cognitive Impairment and Early Alzheimer’s Disease.” Journal of Alzheimer’s Disease. DOI: 10.3233/JAD-180995.
Abstract (summary):
Ketone bodies, produced during fat metabolism, can supply energy to the brain when glucose is limited or poorly metabolized, as occurs in Alzheimer’s disease. This phase I/II randomized trial tested whether a modified Atkins diet could induce ketone production in people with mild cognitive impairment or early Alzheimer’s disease and whether ketosis would affect memory and clinical outcomes. After recruitment, 27 patients were randomized to 12 weeks of either the modified Atkins diet or the National Institute on Aging (NIA) recommended diet; 9 in the MAD arm and 5 in the NIA arm completed the trial. Adherence was limited despite education and monitoring. Among MAD participants who produced trace urinary ketones, there was a statistically significant improvement in a composite memory score between baseline and week six, and participants also reported increased energy. Although the sample was small, the preliminary data suggest that even trace ketone generation may improve episodic memory and self-reported vitality in very early Alzheimer’s disease.