Medium-chain fatty acids for the prevention or treatment of Alzheimer’s disease: a systematic review and meta-analysis

Abstract

Context In preclinical Alzheimer’s disease (AD), the brain gradually becomes insulin resistant. As a result, brain glucose utilization is compromised, causing a cellular energy deficit that leads to the accumulation of free radicals, which increases inflammation and damages neurons. When glucose utilization is impaired, ketone bodies offer an alternative energy source. Ketone bodies are synthesized from fats, obtained from either the diet or adipose tissue. Dietary medium-chain fatty acids (MCFAs), which are preferentially metabolized into ketone bodies, have the potential to supply the insulin-resistant brain with energy. Objective This systematic review and meta-analysis aims to review the effect of MCFA supplements on circulating ketone bodies and cognition in individuals with subjective cognitive decline, mild cognitive impairment, and AD. Data Sources A comprehensive search of electronic databases was performed on August 12, 2019, to retrieve all publications meeting the inclusion criteria. Alerts were then set to identify any publications after the search date up until January 31, 2021. Data Extraction Data were extracted by 2 authors and assessed by a third. In total, 410 publications were identified, of which 16 (n = 17 studies) met the inclusion criteria. Data Analysis All studies assessing change in levels of blood ketone bodies due to MCFA supplementation (n = 12) reported a significant increase. Cognition outcomes (measured in 13 studies), however, varied, ranging from no improvement (n = 4 studies) to improvement (n = 8 studies) or improvement only in apolipoprotein E allele 4 (APOE ε4) noncarriers (n = 2 studies). One study reported an increase in regional cerebral blood flow in APOE ε4 noncarriers and another reported an increase in energy metabolism in the brain. Conclusion MCFA supplementation increases circulating ketone body levels, resulting in increased brain energy metabolism. Further research is required to determine whether this MCFA-mediated increase in brain energy metabolism improves cognition. Systematic Review Registration PROSPERO registration number CRD42019146967.

Medium-Chain Triglycerides (MCTs) for the Symptomatic Treatment of Dementia-Related Diseases: A Systematic Review

“…Plasma levels in the control groups remained unchanged. Tis signifcant between-group efect was also confrmed in recent meta-analyses, with a mean diference between the intervention and control groups of 0.355-0.726 mmol/L ßHB (I 2 � 0%; p � 0.02) [63,64]. However, the plasma levels of ßHB remained below the ranges achieved with a ketogenic diet (>1 mmol/L) or administration of exogenous ketone esters (>3 mmol/L) [65][66][67].…”

The Effects of Medium Chain Triglyceride for Alzheimer’s Disease Related Cognitive Impairment: A Systematic Review and Meta-Analysis

“…This systematic review has its value in being one of the very few and most recent systematic reviews conducted on the impact of MCT in cognitive function in AD patients. The use of our keyword terms identified all studies included in previous systematic reviews [18,26], as well as additional studies published thereafter. Compared to previous systematic reviews our review has several strengths.…”

“…MCTs are a source of ketone bodies and are hydrolyzed to produce medium chain fatty acids (MCFAs) by the enzyme lipase [ 17 ]. MCFAs are absorbed and metabolized faster than long-chain fatty acids [ 18 ], as it is not dependent on the transporter protein for mitochondrial entry [ 19 ]. MCTs can be obtained from diet or exogenous supplementation [ 20 ].…”

“…Avgerinos et al [ 26 ], with literature search up to March, 2019, concluded that MCTs may improve cognition in patients with MCI and AD. Conversely, Castro et al [ 18 ] with literature search up to January 2021, reported otherwise. The discrepancy in findings could be due to the inclusion of different studies.…”

Is there evidence of a ketogenic effect of coconut oil? Commentary: Effect of the Mediterranean diet supplemented with nicotinamide riboside and pterostilbene and/or coconut oil on anthropometric variables in amyotrophic lateral sclerosis. A pilot study

“…Even when we followed the reference chains in a review on the topic ( 35 )—including the statement “Increased ketone levels, obtained through a balanced healthy diet containing ketone precursors such as coconut oil and MCT”—we did not identify empirical evidence targeting coconut oil or C12. Furthermore, a more recent related review ( 36 ) states that “dietary medium-chain triglycerides (MCTs) are metabolized into MCFAs (6 to 12 carbons in length) that are then preferentially metabolized into ketone bodies,” while their reference ( 37 ) targets a C8-supplement.…”