04 Oct Can Alzheimers Be Reduced With Seaweed?
Dietary Sargassum fusiforme improves memory and reduces amyloid plaque load in an Alzheimer’s Disease Mouse Model was presented by Dr Monique Mulder at the Seagriculture 2019 Workshop in Ostende Belgium in September 2019.
Alzheimer’s Disease Background
Alzheimer’s disease (AD), also referred to simply as Alzheimer’s, is a chronic neurodegenerative disease that usually starts slowly and gradually worsens over time. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events.
An ever-increasing reduction in memory occurs in patients. Language proficiency, the ability to solve problems and other cognitive functions also decrease. The disease is not yet treatable. 44 million people worldwide suffer from Alzheimer’s disease. The costs involved are $ 1,000 billion. Due to the aging population, these numbers will increase drastically in the coming years. Over the past 20 years AD research has focused on either:
- Early detection. Catch early and stop progression.
- Drugs to stop the disease and the symptoms.
AD disease progression is complex.
- Brain shrinkage. As neurons are injured and die throughout the brain, connections between networks of neurons may break down, and many brain regions begin to shrink. By the final stages of Alzheimer’s, this process—called brain atrophy—is widespread, causing significant loss of brain volume.
- Beta amyloid. There is an abnormal build up of a protein called beta amyloid, which forms “plaques” outside the brain cells.
- Tangles. Inside the brain cells, another protein called tau builds up into “tangles”
Promising Improvement in Mouse Memory
Dr Mulder has been working for the past 15 years on dietary and genetic approaches to Alzheimer disease in animal models. Dr Mulder explains that “I ended up in the seaweed by accident. I have always been interested in the relationship between nutrition and health. We were looking for a certain substance (the plant sterol Saringosterol) and found in the scientific literature that this substance had been detected in seaweed. Then it appeared that mice that we had fed with seaweed performed better in the field of cognition (information processing in the brain). That was the trigger for further research.”.
Seaweed Reduced Brain Atrophy
The brain atrophy is due to lack of cholesterol. The brain cannot get cholesterol from the body as cholesterol cannot move across the Blood Brain barrier. Dr Mulder’s previous work showed that the memory of mice with Alzheimer’s disease improves if the transport of cholesterol in the brain is activated with synthetic substances that stimulate certain receptors (LXR α and β). Unfortunately, serious side effects occur, such as fatty liver and accumulation of fatty substances in the blood, so that ruled out the synthetics.
But with in Sargassum, a natural substance was (Saringosterol) did work. It activated fat transport in the brain via LXR β. In mice with Alzheimer’s disease, she saw an improvement in memory and fewer brain abnormalities when they let them eat seaweed. Moreover, no adverse side effects occurred.
Dr Mulder presented that the key issue is that the brain has to synthesis its own cholesterol – there is no blood to brain transfer. Defective synthesis in the brain causes brain disease. The regulation is with compounds called LXR. Brain sterols also play a part.
Details of the Research
In previous published work, when they increased the cholesterol turnover by LXR activation with compounds at about 0.015% w/w then mice improved their object recognition and object location tasks. (Did not affect mice without AD).
It turns out that common plant sterols (such as those from Sargassum) can enter the brain, and they are very similar to cholesterol but the ones they have tried previously do not change the LXR levels.
It is not simple, as the compounds have to turn on / turn off genes. These compounds have to “agonist”. An agonist is a chemical that binds to a receptor and activates the receptor to produce a biological response.
A few years the research discovered that a sterol from Sargassum fusiforme is a novel selective LXR. The work at Erasmuwas done in collaboration with Shulalongkorn University in Bangkok.
The researchers compared a range of plants and compounds including Azadirachta indica (neem oil) which has reputed health benefits. You can see the much larger response from Sargassum
This figure shows that the Sargassum stopped the folding of the brain which is associated with brain atrophy and tangles. There was no sign of fatty liver from the eating of the sterols, and that is consistent with research with research with the seaweed Kappaphycus alvarezii where it was protective.
This figure shows that Sargassum actually affected 3 of the genes that regulate the LXR target genes.
The microbiome: A target for Alzheimer disease?
All the evidence from this work, and from others such as Lin 2019 shows that the getting the gut from a leaky gut to a healthy gut is subtle but very important. The Toll Like Receptors (TLRs) play a huge part in the regulation. The Blood Brain Barrier (BBB) is very important as well. Normally nothing gets into the brain except glucose.
From Lin Fig. 1. Potential implications of TLRs and gut-brain-axis for AD. In healthy subjects, the gut epithelium is guaranteed by tight junctions between the cells. TLRs are expressed on macrophages, dendritic cells (DCs), and intestinal epithelial cells, serving as sentinels to monitor the pathogens in gut. Vagus nerve appears to modulate communication between the gut and the brain. The whole microenvironment maintains in homeostasis. During aging, the tight junction of intestinal and BBB become permeable. In AD patients, the diversity of gut microbiota decreased, while the population of pro-inflammation bacteria increased. Bacteria and their excretions could cross the leaky gut and then activate the TLRs in epithelium, IECs and macrophages, leading to production of pro-inflammation cytokines. These cytokines make their way through circulation or vague nerves to the brain, enlarge the neuro-inflammatory responses, and promote neuro-degeneration in CNS.
Findings from the Current Research
Seaweed improved memory in mice. There are multiple reasons.
- Sargassum seaweed is much more effective than other compounds or “anti-oxidants”
- Sargassum increased cholesterol levels and that shows promise that brains won’t shrink.
- Sargassum activates LXR-targets genes in the brain and there is half as much brain folding (i.e. degradation) and there has been reduction in beta amyloid and less tangles.
- There is no downside. Sargassum did not induce fatty liver or other side effects.
Will this Work in Humans?
In over 400 animal studies since 2002, the failure of drug development has been over 99% when the drugs trials were transitioned from animal studies to human studies. These studies by Mulder and her teams are different in that the Sargassum appears to be affecting all 3 of the causes of dementia.
- Plant sterols cross the blood-brain barrier to give a supply of cholesterol like plant sterols that are used in brain regeneration.
- One of the compounds works on the LXRb gene expression process
- There is less amyloid plaque deposited
So this is very promising work. Would you consume seaweed now to prevent AD?
Are some animal models more equal than others? A case study on the translational value of animal models of efficacy for Alzheimer’s disease. Veening-Griffioen et al Eur J Pharmacol. 2019 Sep 15;859:172524. doi: 10.1016/j.ejphar.2019.172524.
Lin C, Zhao, S et al 2019 Microbiota-gut-brain axis and toll-like receptors in Alzheimer’s disease 2019 Computational and Structural Biotechnology Journal Volume 17, 2019, Pages 1309-1317
24(S)-Saringosterol from edible marine seaweed Sargassum fusiforme is a novel selective LXRβ agonist. Chen et al J Agric Food Chem. 2014 Jul 2;62(26):6130-7. doi: 10.1021/jf500083r.
Good Catch! https://amazingerasmusmc.nl/actueel/goeie-vangst/