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The Cholesterol-Brain Connection
Can a cholesterol-cousin in plant foods help deflect mental decline?

01/08/2018 By Kimberley Day with Craig Weatherby

As the old saying goes, aging ain’t for the faint of heart.

Mental decline is especially fearful, because fuzzy thinking and memory corrodes life capacities, self-image, and confidence.

Thankfully, exercise and diet can dramatically slow these age-related declines, including loss of mental capacity.

Now, new evidence suggests that plant-source counterparts to cholesterol — called sterols — may help delay, deflect, or alleviate Alzheimer’s disease and other forms of dementia.

The cholesterol-Alzheimer’s connection
Cholesterol is essential to many aspects of human health.

Without it, you couldn’t create cell membranes, hormones, vitamin D, or the bile acids that help digest fat.

Cholesterol is also critical to critical cognitive (thinking-memory) capacities, and brain health is clearly affected by your blood fat and cholesterol profiles.

High blood cholesterol levels — especially high levels of cholesterol that’s been oxidized by free radicals (so-called oxysterols) — can raise the risk for Alzheimer’s disease and other forms of dementia.

These risk factors are linked to sedentary lifestyles and to junky Western diets, both of which promote dementia risk factors like chronic, excessive inflammation and oxidation.

The key problems with high brain cholesterol
The term “lipid” covers fats, oils, waxes, triglycerides, and sterols — including cholesterol.

And your brain is especially susceptible to oxidation because of its extremely high fat (lipid) content.

Your brain is about 60 percent fat, with the most abundant and critical one being omega-3 DHA, which is found only in seafood and algae.

(People can survive on the tiny amounts of DHA we make from the omega-3 fat found in a dark, leafy greens and certain nuts and seeds — but there’s ample evidence that the pre-formed DHA in seafood or supplements benefits heart and brain health.)

Cholesterol constitutes about one-quarter of the lipids in your brain, where it occurs in the various forms (LDL, VLDL, and HDL) linked to cardiovascular health or illness.

Because your brain uses about 25 percent of the oxygen you breathe, its cholesterol is at high risk of being oxidized — a risk greatly heightened by sugary, starchy diets, a lack of antioxidants from colorful plant foods, and sedentary lifestyles.

High cholesterol levels in the brain also promote the production of the amyloid-beta proteins that form the plaques associated with Alzheimer’s.

The combination of excess cholesterol, abundant oxygen, and unhealthful lifestyles creates a perfect storm of dementia risk.

Let's look at the anti-Alzheimer’s hopes for statin drugs, and then examine encouraging new evidence concerning the plant-source cholesterol counterparts called sterols.

Do statin drugs help deflect dementia?
Statin drugs inhibit inflammation and oxidation while lowering cholesterol levels.

And that's fueled hopes that statins might help prevent, delay, or alleviate Alzheimer’s.

However, statins lower cholesterol by blocking the enzyme (HMG CoA reductase) needed to produce cholesterol — which, as we’ve seen, is critical to many essential functions including brain performance.

In fact, this enzyme-blocking activity of statins explains why the U.S. Food and Drug Administration (FDA) cautions that these drugs may impair thinking and memory.

Animal studies and a couple of preliminary human studies indicated that statins — which are primarily used to treat high cholesterol — might serve as allies against Alzheimer’s.

But when researchers from Harvard Medical School, Johns Hopkins University, and Chicago’s Rush Institute for Healthy Aging reviewed the relevant evidence, they found no proof that statins prevent mental decline or dementia (Power MC et al. 2015).

And Irish researchers who conducted an evidence review — under the rigorous standards set by the Cochrane Collaboration — came to an even clearer negative conclusion: “There is good evidence that statins … do not prevent cognitive decline or dementia.” (McGuinness B et al. 2016)

Fortunately, a close cousin to cholesterol — found in plant foods — may offer a far safer way to reduce cholesterol while supporting memory and possibly protecting against Alzheimer’s.

Beta-sitosterol and brain health
Many plant foods contain waxy “phyto-sterols” such as stanols and sitosterols.

Phyto-sterols can help to safely lower high blood cholesterol levels — which is why the American Heart Association recommends them for that purpose.

Beta-sitosterol is the phyto-sterol that most closely resembles cholesterol, and it has shown evidence of anti-Alzheimer’s effects, probably related in part to its cholesterol-lowering effects.

Recently, Pakistani researchers conducted lab studies on the effects of beta-sitosterol extracted from a traditional herbal remedy for dementia (marshpepper knotweed).

The encouraging results of their investigation add to the evidence suggesting that beta-sitosterol may help protect brain health (Ayaz M, et al. 2017)

Before reviewing their findings, we need to quickly review the role that acetylcholine — an important brain neurotransmitter — and the cholinesterase enzymes that break it down play in Alzheimer’s:

  • People with Alzheimer's disease have low brain levels of acetylcholine.
  • If cholinesterase enzymes are blocked, more acetylcholine is available for communication between brain cells.
  • Anti-Alzheimer’s drugs like Aricept, Exelon, and Razadyne work by blocking cholinesterase enzymes.

The Pakistani team tested beta-sitosterol in test tube (in vitro) and rodent (in vivo) studies to determine its antioxidant activity, and its ability to block cholinesterase enzymes.

The results showed that beta-sitosterol blocked cholinesterase enzymes and produced gradual improvement in working memory and motor coordination in swimming and maze-running tests.

Beta-sitosterol also exerted substantial antioxidant effects, and thereby reduced the amounts of free oxygen radicals in brain tissues — which drive the chronic, excessive inflammation and oxidation known to promote dementia.

In light of their findings, the Pakistani researchers proposed a reasonable possibility: “Beta-sitosterol is a potential compound for the management of memory deficit disorders like AD [Alzheimer’s disease].”

Critically, there’s now good evidence that beta-sitosterol — and other phyto-sterols — cross the blood-brain barrier, making them credible dietary allies against dementia.

And, beta-sitosterol appears to enhance the productivity of the cellular energy factories called mitochondria — which don't work well in people with dementia (Shi C et al. 2012).

Interestingly, evidence published by a German-Finnish research team suggests that another phyto-sterol — called stigmasterol — may be an equally effective ally against Alzheimer’s and other forms of dementia (Burg VK et al. 2013).

Where can you find beta-sitosterol?
Foods rich in beta-sitosterol and stigmasterol include nuts, seeds, legumes (beans and lentils), and many fruits and vegetables.

You can also take beta-sitosterol in supplement form, with experts recommending 1,500-2,000 mg daily, before meals.


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