Garlic in Autism – Miscreant Microglia? ACE inhibition? or even Nitric Oxide?

Many people avoid garlic because it gives you bad breath, but if you eat enough of it, it can be a potent drug.

There is a substantial amount of research about garlic and general health - it is consistently positive. However, there is an odd resistance to tell people about it.  A good example is this quote from the website of the UK’s National Health Service.

“Studies using high concentrations of garlic extracts have been associated with improved blood circulation, healthier cholesterol levels and lower blood pressure, all of which reduce the risk of cardiovascular disease. However, current evidence does not support the use of garlic supplements to improve health.”

Which sounds like “garlic is really good for you, but don’t eat it”.

Garlic has numerous different modes of action that have a potential health benefit, the best known relate to your heart and circulation, but there are others. 

Garlic and Neurological Conditions with Activated Microglia

There is recent research showing positive effects on the activated microglia.  Activated microglia, the brain’s immune cells, is a feature of autism and other diseases, like Alzheimer’s.

Some people try and treat activated microglia in autism using therapies like:-

·        Minocycline

·        Ibudilast

Some researchers use garlic to try to minimize the damage caused by activated microglia.

They tend to use capsules that contain aged garlic.  It is important not to cook it and there is a difference between fresh garlic, aged garlic and steamed garlic. 

Table 1. Principal Organosulfur Compounds in Commercial Garlic Preparations
Product	Principal Organosulfur Compounds	Delivers allicin-derived compounds?
Fresh garlic cloves	Cysteine sulfoxides (Alliin) γ-glutamylcysteines	Yes, when chopped, crushed, or chewed raw. Minimal, when garlic cloves are cooked before crushing or chopping.
Powdered garlic (tablets)	Cysteine sulfoxides (Alliin) γ-glutamylcysteines	Varies greatly among commercial products. Enteric-coated tablets that pass the USP allicin release test are likely to provide the most.
Steam distilled garlic oil (capsules)	Diallyl disulfide Diallyl trisulfide Allyl methyl trisulfide	Yes
Garlic oil macerate (capsules)	Vinyldithiins Ajoene Diallyl trisulfide	Yes
Aged garlic extract™ (tablets or capsules)	S-Allylcysteine S-Allylmercaptocysteine S-1-Propenylcysteine	Minimal

  

Source: -http://lpi.oregonstate.edu/mic/food-beverages/garlic

  

Benefits Of Garlic Extract May Protect Brain From Inflammation, Diseases Like Alzheimer's

Now, a new study finds that one of these compounds, called FruArg, may protect the brain from age-related disease like dementia and Alzheimer’s.

As a carbohydrate derivative of garlic, there’s a relatively high concentration of FruArg in aged garlic extract (AGE), the authors wrote — AGE is typically sold as supplements. Looking at isolated FruArg’s impact on brain cells, researchers from the University of Missouri found it could protect brain cells from an overexcited immune response caused by environmental factors like pollution and smoking, as well as normal aging, brain injuries, and drinking lots of alcohol.

“Microglia are immune cells in the brain and spinal cord that are the first and main line of defense in the central nervous system,” said lead author Zezong Gu, an associate professor of pathology and anatomical sciences at the university’s School of Medicine. “Unlike other mature brain cells that seldom regenerate themselves, microglial cells respond to inflammation and environmental stresses by multiplying. By massing themselves and migrating toward an injury site, they are able to respond to inflammation and protect other brain cells from destruction.”

But microglia also tread a line between benefiting the body and harming it, protecting only to an extent. A byproduct of their function is nitric oxide, a free radical. And when a lot of microglia are produced, so are nitric oxide molecules, which can lead to oxidative stress and inflammation within the brain and nervous system. As we’ve all heard before, however, antioxidants fight oxidative stress, and in this case, that antioxidant compound is FruArg. 

For their study, Gu and his colleagues applied stress to a cell model of microglial cells and then added FruArg to them once nitric oxide concentrations rose. They found the microglial cells “adapted to the stress by reducing the amount of nitric oxide they produced.” What’s more, FruArg also promoted the production of antioxidants, which then went on to protect and heal other brain cells. “This helps us understand how garlic benefits the brain by making it more resilient to the stress and inflammation associated with neurological diseases and aging,” Gu said. 

Full study:- 

Proteomic analysis of the effects of aged garlic extract and its FruArg component on lipopolysaccharide-induced neuroinflammatory response in microglial cells.

Collectively, these results suggest that AGE and FruArg attenuate neuroinflammatory responses and promote resilience in LPS-activated BV-2 cells by suppressing NO production and by regulating expression of multiple protein targets associated with oxidative stress. 

Effects of aged garlic (AGE) extract and FruArg on gene expression and signaling pathways in lipopolysaccharide-activated microglial cells 

These effects could be modulated by treatment with both AGE and FruArg. These findings suggests that AGE and FruArg are capable of alleviating oxidative stress and neuroinflammatory responses stimulated by LPS in BV-2 cells.

  

Evaluating the Anti-Neuroinflammatory Capacity of Raw and Steamed Garlic as Well as Five Organosulfur Compounds

Abstract

: The anti-neuroinflammatory capacities of raw and steamed garlic extracts as well as five organosulfur compounds (OSCs) were examined in lipopolysaccharide (LPS)-stimulated BV2 microglia. According to those results, steaming pretreatment blocked the formation of alliinase-catalyzed OSCs such as allicin and diallyl trisulfide (DATS) in crushed garlic. Raw garlic, but not steamed garlic, dose-dependently attenuated the production of LPS-induced nitric oxide (NO), interleukin-1β (IL-1β), tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein-1 (MCP-1). DATS and diallyl disulfide at 200 and 400 μM, respectively, displayed significant anti-neuroinflammatory activity. Meanwhile, even at 1 mM, diallyl sulfide, S-allyl cysteine and alliin did not display such activity. Inhibition of nuclear factor-κB activation was the mechanism underlying this protective effect of raw garlic and DATS. Analysis results indicated that the anti-neuroinflammatory capacity of raw garlic is due to the alliin-derived OSCs. Importantly, DATS is a highly promising therapeutic candidate for treating inflammation-related neurodegenerative diseases.

As expected, raw garlic extract inhibited NO, proinflammatory cytokine, and chemokine production by through suppression of NF-κB activation in LPS-activated BV2 microglia; it also had a potent anti-neuroinflammatory capacity. Additionally, steaming pretreatment abolished both the anti-neuroinflammatory capacity and alliin-derived OSCs formation of garlic simultaneously. In sum, this study demonstrates that alliinase catalysis and chemical transformation are essential for the formation of active OSCs, which are responsible for the anti-neuroinflammatory capacity of garlic. Based on above, it is suggested that consumers to crush or cut raw garlic before cooking in order to obtain more health benefits of garlic. As one of the most potent anti-neuroinflammatory components of garlic, DATS is highly promising for use as a dietary agent to prevent inflammation-related neurodegenerative disease. 

Garlic as an ACE inhibitor 

We saw in a recent post how too much angiotensin II is likely a problem in schizophrenia and some autism.  The biomarker of those affected would be high levels of IL-17a. 

Targeting Angiotensin in Schizophrenia and Some Autism

There are numerous references in the literature to garlic being an ACE inhibitor, which will reduce the level of angiotensin II and hence IL-17 and IL-17a. 

Garlic extract reduces serum angiotensin converting enzyme (ACE) activity in nondiabetic and streptozotocin-diabetic rats. 

Although garlic extract administration had no significant effect on serum glucose, it significantly strongly decreased the serum ACE activity. ACE activity was higher in diabetic than nondiabetic rats, but in diabetic animals treated with garlic extract, the elevation of ACE activity did not occur. These results suggest that garlic extract might have value as ACE inhibitor to prevent some vascular complications of diabetes mellitus.

So perhaps some people with autism, who respond to garlic are actually not feeling the microglia effect, but actually the angiotensin II reducing effect. 

Potent activation of nitric oxide synthase by garlic: a basis for its therapeutic applications. 

Activation of calcium-dependent nitric oxide synthase and the subsequent production of nitric oxide is probably the most novel mechanism yet claimed by which garlic can exert its therapeutic properties.

   

Conclusion  

Garlic has numerous health benefits and different types of processing lead to very different chemical compositions.  So it does depend how you take your garlic.

Does any type of garlic provide a benefit in any type of autism? 

For one reader fresh garlic is effective in treating autism, whereas aged garlic is not; this is not what she expected. This would of course suggest something about its mode of action. 

Perhaps some people are actually benefiting from a reduction in angiotensin II.  Or maybe it is production of nitric oxide?

There are actually other natural ACE inhibitors that you might be using by accident.

People trying to make tasty drinkable sulforaphane, using the Australian mixture of broccoli and pomegranate powders, are actually also making an ACE inhibitor.  

Effect of pomegranate juice on Angiotensin II-induced hypertension in diabetic wistarrats

The results suggest that the PJ extract could prevent the development of high blood pressure induced by Ang II in diabetic rats probably by combating the oxidative stress induced by diabetes and Ang II and by inhibiting ACE activity.

Pharmacological review on Natural ACE inhibitors 

All we can say is some people with autism respond to specific types of garlic, but nobody can be sure what the mode of action is; there are several possible credible explanations.