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Showing posts with label blood sugar. Show all posts
Showing posts with label blood sugar. Show all posts

Tuesday 1 January 2019

Apple Cider Vinegar (ACV), Phloretin, Phloridzin, Chlorogenic Acid, OAT3, Autism and Colon Cancer



Today’s post is only marginally related to autism, but does again show how some common food products have potential medical benefits.




Where I currently live people have been using apple cider vinegar (ACV) as a home remedy for generations. It is the apple part, rather than the vinegar part that is most interesting. I think they should continue with this home remedy, just be careful not to dissolve the enamel on their teeth. 
Rather surprisingly we can link ACV to improving Bumetanide effectiveness in autism and the chemoprotective effect of statins.
I have read so much research about statins, I do take Atorvastatin myself. The only downside is that research shows it does increase fasting glucose levels by about 0.4 mmol/L, exactly why nobody is quite sure.
If you want to further boost the chemoprotective power of statins it seems you may need a little help from something called Phloretin. Phloretin is a phenol that occurs in apples and the leaves of apple trees.  Apple cider vinegar (ACV) is rich in Phloretin.




Viability of HCT 116 colon cancer cells 48 hours after treatment with:-

PT = Phloretin
ATST = Atorvastatin
PT+ATST =  Phloretin + Atorvastatin

The closer to zero the better the result.  

If you want to improve insulin sensitivity and reduce fasting glucose levels it looks like it is the Phloridzin, a close relative of Phloretin, in apple cider vinegar that is useful.
If you want to improve the pharmacokinetics (how a drug is absorbed, distributed, metabolized, and excreted) of bumetanide you may also be able to use apple cider vinegar (ACV).  ACV also contains Chlorogenic acid which we we saw in an earlier post inhibits excretion of bumetanide through OAT3 (Organic acid transporter 3). Chlorogenic acid is also found in coffee.
In theory ACV will cause the level of bumetanide in blood to be higher, which might increase the amount that crosses the blood brain barrier and so make bumetanide a more potent autism drug. 
One odd proposed benefit of ACV is on GERD/reflux. You might have thought taking an acid would be the last thing that would help.
You would have thought that strong alcohol (also low pH, so very acidic) would also upset people with GERD/esophagitis, but some people I know swear that it is very beneficial.
In the case of GERD/esophagitis rather bizarrely I think it is the acetic acid (low pH) that is the reason why ACV seems to help some people.  I think it may help via feedback loops to trick the body into reducing its own acid production.

The drawbacks of Apple Cider Vinegar (ACV)
The acetic acid in apple cider vinegar can damage your teeth and your esophagus.  People avoid these problems by diluting ACV in a glass of water and rinsing their mouth with clean water afterwards.

ACV can lower potassium levels and it will lower blood glucose levels, which is good thing for most people, but diabetics would need to take care. Low potassium seems to worsen behaviour and increase sound sensitivity.
The Phloridzin in ACV is likely to reduce appetite, which for most people is a good thing, but for those few who struggle to gain weight it might be an issue.
ACV should lower triglycerides significantly, which might be bad for somebody. 



The results of the present study demonstrated that the antitumor efficacy of ATST could be enhanced at a relatively low dosage through the synergistic action with PT, which suggested the potential interaction of statins with other compounds in the food matrix. This interaction affects the efficacy of statins, and may explain the controversial results obtained in prior studies regarding the associations between statin use and the risk of colon cancer-associated mortality (27,28). As the dietary composition is different for each individual, this can result in varying statin efficacy. Conversely, different statins have different antitumor effects. In six colorectal cancer cell lines, including DLD1, HT29, SW620, HCT116, LoVo and colo320, simvastatin and fluvastatin showed strong growth suppressive effects. Atorvastatin demonstrated a relatively weak growth suppressive effect, whereas no growth suppressive effect was observed with pravastatin (29). This may be another reason for the paradoxical results regarding the antitumor effects of statins.
Therefore, the p21 gene may be the potential regulatory target underlying the G2/M phase arrest following the synergistic action of ATST and PT; more in depth future investigations are warranted.
In summary, the present study demonstrated that PT and ATST produce a powerful synergistic interaction in suppressing colon cancer cell growth. This process was accomplished via the synergistic induction of apoptosis and the arrest of the cell cycle at the G2/M checkpoint, which resulted from downregulated cdc2 activation following combined treatment.



Vinegars contain several bioactive compounds that are characterized according to the type of the raw material, such as grape vinegars and apple vinegars. Liquid chromatography coupled to diode array detection and electrospray ionization tandem mass spectrometry was used for identification and quantification of phenolic compounds. Antioxidant properties of vinegars were determined by 2,2diphenyl1picrylhydrazyl and 2,2′azinobis3ethylbenzthiazoline6sulphonic acid assays. Antimicrobial activities of vinegars were examined with an agar disc diffusion method with Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Gallic acid and chlorogenic acid were found to be the major phenolic acids accounting for the largest proportion of the total phenolic acid contents in grape vinegars and apple vinegars. Within the flavonols, quercetin3Ogalactoside and quercetin were detected as the major compounds in grape vinegars. Apple vinegars were characterized by phloridzin, phloretin and high chlorogenic acid content. Antimicrobial activity results indicated that grape vinegars exhibited higher antimicrobial activity against tested bacterial strains correlated with their higher antioxidant capacity.

In conclusion, gallic acid, tyrosol, protocatechuic acid, caftaric acid, catechin, epicatechin and syringic acid constituted the highest proportion of the total phenolic contents in GV. Chlorogenic acid, phloridzin and phloretin were found to be the major phenolic compounds in AV. With respect to antimicrobial and antioxidant activity results, GV showed higher antimicrobial and antioxidant activity than AV. With regard to phenolic composition of vinegars with their antioxidant capacities, two separate groups were obtained and characterized the vinegars with PCA based on the type of raw material. The results we obtained in this study extend our knowledge about the composition of vinegars obtained from different raw materials consumed in Turkey and allow the consumer to compare vinegar brands with the highest contents of beneficial compounds.


Coffee = chlorogenic acids  = 1,3- and 1,5-dicaffeoylquinic acid
Five compounds, 1,3- and 1,5-dicaffeoylquinic acid, ginkgolic acids (15 : 1) and (17 : 1), and epicatechin, significantly inhibited hOAT3 transport under similar conditions

3.2. Inhibition of hOAT3 by Natural Anionic Compounds and Flavonoids

Human OAT3 expressing cells showed about 4-fold greater accumulation of ES as compared to background control cells ( versus  pmol mg 10  , resp.). Similar to hOAT1, hOAT3-mediated ES uptake was completely (>96% inhibition) blocked by probenecid (Figure 4). Five of the compounds, 1,3- and 1,5-dicaffeoylquinic acid, epicatechin, and ginkgolic acids (15 : 1) and (17 : 1), significantly inhibited hOAT3-mediated transport at 50-fold excess (Figure 4). 1,3-Dicaffeoylquinic acid and ginkgolic acid (17 : 1) exhibited 41% inhibition, while 30–35% reduction of hOAT3-mediated ES uptake was observed for 1,5-dicaffeoylquinic acid, epicatechin, and ginkgolic acid (15 : 1). Catechin, 18β-glycyrrhetinic acid, and ursolic acid failed to produce significant inhibition. Based on the level of inhibition observed, values for all of these compounds would be greater than 50 μM, much higher than clinically relevant concentrations (Table 1). Therefore, further dose-response studies were not performed.


Phloridzin reduces blood glucose levels and improves lipids metabolism in streptozotocin-induced diabetic rats.

Abstract


Phloridzin is the specific and competitive inhibition of sodium/glucose cotransporters in the intestine (SGLT1) and kidney (SGLT2). This property which could be useful in the management of postprandial hyperglycemia in diabetes and related disorders. Phloridzin is one of the dihydrochalcones typically contained in apples and in apple-derived products. The effect of phloridzin orally doses 5, 10, 20 and 40 mg/kg body weight on diabetes was tested in a streptozotocin-induced rat model of diabetes type 1. From beneficial effect of this compound is significant reduction of blood glucose levels and improve dyslipidemia in diabetic rats. As a well-known consequence of becoming diabetic, urine volume and water intake were significantly increased. Administration of phloridzin reduced urine volume and water intake in a dose-dependent manner. Phloretin decreases of food consumption, as well as a marked lowering in the weight. In conclusion, this compound could be proposed as an antihyperglycemic and antihyperlipidemic agent in diabetes and potential therapeutic in obesity.  

Harvard Medical School vs the BBC?
You might expect when it comes to investigating health claims about apple cider vinegar (ACV) that Harvard would give you the science and the BBC would be just superficial.
While neither actually bother to use google to find what the active constituents of ACV might be, the BBC do actually make a trial in humans and measure the results in a lab.                                                                                             


It looks like if you have high triglycerides, or indeed high blood glucose, ACV is a potentially interesting non-drug therapy.
The guys at Harvard should watch the BBC and try a little harder next time.


Conclusion
Apple cider vinegar (ACV) is one home remedy that now has some science to support it. It is cheap and easy to access.
It is perhaps not relevant to many people with autism, but does show how medicine turns a blind eye to some old treatments that were stumbled upon as being effective hundreds of years ago.
When it comes to chemoprevention, the majority of cancers in males (prostate, colon, esophagus, bladder etc) have been shown in the research to be inhibited by statins. Some people know they have a familial risk of one or more of these cancers, would it not make sense that they be informed about chemoprevention?  It is much better to avoid cancer than to have to try to treat it.  In colon cancer it appears that phloretin from ACV might even be helpful.
We also saw that people with type 2 diabetes often find the beta cells in their pancreas die and so they stop making insulin, and yet a cheap calcium channel blocker can protect those insulin-producing cells and put off the day that insulin injections are required.
I did actually borrow my “polypill” name for my son’s autism therapy from another polypill that was designed to extend the healthy life expectancy of older people. Their pill has not been a huge success.

What is needed is a personalized polypill, whether it is for people with autism or typical adults from the age of 50.
I imagine, in 50 years time, when your family doctor has your genome on file, you probably will have a personalized little pill to help you minimize the risk of developing preventable disease.