I’ve taken canagliflozin and empagliflozin for most of the past year with no UTI issues. I think it may only be an increased risk for women, not men.
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No UTI despite taking it for a year now. About 6 months at 10mg and now 6 months at 25mg.
I drink a lot of water and my only source of sugar is fruit. My last labs I did have borderline glucosuria–which makes sense given that I’m peeing out the sugars that I do take in. But my urine glucose was just a hair over normal. I can imagine if you’re eating lots of carbs, that would be significantly higher, which in turn would increase your risk of UTI.
I also take acarbose any time I eat fruit (though I’m never quite sure how effective it is against fruit–I think it helps vs sucrose but not fructose, and fruits are a combo) as well as mullberry extract.
Despite being “keto plus fruit” I was pushing into prediabetes pretty hard before I started this, and it has dramatically reduced my fasting blood glucose (from around 5.8 to 4.7) and my HBA1C (to a less dramatic extent).
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I have been using luteolin (a fructokinase inhibitor) before when I take fructose. You may want to look at this. However I have no idea about the optimal dosage or desired timing before consumption of fruit.
I just do 100-200 mg and hope it provides some benefits.
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Rick Johnson and David Perlmutter’s views on Fructose and Uric acid make me wary of fruits. When I consume fruits, it’s usually lower GI (like berries) and also comes with a lot of polyphenols (like berries).
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That’s a great suggestion, thank you! I’ve been wondering whether there are any accessible fructokinase inhibitors. Rick Johnson’s episodes on Peter Attia are among my favourites, and I just bought his book.
I’ve been torn on fruit. On the one hand, the evidence against fructose is compelling. On the other, fruit consumption consistently seems to be correlated with longevity.
E.g., In this study, the only statistically significant variables were fruit (+, p=0.001) and processed meat (-, p=.01). Even veggies were p= 0.05/0.06:
" DNA methylation-based biomarkers of aging were slowed down in a two-year diet and physical activity intervention trial: the DAMA study."
https://doi.org/10.1111/acel.13439
Any suggested source for the luteolin?
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Mike Lustgarten has published a lot about Luteolin - I recommend you review it:
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I use pipingrock.com just because they ship cheaply to where I live.
Based on the Rick Johnson’s episode, I also try to ensure I’m drinking enough water when I eat fruits or salt. Psyllium husk is not a fructokinase inhibitor but perhaps it reduces the speed of uptake of fructose as well.
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Yeah but I thought he said in the interview that fruits also have alot of vitamins and minerals that help protect against fructose issues that would arise in comparison to dried fruits or fruit concentrate juice. In fact he says he doesnt tell people to not eat fruits, he just says not to overdue it
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Interestingly, back in the day, fructose was considered the “good” sugar as opposed to cane and beet sugars.
"This was promoted by: Adelle Davis (25 February 1904 – 31 May 1974) was an American author and nutritionist, considered “the most famous nutritionist in the early to mid-20th century.”[1]: 150 She was an advocate for improved health through better nutrition. "
Adelle Davis - Wikipedia(25%20February%201904,improved%20health%20through%20better%20nutrition.
She was not promoting sugar as anything but bad, but if you use sugar, use fructose.
The thinking was because it came from “healthy” fruits it must be better.
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I believe a lot of one’s microbiome uses fructose as a fuel, so it’s worth having a little bit, just not a lot.
Fantastic new paper on Cana and it’s similar effects to 17AE, Rapa and ACA when it comes to MTOR activities and anti-aging.
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Interesting. Perhaps the thinking was insulin. No insulin effect from fructose. In sports performance the idea is fructose and glucose use separate uptake pathways so you can consume more per hour (during exercise) using both.
Yes - full paper and info already posted here: Canagliflozin shares common mTOR and MAPK signaling mechanisms with other lifespan extension treatments
My apologies, I don’t mean to duplicate efforts. I should have looked.
No problem. There are a ton of posts and most people don’t have time to read them all.
A new paper from Richard Miller’s lab on Canagliflozin:
Hypothalamic Sex-Specific Metabolic Shift by Canagliflozin during Aging
Hashan S.M Jayarathne, Ryan Sullivan, Luke Stilgenbauer, Lucas Kniess Debarba, Artur Kuchumov, Lisa Koshko, Sydney Scofield, Wanqing Liu, Brett C Ginsburg, Richard A Miller and Marianna Sadagurski
The hypothalamus undergoes significant changes with aging and plays crucial roles in age-related metabolic alterations. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are anti-diabetic agents that promote glucose excretion, and promote metabolic homeostasis. Recent studies have shown that SGLT2i, Canagliflozin (Cana), can extend the median survival of genetically heterogeneous UM-HET3 male mice and improve central metabolic control via increases in hypothalamic insulin responsiveness in aged males, as well as reduced age-associated hypothalamic inflammation. We studied the long- and short-term effects of Cana on hypothalamic metabolic control in UM-HET3 mice. We show that Cana treatment reduced body weight and fat mass in male mice that was associated with enhanced glucose tolerance and insulin sensitivity observed by 12 months. Indirect calorimetry showed that short-term Cana treatment (5 months) increased energy expenditure in male, but not female mice, at 12 months of age. Long-term Cana treatment (18 months) increased metabolic rates in both sexes, and markedly increasing formation of both orexigenic and anorexigenic projections to the paraventricular nucleus of the hypothalamus (PVH) mostly in females by 25 months. Hypothalamic RNA-sequencing analysis revealed sex-specific genes and signaling pathways related to insulin signaling, glycogen catabolic pathway, neuropeptide signaling, and mitochondrial function upregulated by Cana, with males showing a more pronounced and sustained effect on metabolic pathways at both age groups. Overall, our data provide critical evidence for sex-specific mechanisms that are impacted by Cana during aging suggesting key targets of hypothalamic Cana-induced neuroprotection for metabolic control.
bioRxiv. posted 23 March 2024, 10.1101/2024.03.21.586115
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Cana is actually both SGLT1i and 2i.
My understanding is that it hence actually does also act via lowering glucose effects at the intestine level. See eg below. Does that make sense?
SGLT1 is involved in glucose absorption by the intestinal absorptive epithelial cells, and it regulates glucose-dependent incretin secretion from enteroendocrine cells such as GLP-1-secreting L cells and GIP-secreting K cells [10].
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But is that sglt1 inhibition in the intestine by canagliflozin clinically significant enough to have a real world effect on glucose absorption?
For Cana my understanding is yes (though perhaps not so for Empa and Dapa and others).
@Davin8r Is your understanding different re Cana?
My bad, sorry, yes, you’re right – I’d always thought the sglt1 inhibition was clinically insignificant because it doesn’t cause flatulence/diarrhea in the way acarbose does, but that’s because cana just slows down (but doesn’t block) absorption in the small intestine.
Unfortunately, I can’t edit my original post from 3 years ago😬
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