New study from the CAPS2 (Carbohydrate and Prostate Study 2) team. led by Steve Freedland.
"Accumulating evidence suggest a role of gut microbiota in urologic health including prostate cancer (PC), potentially via its impact on intestinal permeability (IP). When the gut microbiota community is disrupted or imbalanced, i.e. gut dysbiosis, intestinal barrier function may be impaired and thus increase permeability. Greater IP allows increased leakage of intestinal lumen fluid, macromolecules, leukocytes, toxins and compounds into circulation that may contribute to inflammation [4]. IP, as a marker of gut microbiota health, may be involved in the development of PC and/or responses to treatments, and inflammation may be a potential mediating mechanism ..."
"Zonulin is a ... protein with regulating function on intestinal barriers and has been commonly used as a marker for IP ..."
"Our findings showed that weight loss improved IP in PC patients while consuming a LCD (low-carbohydrate diet) (N = 26). This is consistent with a previous study showing that weight loss improved IP in a non-cancer population. In addition, our data showed that weight loss directly benefits PSADT and improvement in IP, as shown by reduction in zonulin, may also benefit PSADT."
However, there was no reduction in hsCRP, which was the only inflammation marker tracked.
One of the benefits of a low-carb diet might be a reduction in visceral fat. Hormones secreted by visceral fat potentially have a profound effect on PCa progression. Weight loss is a poor surrogate for visceral fat loss, which can only be measured via a scan.
A low-carb diet is likely to affect many of the bacterial populations residing in the gut. It would be interesting to know what, other than Zonulin, was affected. There might be non-cancer studies that shed light on this.
Weight loss via a low-carbohydrate diet improved the intestinal permeability marker, zonulin, in prostate cancer patients
Pao-Hwa Lin 1 , Lauren Howard 2 , Stephen J Freedland 3 4 5
Affiliations expand
PMID: 35486445 DOI: 10.1080/07853890.2022.2069853
Abstract
Background: Accumulating evidence suggest that gut microbiota may impact urologic health including prostate cancer (PC), potentially via affecting intestinal permeability (IP). Studies have indicated that disrupted IP may be improved by healthy diets and weight loss. In the Carbohydrate and Prostate Study 2 (CAPS2) clinical trial, which showed that a low-carbohydrate diet (LCD) reduced weight significantly in men with PC and suggestively slowed PC disease progression, we explored the impact of LCD on an IP marker, zonulin and an inflammation marker, high sensitivity C-reactive protein (hsCRP).
Methods: CAPS2 was a 6-month randomized controlled trial testing a LCD intervention vs. control on PC progression using prostate-specific antigen doubling time (PSADT) as the marker. All 45 participants had prior primary PC treatment, PSADT >3 and <36 months, and body mass index (BMI) ≥24 kg/m2.
Results: At 6-month, zonulin decreased in the LCD arm (median -8.3%, IQR -16.6, 0.3%) while the control increased slightly (median 1.4%, IQR -3.0, 13.3%; p = .014). No changes were observed in hsCRP. Linear regression models showed that weight change was significantly associated with log(PSADT) such that the greater the weight loss, the longer the PSADT(p = .003). There was a similar inverse trend between change in zonulin and log(PSADT) (p = .050). Nevertheless, the mediation analysis showed that zonulin was not a significant intermediary mechanism of the effect of weight change on PSADT (p = .3).
Conclusion: Future studies are merited to examine further the potential association of IP with inflammation and to clarify if improvement in IP is associated with decreased PC progression. Trial registration: NCT01763944. KEY MESSAGESGut microbiota may impact urologic health including prostate cancer, potentially via affecting intestinal permeability.Weight loss significantly improved intestinal permeability in prostate cancer patients.Improvement in intestinal permeability was associated with slowed prostate cancer progression as indicated by the PSA doubling time.
Keywords: Diet; gut permeability; low-carbohydrate diet; prostate cancer.
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pjoshea13
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"The LCD arm was instructed by a dietitian to limit carbohydrate intake to ≤20 grams/day (25). Patients were provided a list of low-carbohydrate foods to choose from (e.g., greens, fats, lean meat, and seafood) and a list of moderate/high-carbohydrate foods to avoid (e.g., bread, pasta, grains, legumes, starchy vegetables). Grains and starchy vegetables are high in carbohydrates (e.g., 1 slice of bread contains about 12 g carbohydrate); thus, these food items were on the avoid list. Sample menus and recipes were also provided. No other limits were given." [1]
I eat tons of whole grains (groats), whole sweet potatoes, popcorn, beans, etc. I'm not sure how to analyze my gut bacteria, but I haven't seen a downside after three years on a whole food plant based diet. The debate continues.
Regarding visceral fat loss from LCD I am an example. In 2019 I was overweight (188#), sarcopenia obesity from ADT. Had two new pelvic LNs and required pelvic RT. Scans including PSMA PET and CT for planning RT showed substantial visceral fat, which made my RO happy in that it protected pelvic and abdominal organs at risk for radiation injury. He asked me not to lose any weight until the treatments were over.Right afterward I went on a very low carbohydrate diet (ketogenic) combined with one meal a day intermittent fasting. I rapidly and effortlessly loss the excess fat down to a lifetime adult leanest weight of 144#, where I remain since 2022. (Not to mention the sarcopenia revealed when the fat was gone. That required testosterone to correct.)
Last month a follow up PSMA PET scan revealed two additional very small LNs not previously visible. Scans including high-resolution CT and MRI for planning SBRT showed very very little visceral fat. As I continue on LCD with OMAD. I no longer need to be so strict with carb restrictions (no longer full keto) and happily remain at 144#. BTW my RO was very nervous about my SBRT (completed 2 weeks ago) because no margin of separation from adjacent organs at risk. Next week I am off to Perth AU for “Part II”, Lu-PSMA-J591 treatments to go after remaining unseen micro-mets. Paul
Thank you Patrick. I am coordinating with Marnie and Ron in Sydney. She sends regards to you this morning. I will be flying to Sydney for a week between treatments and looking forward to much interactions with them. G’day
Interestingly this paper (see reference at end of post) reports some evidence that plant photochemicals often used as complementary PCa treatments had a beneficial effect on leaky gut syndrome (LGS).
From Table 1 of the paper.
Berberine
Anthocyanis
Curcumin
Resveratrol
Baicalin
Rhein
Some other points with regards to diet, drugs, probiotics, and vitamins A and D are summarized in the conclusions below.
8. Conclusions and Future Perspective
Translocation of bacteria or endotoxin in LGS is associated with GI diseases. Elevated intestinal barrier permeability may be the first step in the development of various GI disorders, given that undigested food particles, bacterial toxins, and germs can pass through the “leaky” gut wall and into the bloodstream, triggering the immune system and causing persistent inflammation. Of note, clinicians have a large problem with recognition of LGS because there are several symptoms overlapping with other common GI diseases, such as diarrhea or constipation. Moreover, there is no gold standard procedure for a clear characterization of the barrier function. Currently available tests for barrier function measure very different endpoints, and therefore, their clinical significance and relevance are unclear [10].
Intestinal bacteria play an important role in the human body. Most of the bacteria have a positive effect on our health and contribute to many natural processes, including metabolism of indigestible compounds, synthesis of vitamins, protection against pathogen colonization, and contribution to the host immune system. On the other hand, the imbalanced gut bacterial composition leads to serious health problems. Various factors may influence BT in the GI tract, e.g., (1) diet, mainly fat and saccharide composition, (2) probiotics, (3) dietary supplements, such as amino acids and vitamins, and (4) medicines. Many reports indicate that high-fat and high-sugar diets disturb the composition of the bacterial microflora and induce a harmful effect on intestinal permeability. Importantly, probiotics mainly consist of Bifidobacteria and Lactobacillus to prevent colon endotoxemia. Furthermore, vitamins, especially vitamins D and A, also play an important role in the integrity of intestinal epithelium. Patients suffering from IBD have decreased levels of vitamin D3, and it is also associated with a higher risk of Clostridium difficile infection in IBD individuals. Additionally, lower vitamin D concentration correlates with an increase in zonulin and plasma endotoxin serum level, suggesting their further impact on intestinal permeability. Available treatments for patients with LGS are based on the underlying condition, which often includes leaky gut as a symptom (Figure 2). Accordingly, anti-inflammatory drugs and immune system suppressors are prescribed in patients with IBD, whereas anticholinergics and ligands of serotonin receptors are recommended for patients with IBS, etc. Odenwald et al. [172] noticed that no FDA-approved agents targeting epithelial barriers are presently available. However, promising approaches to target the LGS are being investigated. Interestingly, the effect of nutrients, probiotics, and even vitamins on barrier function and the alleviation of clinical symptoms of GI diseases though preventing BT is impressive, suggesting that these ingredients should be considered as promising candidates for the treatment of patients suffering from the LGS.
Preventing Bacterial Translocation in Patients with Leaky Gut Syndrome: Nutrition and Pharmacological Treatment Options
by Agata Twardowska, Adam MakaroORCID, Agata BiniendaORCID, Jakub FichnaORCID and Maciej Salaga *ORCID
Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, 90-419 Lodz, Poland
*
Author to whom correspondence should be addressed.
Academic Editors: Jérôme Roy and Nobuyuki Takahashi
I have practiced and studied exercise and diet for decades. Having low body fat and good muscle mass/strength (for your age) is very clearly associated with lower PCa and all-cause mortality,
In my personal experience (most studies concur but there are outliers), LCD is not the secret to fat loss or muscle gain. Calorie restriction is the key. OMAD and other time-restricted feeding (TRF) schemes are not the magic behind fat loss. Eat fewer calories and exercise and you recomp your body. Keto might seem really effective but that is usually an illusion. It does work if you restrict your calories. And it might seem like a magic weight loss diet but that is water weight. Keto is effective for fat loss as long as you reduce your calories.
If you want to lose weight and keep it off, reduce your calories, exercise, and reduce or cut out non-value-added calories like processed sugar, white rice, white pasta, junk foods, beer and other alcohol.
Where OMAD and TRF and fasting come into play is their actions on mTOR, GH, IGF-1, and other metabolic factors, inflammation, and hormones. I have been doing TRF (typically a 4-8 hour eating window) and/or OMAD (0.5-1.5 hour eating window) for years. But not for weight loss. My personal experience is that they are not optimum for muscle hypertrophy but I think that the benefits outweigh the muscle negatives. And the muscle negatives are not insurmountable.
And, as in many things, how you react is what is key. So if you want to lose weight and want to try Keto, try it. But watch your metrics. Keto can be dangerous if you don't make an effort to incorporate healthy foods, fiber, and micronutrients. I have tried a TRF version of Keto seven times. Each time I get a fast weight loss but it all comes back within a few days of going back to a sustainable diet. For what it's worth, my PSA has gone down 4 times, up twice, and stayed unchanged once. No big changes. Just tells me that my cancer doesn't seem to go to town on Keto (a popular bro-sci claim).
I recently added one fasting day per week. My fast is not a typical fast. My bodybuilder NMD has me on a water/protein fast to lose fat and maintain muscle. This fast isn't for cancer. If I were going to do that I would drop the protein (per my MO).
I don't know if this has anything to do with my eating habits but my Hs-CRP is 0.25-0.75. Some have lower Hs-CRP but mine is on the low end without any extra effort or focus on my part.
I'm fairly sure that my visceral fat has to do with my diet and exercise. My visceral fat is 0.26-0.49 lbs according to multiple DEXA whole-body scans. Very low for my age and weight.
Russ
1. Association of Muscle Mass with Survival after Radical Prostatectomy in Patients with Prostate Cancer
2. Exercise-induced biochemical changes and their potential influence on cancer: a scientific review: Robert James Thomas, Stacey A Kenfield, Alfonso Jimenez
3. A prospective study of physical activity and incident and fatal prostate cancer: Edward L Giovannucci, Yan Liu, Michael F Leitzman, Meir J Stamfer, Walter C Willett
4. Recreational Physical Activity in Relation to Prostate Cancer-specific Mortality Among Men with Nonmetastatic Prostate Cancer: Ying Wang, Eric J Jacobs, Susan M Gapstur, Maret L Maliniak, Ted Gansler, Marjorie L McCullough, Victoria L Stevens , Alpa V Patel
12. Acute exercise impacts AhR and PD-1 levels of CD8+ T-cells—Exploratory results from a randomized cross-over trial comparing endurance versus resistance exercise - PMC
17. Exercise-induced biochemical changes and their potential influence on cancer: a scientific review: Robert James Thomas, Stacey A Kenfield, Alfonso Jimenez
18. American Cancer Society guideline for diet and physical activity for cancer prevention - Rock - 2020 - CA: A Cancer Journal for Clinicians - Wiley Online Library
19. Sulforaphane causes a major epigenetic repression of myostatin in porcine satellite cells – PubMed (Myostatin inhibition leads to non-androgenic muscle hypertrophy)
20. Greater stimulation of myofibrillar protein synthesis with ingestion of whey protein isolate v. micellar casein at rest and after resistance exercise in elderly men – PubMed
You could be spot on about CR being the key element.
Very often, a true keto diet that is both low in net carbs and low in protein will result in significant calorie reduction, simply by virtue of the fact that one can only eat so much fat without it being accompanied by carbs and protein!
When I am doing a strict keto, I try to keep calories to about 5% net carb and 5% protein... and usually that means I don't really feel like eating more than about 1500 cal. per day. It is amazing how small the portions can be when you are strict on limiting grams of carb and grams of protein.
Main meals were big salads with avocado, pecans, kalamata olives and LOTS of EV olive oil. Also ... low-carb veggies (broc, cabbage, cukes, zukes, etc) and snacks of dried coconut and 95-100% cacao chocolate. Coffee w/ heavy cream or coconut cream.
Without varying recipes (cauliflower rice w/ rotating ingredients, etc.) and additions (veg curry w/ lime, cilantro, coconut cream, etc.) it can get boring quick. But hunger was never a problem.
Just be aware... when I say no issues with hunger, that is AFTER a period of adjustment (called "keto flu") where you might crave carbs, and generally feel crappy. That can last days, or even weeks, depending on the individual. Do some research if you pursue it, as electrolytes can be an issue, too.
For me, the easiest way to enter a state of nutritional ketosis, when transitioning from my "normal" (= high carb, high cal) diet is to simply do a water fast for a few days. Paradoxically, the less I eat the less hungry I feel, after getting through the first day. When a hunger pang hits once I am established on a keto diet, it passes quickly... this is unlike the carb cravings I experience with my regular diet, which are relentless in the fall and winter!
"CoreScan estimates the VAT (Visceral Adipose Tissue) content within the android region, VAT is a specific type of fat that is associated with several types of metabolic diseases such as obesity, metabolic syndrome, and type 2 diabetes."
MRI?:
"Visceral adipose tissue (VAT) mass, a risk factor for cardiometabolic complications of obesity, is usually measured by magnetic resonance imaging (MRI) but this method is not practical in a clinical setting. In contrast, measurement of VAT by dual-x-ray absorptiometry (DXA) appears to circumvent the limitations of MRI."
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