Two-month period of 500 mg lecithin-based delivery form of quercetin daily dietary supplementation counterbalances CF symptoms: 2023 Rondanelli et al

[Andy]

[Approx 25% of participants had LC]

Background
Chronic fatigue (CF) is a complex phenomenon without clear etiology that may require long-term treatment, but to date, no specific therapy has been identified for it. Some botanicals might be helpful in the management of CF. Among these botanicals, quercetin demonstrates its capacity to modulate multiple biological pathways and acknowledged major properties in CF: antioxidant, anti-inflammatory, immunomodulating, improving exercise endurance, enhancing mitochondrial biogenesis, repairing mitochondrial dysfunction.

Purpose
Given this background, the aim of this study was to evaluate if a 2-month period of daily Quercetin Phytosome™ 500 mg supplementation is of benefit for the relief of CF.

Methods
The primary end point has been the evaluation of fatigue, by Fatigue Impact Scale (FIS-40). The secondary end points have been the assessment of sleep, by Pittsburgh Sleep Quality Index (PSQI), evaluation of muscle performance, by short physical performance battery and by wearable armband-shaped sensor in order to evaluate the number of steps, body composition, by DXA and quality of life by Short‐Form 12–Item Health Survey (SF‐12).

Results
Seventy-eight subjects (42 F; 36 M) (mean age 56 ± 9) reporting CF symptoms, completed the study (placebo/supplement 38/40). The FIS-40 mean difference changes between groups (supplement minus placebo) was − 10.583 points (CI95% −11.985; −9.182) (p < 0.001). Also, statistically significant changes between groups have been recorded in Pittsburgh Sleep Quality Index − 2.040 points (CI95%: −2.770; −1.309), p < 0.01), number of steps 1443.152 (CI95%: 1199.556; 1686.749), and SPPB (score) 0.248 (CI95%: 0.105; 0.391) (p < 0.001).

Conclusion
The quercetin supplementation counterbalances CF symptoms.

Open access, https://www.sciencedirect.com/science/article/pii/S0753332223012519

 

[Hoopoe]

I'm not surprised by this because it aligns with my experience. My current treatment approach includes various plant flavonoids and antioxidants and it seems to work somewhat.

 

[Ash]

I'm not surprised by this because it aligns with my experience. My current treatment approach includes various plant flavonoids and antioxidants and it seems to work somewhat.

Any particular brand or formula?

 

[boolybooly]

I find quercetin a double edge sword because I find it stimulating. In fact I have to limit my onion intake very strictly to prevent sleep stopping head buzz and migraines with a kind of quercetin hangover afterwards.

My theory is, some anti-inflammatories work by acting like, or stimulating, stress hormones, like epinephrine in some nasal asprays and guarana, caffeine also imho echinacea is like this too.

Stress hormones suppress immune activity, but this allows the cause of the immune activity to proceed unchecked.

So you get overstimulation if you have the kind of ME which makes nerves hypersensitive, which I do, then you get migraine due to lactic acid build up in the brain, then you get an immune crisis like an infection episode when it wears off due to the pathogen debt it has created which causes inflammation as the immune system tries to tackle it.

So for me it causes short term boost with payback. I would probably would not respond well to quercetin supps and have to watch my onion as I said.

I have read that the complex carbs present in Xanthan gum assist metabolic processing of quercetin so I have some of that if I have onions.

I agree antioxidants are helpful, my main approach is omega 3s, turmeric and VitD these days as these are also anti-inflammatory but not via the stress hormone / immune suppression route.

Anti-inflammatories are not all equal!

 

[Hutan]

It claims to be a double-blinded study and the size of the study is ok. There seem to be significant differences between the treatment and placebo including a large difference in an objective measure - number of steps (so long as that number of steps is a daily measure). So, on the face of it, without reading the study, it sounds interesting.

The next question is, would the investigators have a reason to be biased? Unfortunately they do.

AR and GP are employed by Indena SpA.

Two of the five authors are employed by a nutraceutical company, specifically the Development Department. The company has a range of products related to quercetin including Quercefit Quercetin Phytosome (TM) (the product used in the study), and they do use scientific studies to back up claim of benefit e.g.

Science confirms it again: Quercefit® can be a reliable ally when viral infections may threaten our immune system. The concluding phase of a recent clinical study has shown that supplementing with quercetin Phytosome® helps keep subjects’ immune system strong, providing quicker recovery and milder symptoms occurrence in the event of Sars-CoV-2 infection.2

Funding was from

The authors thank the whole partnership on the Project MIND FoodS Hub: Milano Innovation District Food System Hub: Innovative concept for the eco-intensification of agricultural production and for the promotion of dietary patterns for human health and longevity through the creation in MIND of a digital Food System Hub (P.O.R. 2014-2020_BANDO Call HUB Ricerca e Innovazione _D.G.R. NR 727 del 5/11/2018).

So, the funders are wanting to find high value uses for plants.

Of course, none of that means the study result is not true, I'd just want to see some independent verification before believing the results.

There are some alarm bells in the abstract - e.g. the vagueness of the selection criteria - chronic fatigue; the fact that not all of the outcomes are reported in Results, and the certainty of the conclusion.

 

[Hutan]

There is quercetin in food, and a healthy diet would give a person quite a lot of quercetin. But the 500 mg dose used in the study would be hard to achieve from a good diet. From what I can see, onions have a high amount of quercetin, but you have to eat 1 kg to get 300 mg. One apple is reported to have 4.4 mg. A cup of green tea contains 2.5 mg. It is said that a dose of 1 g (1000mg) or more per day can cause kidney problems. So, the study dose is in a sensible range - high enough to potentially make a difference, but not so high as to cause problems.

Yeah - selection incredibly vague - basically any unexplained chronic fatigue

A randomized, double-blind, placebo-controlled trial was conducted in subjects who complain CF symptoms. The subjects were recruited from the Dietetic and Metabolic Unit of the “Santa Margherita” Institute, University of Pavia, Italy.

Outcomes:
Primary - self-reported fatigue - Fatigue Impact Scale
Secondary-
Pittsburgh Sleep Quality Index
Body composition - several measures (fat mass, fat free mass, distribution of fat); also body weight, height, BMI
Quality of life - SF-12
Physical function - Gait speed; chair stand test; timed up and go test; short physical performance battery (sum of the three tests plus an assessment of balance)
Total steps - measured with an arm band sensor - it looks like the total steps is for a day. Baseline totals were low - about 2500 steps.

Dropouts were minimal, and the baseline data is given only for the participants who provided data at the end of the study, which is good.

The results do look impressive. In the placebo group, the step count reduced by about 200 steps. In the treatment group, the step count increased by about 1200 steps - a 47% increase. Unlike in the placebo group, BMI reduced in the treatment, moving towards the normal range.

The only weird thing I could see was that the SF-12 physical scores improved in both groups, by 7 in the placebo and 9 in the treatment group. I assume this is on the 1 to 100 scale where 100 is high functioning and 50 is normal (baseline wasn't good at around 35). But, the SF-12 mental scores reduced. At baseline they were about 44, but after the two months, the placebo group had got worse by 7 and the treatment group had got worse by 5. However, neither of the changes in the physical or mental SF-12 scores were significantly different between groups. I would have thought, if people were feeling less fatigued, and moving more and getting more things done as a consequence, then they would be feeling happier. But they didn't report that.

The discussion about why the Fatigue Impact Scale improved, but the SF-12 scores didn't is interesting

We also noted a discrepancy between the average values of the fatigue test at baseline (which are in line with the values presented in other studies, such as in the study by Castro-Marrero [6] and the values of the SF-12 test. We then considered some explanations. The main one concerns the overestimation of fatigue by patients with chronic fatigue. Already in 1996 it was reported that fatigue can be overestimated in patients with chronic fatigue [14]. This situation is confirmed in numerous subsequent studies [25]. Moreover, we also considered that the shortened version of the SF 12 test is not adequate for assessing quality of life in patients with chronic fatigue, but that the SF 36 test probably needs to be used, although other studies, albeit conducted in different settings, such as obese patients [40], [41], have demonstrated that SF-12 and the SF-36 are highly correlated, and both summary measures of the physical and mental components in the SF-12 explained about 90% of the variation in the same summary measures in the SF-36. However, no studies have demonstrated this correlation in patients with CF.

The authors do note that

Although these preliminary results are promising, they need further confirmation from large cohort studies.

So, this actually seems like a good study. My only concerns are the results seem almost too good to be true and that the study cohort probably has little relevance to people with ME/CFS, especially those with BMIs in the normal range. And of course the conflicts of interest of the authors.

 

[Ash]

I find quercetin a double edge sword because I find it stimulating. In fact I have to limit my onion intake very strictly to prevent sleep stopping head buzz and migraines with a kind of quercetin hangover afterwards.

My theory is, some anti-inflammatories work by acting like, or stimulating, stress hormones, like epinephrine in some nasal asprays and guarana, caffeine also imho echinacea is like this too.

Stress hormones suppress immune activity, but this allows the cause of the immune activity to proceed unchecked.

So you get overstimulation if you have the kind of ME which makes nerves hypersensitive, which I do, then you get migraine due to lactic acid build up in the brain, then you get an immune crisis like an infection episode when it wears off due to the pathogen debt it has created which causes inflammation as the immune system tries to tackle it.

So for me it causes short term boost with payback. I would probably would not respond well to quercetin supps and have to watch my onion as I said.

I have read that the complex carbs present in Xanthan gum assist metabolic processing of quercetin so I have some of that if I have onions.

I agree antioxidants are helpful, my main approach is omega 3s, turmeric and VitD these days as these are also anti-inflammatory but not via the stress hormone / immune suppression route.

Anti-inflammatories are not all equal!

So helpful to read your experience thanks @boolybooly

 

[darrellpf]

Quercetin is a recommended supplement for those with MCAS (Mast cell activation)

I've had very good success (way more energy, clarity) following the masc cell protocol (cutting histamines from diet, using H1 and H2 antihistamines). I've found that changing the antihistamines every few months also works very well.

We're aware that there is a large inflammatory component to ME/CFS. You see some of this in Patterson's technique of beating down inflammatory cytokines. Over the course of many years and many drugs/supplements, I've found that anything anti-inflammatory works well for sometimes months or years, then it is almost as if the 'inflammation' finds another route. I'd also say that targeting inflammation offers relief but doesn't attack the cause.

 

[boolybooly]

So helpful to read your experience thanks @boolybooly

Thanks for saying so @Ash .

I make subjective reports in the hope that people can make sense of them and these are not just meaningless obstacles faced in isolation and can help validate other people with a similar lived experience, or even help others to understand the situation we face somehow. But I am only reporting what I have observed about myself, not making recommendations, not least because I appreciate not everyone responds the same way I do to these things. So very much n=1 but still worth mentioning in a conversational way, I hope.

I refreshed my memory about quercetin and have remembered that although it reportedly has many beneficial effects, some sources say it also acts as a MonoAmineOxidase-A inhibitor or MAOi. This means it blocks the natural pathways which clear away stimulating molecules so they build up. This is similar to nutmeg, another MAOi which I also have to avoid. This is what I attribute my difficulty with it to.

Bromelaine on the other hand, which is often recommended alongside quercetin, I have no problems with at all.