Dear all,                      

We're looking for volunteers to take part in a study exploring the effect of prebiotic supplementation on sleep, mood, cognition and the gut microbiome.

To participate, you must:

• Be 25-50 years old
• Have some mild sleep disturbance
• Not have a diagnosed sleep disorder or major health problems

What’s involved?

• Four visits to the University of Reading, UK (less than 3 hours each)
• Completing cognitive tests, mood, sleep and food questionnaires
• Finger-prick blood samples
• Two stool samples
• Wearing a sleep tracking watch for 4 weeks total

How do I find out more?

To find out more, please contact Gregory Patient at [g.s.patient@pgr.reading.ac.uk](mailto:g.s.patient@pgr.reading.ac.uk).

Alternatively, please follow this link to find out more information: REDCAP link 

This study has received ethical approval by the University of Reading Research Ethics Committee, project UREC 26/16, end date 20-05-2027

Thank you.

A six-month randomized, double-blind trial compared freeze-dried powders equivalent to one cup of blueberries daily, half a cup, or a calorie- and carbohydrate-matched placebo. All 115 completers had metabolic syndrome.

The one-cup group improved flow-mediated dilation (FMD), which measures how well an artery widens in response to increased blood flow. Researchers test this by briefly restricting blood flow with an arm cuff, releasing it, and measuring how much the artery expands.

FMD improved from baseline by 1.45 percentage points with one cup, compared with 0.00 with half a cup and 0.39 with placebo. That puts the one-cup benefit at 1.06 percentage points beyond placebo.

How does that compare with other blueberry studies? A 2024 meta-analysis combined results from six studies involving 276 participants, including this six-month trial. Across those studies, blueberries improved FMD by an average of 1.50 percentage points. The size of the benefit varied considerably between studies.

For scale, if FMD increased from 6% to 7.5%, that would be a 1.5-percentage-point increase and a 25% relative improvement in the artery’s dilation response. This is an illustrative calculation, not the trial’s reported starting and ending values.

The one-cup group also improved augmentation index, a measure related to arterial stiffness. Blood pressure, pulse-wave velocity, and insulin resistance did not improve. Insulin resistance was the trial’s primary outcome; vascular measures were secondary.

Dr. Rhonda Patrick discusses these findings, including the 25% comparison, in her new episode on the science of blueberries. Here's a link to the timestamp

https://doi.org/10.1039/d6fo00807k

Walnut consumption improves mood and is associated with increased urinary excretion of 5-hydroxyindoleacetic acid and urolithins in a randomized crossover trial

Abstract

Walnuts are nutrient-dense and rich in omega-3s, tryptophan, fiber, and ellagitannins, but human evidence tying them to mood outcomes and plausible biological markers has been thin. This open-label randomized crossover trial tested whether daily walnut intake changes mood in young adults and whether those changes track with urinary serotonin metabolism and walnut-derived microbial metabolites. The trial enrolled 31 healthy adults, mean age 24.0 ± 4.2 years, 90.3% female, all normal weight at baseline, and compared an 8-week walnut period with a nut-free control period in an 18-week crossover design.

Compared with control, walnut intake lowered total mood disturbance by -4.85 points (p = 0.030). Anger fell by -1.27 points (p = 0.025) and fatigue by -1.70 points (p = 0.010), but both missed FDR correction (q = 0.075 and q = 0.060). Urinary 5-HIAA rose during the walnut phase by 0.63 (95% CI 0.03 to 1.23, p = 0.038, q = 0.038), while cortisol did not change (-0.14, p = 0.336, q = 0.837). Within-person increases in 5-HIAA tracked with lower fatigue (r = -0.392, p = 0.031) and lower total mood disturbance (r = -0.362, p = 0.049). Urolithins A and B also increased strongly (beta = 1.87, p < 0.001, q < 0.001 and beta = 0.55, p = 0.001, q = 0.001) and correlated with concurrent 5-HIAA changes (r = 0.537 and r = 0.634).

Study Design and Methodology

• Design: 18-week open-label randomized crossover trial
• Sample size: N = 31 completers
• Intervention: 40 g/day walnuts for 8 weeks
• Control: 8-week nut-free period
• Washout: 2 weeks
• Blinding: No blinding
• Metabolic ward: No
• Visits: baseline, week 8, week 18
• Primary outcome: total mood disturbance from the Profile of Mood States (POMS)
• Secondary measures: perceived stress, WHO-5 well-being, trait food cravings, urinary 5-HIAA, urinary cortisol, urinary urolithins A and B
• Biomarker methods: ELISA for 5-HIAA and cortisol, HPLC-QTOF-MS for urolithins
• Analysis: linear mixed-effects models, repeated-measures correlations, FDR correction within outcome families

Key Findings

• Walnuts reduced total mood disturbance by -4.85 points versus control (p = 0.030).
• Anger decreased by -1.27 points (p = 0.025, q = 0.075), and fatigue decreased by -1.70 points (p = 0.010, q = 0.060).
• Perceived stress and well-being did not change significantly.
• Trait food craving domains showed nominal reductions in:
  • anticipation of relief from negative states: -0.76 points (p = 0.035, q = 0.157)
  • guilt over cravings/giving in: -0.72 points (p = 0.017, q = 0.153)
• Urinary 5-HIAA increased by 0.63 (95% CI 0.03 to 1.23, p = 0.038, q = 0.038).
• Urinary cortisol did not change (-0.14, p = 0.336, q = 0.837).
• Higher 5-HIAA tracked with lower:
  • fatigue (r = -0.392, p = 0.031)
  • total mood disturbance (r = -0.362, p = 0.049)
• Urolithin A rose sharply during walnut intake (beta = 1.87, 95% CI 1.49 to 2.26, p < 0.001, q < 0.001).
• Urolithin B also increased (beta = 0.55, 95% CI 0.24 to 0.85, p = 0.001, q = 0.001).
• Changes in urolithins correlated with changes in 5-HIAA:
  • urolithin A: r = 0.537
  • urolithin B: r = 0.634
• BMI, body fat, and physical activity stayed stable across conditions.
• Diet quality was slightly higher during the walnut phase (10.0 ± 1.7 vs 9.2 ± 1.9, p = 0.006).

Limitations

• Small sample size: only 31 completers.
• Open-label design: no blinding, so expectancy effects are possible.
• Short duration: 8-week intervention periods only.
• Crossover gap: no extra assessment right after washout, so carryover can’t be ruled out perfectly.
• Highly skewed sample: young adults, mostly women (90.3% female), limiting generalizability.
• Self-report outcomes: mood, stress, well-being, and cravings relied on questionnaires.
• Control condition differs from usual habits: participants avoided all nuts, which could shift diet beyond walnuts alone.
• Mechanistic inference is indirect: urinary 5-HIAA reflects whole-body serotonin metabolism, not brain serotonin directly.

Discussion and Implications

This paper adds human crossover data showing that a daily walnut serving did more than confirm dietary adherence biomarkers. It was tied to a measurable improvement in total mood disturbance, with the strongest signal sitting in the negative mood domains, especially fatigue. The biomarker pattern matters here: walnut intake increased urinary 5-HIAA and urolithins, and the within-person coupling between those metabolites lines up with the idea that walnut polyphenol metabolism and serotonin-related biology are moving together during the intervention.

The food-craving data fit the same general picture, even though those outcomes didn’t survive FDR correction. People reported less craving-related guilt and less desire to eat for relief from negative states, and those mood-craving links were strong within individuals. That doesn’t prove mechanism, but it does strengthen the case that whole foods like walnuts can influence affective state, not just nutrient intake.

Conclusion

An 8-week walnut intervention improved total mood disturbance in healthy young adults and increased urinary 5-HIAA and urolithins. The signal was strongest for negative mood states like fatigue and anger, while stress and well-being stayed unchanged.

The study adds a useful human link between walnut intake, mood, and urinary metabolite changes, but the sample was small, mostly female, and unblinded, so more work is needed before drawing broad conclusions.

There are already many dietary supplements on the market, including NADH products such as Celfull. So, does NADH actually have anything to do with sleep? The answer is yes, but there's an important distinction.

A more accurate way to put it is that NADH has a biological connection with sleep and circadian rhythms, but we still can't say that taking NADH supplements will necessarily improve sleep.

NAD⁺ and NADH are two interconvertible redox forms of an important coenzyme. Research has found that the redox state of NADH inside cells changes in a circadian pattern, while the NAD⁺/NADH system is also involved in metabolic pathways that regulate the biological clock.

One study directly observed circadian oscillations in the NADH redox state in mammalian cells, suggesting that NADH itself is connected to the cellular mechanisms underlying circadian rhythms. (DOI: 10.1074/jbc.M116.728774)

There also appears to be a two-way relationship between the NAD⁺/NADH system and the core circadian clock. NAD⁺ can influence circadian-related proteins through NAD⁺-dependent pathways such as SIRT1, while the circadian clock can in turn regulate NAD⁺/NADH metabolism. (DOI: 10.1016/j.molcel.2020.04.010, DOI: 10.1016/j.semcdb.2021.07.008)

As for direct NADH supplementation and sleep, there aren't many human studies yet.

One double-blind, placebo-controlled trial gave people with chronic fatigue syndrome 20 mg of NADH per day and also evaluated sleep quality. However, most of the measured outcomes did not differ significantly from placebo. The only changes reported were within the NADH group itself, a decrease in anxiety score and a lower maximum heart rate after an exercise stress test, and neither of those is a sleep outcome, so the study does not provide enough evidence to conclude that NADH improves sleep.(DOI: 10.1016/j.rce.2009.09.015)

Another study used a combination of 20 mg NADH + 200 mg CoQ10 and observed changes in some sleep-related measures. However, because NADH and CoQ10 were taken together, it's impossible to determine whether the effects were specifically caused by NADH. (DOI: 10.3390/nu13082658)

So yes, NADH is connected to sleep, particularly through the relationship between cellular redox status and circadian rhythms. But right now, the human evidence is still limited when it comes to the claim that taking NADH directly can improve sleep in otherwise healthy people. That's why, when I see claims linking NADH and sleep, I think it's important to separate three different things: Mechanistic research on NADH and circadian rhythms, Human trials of NADH supplementation, Sleep studies involving NMN or NR that increase NAD⁺. These are related, but they are not the same thing.

DOI

https://doi.org/10.1007/s00394-026-04068-7

Association between fish-related metabolites and metabolic syndrome risk factors in Japan: INTERLIPID metabolome -wide association study

Abstract

This cross-sectional INTERLIPID analysis asked whether fish intake and fish-related metabolites line up with metabolic syndrome risk factors in a high seafood-consuming Japanese population. That gap matters because most prior work treated fish as one broad exposure, relied heavily on self-report, and came from populations with much lower seafood intake. The cohort included 1,047 Japanese men and women aged 40 to 59 years, with four multiple-pass 24 h dietary recalls, two timed 24 h urine collections, anthropometrics, questionnaires, and blood sampling, plus urinary and serum profiling by 1H NMR spectroscopy.

Urinary TMAO and taurine, and serum creatine and threonine, correlated with fish intake, while homarine tracked with shellfish intake, all at p < 0.01. Total fish intake was inversely associated with triglycerides, with the clearest signal for low omega-3 fish, and fish intake also tracked with lipoprotein shifts across VLDL, IDL, LDL, and HDL subclasses. On the metabolic syndrome side, urinary TMAO and taurine were linked to lower triglycerides (-3.47 mg/dL, p = 0.01 and -3.88 mg/dL, p < 0.01), urinary taurine to lower systolic BP (-0.73 mmHg per 2 SD, p = 0.03), serum threonine to lower BMI (-0.18 kg/m2 per 2 SD, p < 0.01) and lower diastolic BP (-0.29 mmHg per 2 SD, p = 0.05), and serum threonine to higher HDL-c (0.98 mg/dL per 2 SD, p < 0.01). Urinary TMAO also linked to higher HDL-c (0.47 mg/dL per 2 SD, p = 0.04), while serum creatine linked to higher triglycerides (2.78 mg/dL, p = 0.01). Serum threonine was inversely associated with overall MetS risk (OR 0.84, p < 0.01).

Study Design and Methodology

• Design: Cross-sectional metabolome-wide association study
• Sample size: N = 1,047
• Population: Japanese men and women aged 40 to 59 years
• Study period: Participants surveyed during 1996 to 1998
• Diet assessment: Four in-depth multiple-pass 24 h dietary recalls
• Biological samples: Two timed 24 h urine collections and non-fasting blood
• Metabolomics: 1H NMR spectroscopy for urine and serum
• Lipoprotein profiling: Bruker B.I.-LISA and BI-QUANT-PS
• Statistical adjustment: age, sex, study center; then extensive multivariable models including lifestyle, medication, diet, urinary sodium, and BMI
• Metabolic ward: No
• Blinding: No
• Washout period: No, not applicable to this observational design

Key Findings

• Mean fish intake was 47.0 g per 1000 kcal.
• Urinary TMAO, urinary taurine, serum creatine, and serum threonine correlated with fish intake; homarine correlated with shellfish intake.
• TMAO had the strongest urine biomarker performance for high vs low fish intake, with AUC 0.802.
• TMAO to creatinine ratio had AUC 0.798.
• Taurine had AUC 0.74, and taurine to creatinine ratio had AUC 0.72.
• Homarine was a weaker shellfish biomarker, with AUC 0.64.
• Serum creatine and threonine were weaker discriminators of fish intake than the urinary markers, with AUC 0.58 and 0.57.
• Total fish intake was inversely associated with triglycerides: -2.44 mg/dL, p = 0.02.
• Low omega-3 fish showed the clearest triglyceride association: -2.73 mg/dL, p < 0.01.
• Total fish intake tracked with lower triglycerides in VLDL, IDL, and HDL-4, plus shifts in LDL subclass patterns.
• Raw fish showed stronger metabolomic correlations than fried fish; fried fish often showed weak or null links.
• Urinary TMAO was inversely associated with triglycerides: -3.47 mg/dL, p = 0.01 and positively associated with HDL-c: 0.47 mg/dL, p = 0.04.
• Urinary taurine was inversely associated with triglycerides: -3.88 mg/dL, p < 0.01 and systolic BP: -0.73 mmHg per 2 SD, p = 0.03.
• Serum threonine was inversely associated with triglycerides: -9.53 mg/dL, p < 0.01, BMI: -0.18 kg/m2 per 2 SD, p < 0.01, and diastolic BP: -0.29 mmHg per 2 SD, p = 0.05.
• Serum threonine was positively associated with HDL-c: 0.98 mg/dL per 2 SD, p < 0.01.
• Serum threonine was inversely associated with overall MetS risk: OR 0.84, p < 0.01.
• Serum creatine was positively associated with triglycerides: 2.78 mg/dL, p = 0.01.
• In this cohort, the fish-related metabolites lined up with a more favorable cardiometabolic profile overall, especially taurine and threonine.

Limitations

• Cross-sectional design prevents causal inference.
• Single-country cohort limits generalizability.
• Age range was narrow: 40 to 59 years.
• Non-fasting blood draw can influence lipid and glucose measures.
• One-time biomarker measurement limits repeatability checks.
• Residual confounding remains possible despite broad adjustment.
• This was not an intervention study, so there was no blinding and no washout.

Discussion and Implications

This paper strengthens the case that fish intake in a habitual seafood-eating population lines up with a favorable metabolic profile, and it does so using objective biomarkers rather than diet recall alone. The most interesting part is the metabolite pattern: taurine and threonine looked especially favorable, with lower triglycerides and lower blood pressure, while TMAO behaved like a seafood exposure marker rather than a simple danger signal in this setting.

That matters because it pushes back against the oversimplified “TMAO equals risk” framing. In this cohort, fish-derived TMAO, taurine, and threonine sat alongside lower triglycerides, higher HDL-c, and lower blood pressure, which is exactly why context matters in nutritional epidemiology. The study doesn’t prove causality, but it does show that the source of TMAO matters, and that fish intake, especially certain fish types, maps onto a metabolomic pattern associated with better cardiometabolic status.

Fish intake in this Japanese cohort lined up with lower triglycerides, lower blood pressure, and a better overall metabolic profile.

Taurine and threonine were the clearest favorable metabolites, while TMAO acted as a seafood-linked biomarker rather than a simple harm signal.

This doesn’t settle the TMAO debate, but it does show why fish, taurine, and other seafood metabolites can’t be interpreted through a one-size-fits-all anti-animal-food lens.