# Clinical Study: New Zealand Bitter Hops Extract Reduces Hunger During a 24 h Water Only Fast

**TYPE:** Primary Clinical Research (Peer-Reviewed)
**STATUS:** Published
**TRIAL REGISTRY ID:** ACTRN12619000454178 (Australian New Zealand Clinical Trials Registry)
**ETHICS APPROVAL:** Southern Human Ethics Trial Board (18/STH/267)
**DOI:** [10.3390/nu11112754](https://doi.org/10.3390/nu11112754)
**JOURNAL:** Nutrients (2019, Vol 11, Issue 11)
**AUTHORS:** Walker et al. (The New Zealand Institute for Plant and Food Research)
**CONFLICT OF INTEREST STATEMENT:** Authors declare no competing financial interests. Funded by PFR internal sources.

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## Study Summary (TL;DR)
This clinical trial investigated whether Amarasate® (a bitter hops extract) could reduce hunger during a 24-hour water-only fast. Thirty men fasted for 24 hours once a week for three weeks. They were given either a Placebo, Low Dose (250mg), or High Dose (500mg) of Amarasate at 16 hours and 20 hours into the fast.
**Key Finding:** Both Low and High doses significantly reduced hunger (>10% reduction) compared to placebo. The "lunchtime hunger spike" observed in the placebo group was completely absent in the Amarasate groups.

## Full Text Content

### 1. Introduction
A healthy diet helps to prevent many chronic diseases prevalent in the Western world, as well as being associated with greater longevity and an improved quality of life [1,2]. Modern excesses in the Western diet have resulted in increased rates of diet-linked disease such as obesity, diabetes, cancer, and cardiovascular disease (CVD) [3–6], and are associated with unfavorable perceptions of mental state, health, vitality, and physical function [7,8]. To counter these negative health outcomes, dietary interventions are often prescribed as an initial treatment therapy, with many current diet strategies reliant on alterations of macronutrient make up, that typically modify diet composition and impose food choice restriction [9]. While effective if adhered to, more highly restrictive diets are associated with poor compliance that may ultimately result in diet failure, and suggest the potential for alternative diet strategies [10,11].

In contrast to many conventionally prescribed diets, intermittent fasting (IF) does not require changes in food choice or diet composition, instead relying on either time-restricted eating [12], recurrent reduction in daily caloric intake [13], or complete water-only fasting days [14], and hence may be an alternative diet option when conventional diets fail. Contemporary research suggests that IF may offer equivalent health benefits compared with classically prescribed diets [15–23]. Additionally, IF confers benefits that extend well beyond weight loss. It replicates some health benefits associated with prolonged caloric restriction [16,24], is immunoregulatory [25], effects markers of skin health and dermatology [26–28], improves symptoms of arthritis [29], is associated with improved outcomes for cancer patients [30], and enhances glucose regulation post-fast [31]. While diet composition is not modified during fasting, feelings of hunger are increased [32,33], notably during the 16–24 h period of a 24 h water-only fast [34], that may negatively affect dietary restraint and potentially reduce long- and short-term compliance to the diet regime [35–38].

Indeed, traditional medicine records a history of using bitter appetite suppressants to alleviate hunger during times of fasting [39,40], with recent studies showing bitter compounds to be effective anorexigenic agents [41,42]. Hops bitter acid derived compounds reduce body weight, fat mass and improve glucose homeostasis in humans, while also stimulating the release of anorexigenic gastrointestinal (GI) peptide hormones in both human cell lines and in animals [43–45]. We hypothesize that consumption of a bitter hops extract will reduce subjective ratings of appetite during a water-only fast day.

In this study, we examined the effect of an extract of New Zealand Hops (Amarasate®) on subjective measures of appetite during the 16–24 h period of a 24 h water-only fast in healthy normal weight men.

### 2. Materials and Methods

**2.1. Participants**
Thirty healthy men (eligibility: age 18–55 year, BMI 20–25 kg/m²) were recruited. Potential participants were excluded if they met any of the following criteria: Current participation in a weight loss program, diagnosed diseases of the gastrointestinal (GI) tract, previous GI surgery, diabetes, or use of medication that may alter body composition. All subjects provided written informed consent.

**2.2. Study Design, Supplements and Protocol**
This was a randomized, double-blind cross-over treatment study.
* **Treatments:**
    * **High Dose (HD):** 500 mg Amarasate hops extract (250 mg x 2 capsules).
    * **Low Dose (LD):** 200 mg Amarasate hops extract (100 mg x 2 capsules).
    * **Placebo:** Canola oil excipient (0 mg Amarasate).
* **Protocol:** Participants fasted for 24 hours (18:00 to 18:00). Capsules were administered twice: once at 16 hours (10:00 AM) and again at 20 hours (2:00 PM) into the fast.
* **Appetite Assessment:** Subjective measures were recorded using 100 mm Visual Analogue Scales (VAS) [50–54].

### 3. Results

**3.1. Participants and Demographics (Table 2)**
Thirty participants completed all three treatments of the appetite trial. All participants were lean healthy males.

| Characteristic | Value |
| :--- | :--- |
| **Participants (n)** | 30 |
| **Age (years)** | 24 ± 6 (Range: 18–40) |
| **BMI (kg/m²)** | 23.1 ± 1.4 (Range: 20–24.9) |
| **Body Weight (kg)** | 72 ± 7 |
| **Ethnicity Breakdown** | Caucasian (19), Chinese (3), Persian (2), South American (2), NZ Maori (1), Sri Lankan (1), Filipino (1), Malaysian (1) |

**3.2. Composition and Stability of Treatments (Figure 3)**
The capsules contained primarily bitter α- and β-hops acids (Cohumulone 21.08%, Humulone 22.25%, Adhumulone 8.15%, etc.).
**Stability Analysis:** HPLC chromatograms of the High Dose (HD) and Low Dose (LD) capsules taken at the start of the trial vs. the end of the trial showed identical spectral profiles [47,48]. This confirms there was no degradation of the active bitter compounds during the study period.

**3.3. Appetite Ratings: Hunger (Figure 4)**
The primary outcome was subjective hunger rating.
* **Placebo Response:** The placebo group recorded a steady increase in hunger throughout the day, rising by **31.5 mm** over the 16–24 h fasting period.
* **Amarasate Response:** Both HD and LD treatment groups exhibited significantly lower hunger ratings compared to placebo.
* **Key Data Points:**
    * **Magnitude:** Differences >10 mm (considered biologically significant [59]) were recorded for the HD group relative to placebo from t=90 min onwards.
    * **Lunchtime Spike:** The placebo group showed a distinct spike in hunger at 12:00 PM. This spike was significantly blunted/absent in both Amarasate groups.
    * **Statistical Significance:** The reduction in hunger was statistically significant (p < 0.05) for both doses compared to placebo.

**3.4. Appetite Ratings: Fullness**
High Dose (HD) treatment resulted in significantly higher fullness ratings (>10 mm increase relative to placebo) from t=120 min to t=480 min.

**3.5. Side Effects**
* **Nausea:** Post-treatment nausea VAS scores did not exceed 10 mm in any group (negligible).
* **Digestive:** Liquid loose bowel movements were reported by 3 participants (HD) and 1 participant (LD). This is a known, transient effect of bitter compound regulation of colonic anion secretion [55].

### 4. Discussion
Traditional medicine records bitterness being used at times of food scarcity to reduce hunger and alleviate fast-related adverse effects [39,40], with recent research attributing this bioactivity to GI responses to bitterness [56]. This current study highlights for the first time that prolonged anorexigenic effects of GI-targeted bitter compounds may be independent of food intake, and demonstrates the capacity for non-nutritive appetite suppressant co-therapy to enhance satiety during fasting.

The mechanisms through which Amarasate affects hunger and fullness are most likely associated with anorexigenic gut peptides glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), and peptide tyrosine tyrosine (PYY). These peptide hormones are released during intestinal exposure to bitterness, and increase meal initiated satiation and enhance postprandial satiety [42,44]. It is therefore possible that these same peptide hormones may be responsible for the reduced hunger observed during this fasting trial [68–70].

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