In Part 1 of “Biohacking Longevity: Nutrigenomic Targets with Proven Nutraceuticals,” which was published in the January issue, I discussed concepts related to “biohacking” and “longevity,” including flipping your genetic switches, longevity, gene expression and nutrigenomics. I also discussed the impact of spermidine as an evidence-based nutraceutical that helps biohack longevity. In Part 2, this article will explore other evidence-based nutraceuticals that also help biohack longevity, including phytomelatonin, black ginger extract and pasteurized Akkermansia muciniphila (AKK) postbiotic.
Phytomelatonin/Melatonin
Melatonin (also known as N-acetyl-5-methoxytruptamine) is a hormone secreted by the pineal gland.1 Melatonin’s primary role is regulation of the body’s circadian rhythm, endocrine secretions and sleep patterns.2,3 The way it works is that light inhibits melatonin secretion and darkness stimulates secretion. Therefore, at night melatonin is secreted, which initiates sleep.
Melatonin’s effects have been shown to be regulated by genes associated with circadian rhythm.4 Furthermore, melatonin has been shown to help regulate genes underlying the daily wake-sleep pattern.5 So, what does human research show that melatonin can do for sleep? A meta-analysis6 was conducted based on 19 clinical trials on melatonin. It concluded, “that melatonin decreases sleep onset latency [the time it takes to fall asleep], increases total sleep time and improves overall sleep quality. The effects of melatonin on sleep are modest but do not appear to dissipate with continued melatonin use. Although the absolute benefit of melatonin compared to placebo is smaller than other pharmacological treatments for insomnia, melatonin may have a role in the treatment of insomnia given its relatively benign side-effect profile compared to these agents.” In this meta-analysis, overall sleep quality was significantly improved in subjects taking melatonin compared to placebo (p<0.001). Other research7 has shown similar results.
Phytomelatonin: A Superior Alternative to Synthetic Melatonin
Many people are not aware that, like humans and animals, melatonin is also produced in plants (in which case, it is called phytomelatonin) and is used by them for light-dark cycles.8 Additionally, it has been proposed that plant-derived phytomelatonin represents a superior alternative to conventional synthetic melatonin. One scientific journal article9 stated that: “The interest of this proposal arose from the need to avoid the unwanted by products present in synthetic melatonin preparations. The substitution of synthetic melatonin by phytomelatonin in medical treatments could also lead to substantial improvements in the results.”
Of greater interest is a six-week, randomized, double-blind, placebo-controlled, decentralized clinical trial10 conducted using an online platform with validated questionnaires with 1,233 adult participants that have sleep problems. There were four intervention groups: 1 mg phytomelatonin from Somnatural (extracted from St. John’s wort, Nutraland USA), 3 mg phytomelatonin from Somnatural, 10 mg synthetic melatonin and placebo. Objectives included, but were not limited to, sleep problems, such as falling asleep and sleep restlessness. Results differed depending upon the cohort, but some of the findings were as follows. In a cohort of participants who already used pharmaceuticals, OTC (over-the-counter), supplements or cannabinoids to treat sleep disturbances, and who had sleep problems over the past seven days, 1 mg Somnatural phytomelatonin and 10 mg synthetic melatonin outperformed placebo (both P<0.05). In a cohort of participants (n=358) who were diagnosed with a sleep disorder worried about not being able to fall asleep in the past seven days, 1 mg and 3 mg Somnatural phytomelatonin significantly improved outcomes relative to baseline (P<0.05); 10 mg synthetic melatonin did not. In pairwise comparisons, among participants (n=1,131) who reported sleep disturbances for three months or longer and reported restless sleep in the past seven days, 3 mg Somnatural phytomelatonin provided significant improvements and outperformed 10 mg synthetic melatonin (P=0.014). In conclusion, 1 mg and 3 mg of phytomelatonin from Somnatural generally performed as well as or outperformed 10 mg synthetic melatonin and placebo for certain sleep problems in specific cohorts. Overall, high-dose synthetic melatonin offered no additional benefit compared to low-dose phytomelatonin, while all active treatment arms were safe and well tolerated.
Another 28-day study interventional, open label, pilot trial examined the effects of plant-based melatonin (phytomelatonin) from Somato tomato extract (Nutraland USA) on key physiological and psychological domains associated with sleep quality, autonomic function and health-related quality of life (HRQoL). The sample of the study included 22 healthy men and women (mean age: 42 years) receiving 2 mg of phytomelatonin daily from Somato (a tomato extract). Using a decentralized, real-world evidence (RWE) design, the study integrated objective biometric data from Oura ring wearable devices with validated participant-reported outcomes (e.g., Pittsburgh Sleep Quality Index (PSQI) and HRQoL using Short Form 36 Health Survey (SF-36)) to explore tolerability, early efficacy signals, and mechanistic trends in a healthy adult population. Compared to baseline, results showed that participants were able to fall asleep 33 percent faster (p=0.005), spent less awake (p=0.002), had better sleep efficiency (p=0.011), and had an improved global PSQI score (p=0.025). Significant improvement was also demonstrated for emotional well-being (p=0.02). In summary, this pilot study found that just 2 mg/day of phytomelatonin from Somato tomato extract improved physiological and psychological domains associated with sleep quality, autonomic function and health-related quality of life (HRQoL).
Black Ginger Extract
Black ginger (Kaempferia parviflora), also known as “Thai ginseng” or “Thai ginger,” is an herbal extract with three main areas of human research: abdominal fat reduction, physical fitness and male sexual health. As a traditional herbal medicine of Thailand, it has been used as folk medicine for many centuries to improve physical work capacity and prolong hill trekking.11 Its content of polymethoxyflavones (PMF) has been identified as being responsible for the effects of black ginger extract (BGE).12-14 This article will focus on BGE’s impact on abdominal fat reduction.
In research on mice, BGE reduced body weight gain and intraabdominal fat accumulation in mice. Nutrigenomically, BGE accomplished this by upregulated gene expression of a mitochondrial protein found in brown adipose tissue (BAT).15 Now, let’s look at the results in human research.
Human Research on Fat Reduction
Visceral fat is belly fat found deep within your abdominal cavity. It surrounds important organs, including your stomach, liver and intestines. Research suggests that if you have a potbelly—or are more “apple-shaped” than “pear-shaped”—you may have more visceral fat.
Two 12-week, randomized, double-blind, placebo-controlled clinical trials investigated the effects of BGE (providing 12 mg PMF/day) on visceral fat. One study16 was conducted in 80 overweight Japanese adults investigating the effects of BGE on visceral fat area (VFA), subcutaneous fat area (SFA) and total fat area (TFA). Results showed that VFA, SFA and TFA was significantly reduced in the BGE group compared to placebo. The other study was conducted on 76 overweight and pre-obese Japanese adults. Results were, compared with the placebo group, the BGE group exhibited significant reduction in VFA, SFA and TFA and triglyceride levels.
Recently, a 12-week interventional, single-arm, open-label, proof-of-concept pilot trial examined the effects of 12 mg of PMF daily from ACTIZ!NG BGE (Nutraland USA) on body weight, body composition and quality of life measures in 12 apparently healthy American men and women. Results were that, compared to baseline, supplementation with ACTIZ!NG led to overall decreases in waist circumference, waist-to-hip ratio, and visceral adipose tissue, alongside increases in lean mass and fat-free mass. Daily intake of 12 mg PMFs from ACTIZ!NG was well tolerated, supporting a good safety profile. Quality-of-life measures (SF-36) also showed consistent improvements across multiple domains, including physical and emotional functioning, energy, social functioning, pain and general health.
Pasteurized Akkermansia Muciniphila
Akkermansia muciniphila (AKK) is a human intestinal microorganism (i.e., probiotic). It colonizes the gastrointestinal tract of humans and other animals and can be found within the intestinal mucosal layer of intestinal epithelial cells as well as in the caecum (an area at the beginning of the large intestine).17 AKK’s primary function revolves around the degradation of mucin proteins, serving as a gatekeeper of intestinal permeability. Its prevalence can decrease with age or in the presence of disease states.18
In high-fat-diet-induced mice, pasteurized AKK improved metabolic dysregulation by preventing body weight gain after one week. Additionally, it decreased the weight of the major adipose tissues, reduced adipogenesis/lipogenesis and serum TC levels, improved glucose homeostasis (balance), and suppressed inflammatory insults. These benefits were impacted by pasteurized AKK’s downregulation of gene expression associated with inflammatory cytokines and proteins.19
Pasteurized AKK for Weight Loss
A postbiotic can be any probiotic that has been pasteurized or heat-treated, and yet still provides health benefits—a sort of zombie probiotic if you will. Although a postbiotic is not a live organism, it still provides probiotic-like effects. Such is the case with pasteurized AKK. Research from four different human clinical trials suggest that pasteurized AKK postbiotic may help facilitate weight loss.
Depommier et al. study
A three-month, randomized, double-blind, placebo-controlled trial20 examined 32 overweight/obese people with insulin resistance receiving 10 billion bacteria of live (probiotic) or pasteurized (postbiotic) AKK daily, or placebo for three months. The results were that AKK was safe and well tolerated, and pasteurized AKK was more effective than live AKK. Compared to the placebo, pasteurized AKK improved cardiometabolic parameters. Although it fell short of reaching statistical significance, pasteurized AKK supplementation decreased body weight (-2.27 kg [~5 lbs.]) as compared to the placebo group and fat mass (-1.37 kg [~3 lbs.]) and hip circumference (-2.63 cm) as compared to baseline.
You et al. study
In this randomized controlled trial,21 130 overweight participants were randomly assigned to receive a placebo, or 10 billion bacteria of either AKK probiotic (PB), or pasteurized AKK postbiotic (POST) for eight weeks. Results demonstrated that, after eight weeks of intervention, both the PB group (PB vs placebo = -0.63 vs 1.272, P < 0.001) and the POST group (POST vs placebo = -0.63 vs 0.43, P < 0.001) demonstrated significantly greater weight reduction compared to the placebo group. Notably, both the PB and POST intervention significantly reduced triglycerides (P < 0.001).
Aalipanah et al. study
An eight-week randomized, double-blind, placebo-controlled clinical trial22 compared compare the impact of daily consumption of pasteurized AKK postbiotic-fortified yogurt (AKK, 10 billion bacteria) with Lactobacillus rhamnosus postbiotic-fortified yogurt (L.rham) on the health parameters of 66 overweight and obese patients. Results were that, in the AKK group, significant reductions were observed in waist circumference (P = 0.003), waist-to-height ratio (P = 0.004), body fat percentage (P = 0.032), and appetite scores (P = 0.047) compared with the control group. However, the results indicated that L.rham-fortified yogurt did not demonstrate any beneficial impact on the health parameters.
Bruno et al. study
A 90-day randomized, placebo-controlled intervention, retrospective analysis assessed the effect of pasteurized AKK postbiotic (AKK001, 15 billion bacteria) and 150 mg of butyrate versus placebo in 60 overweight or obese participants. The AKK001 strain (the “longevity AKK strain”) is derived from a group of centenarians in Ragao, China, which has 134 centenarians per 1 million people, far exceeding the longevity standard (75 centenarians per 1 million people) prescribed by the United Nations.21 Results were that the AKK001/butyrate group showed statistically significant differences compared to the control group after one (P<0.001-0.051) and three months (P<0.000), in weight, body fat percentage, BMI, waist circumference, hip circumference, abdominal subcutaneous fat thickness (2 cm above, below, and at the umbilical level), as well as abdominal visceral fat thickness (2 cm above, below, and at the umbilical level. Likewise, the intervention group showed statistically significant differences compared to the control group after one month (P<0.001-0.011) in total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), and insulin, while their basal metabolic rate was higher. After three months of intervention, the blood glucose, total cholesterol, triglyceride, LDL-C and insulin levels of the intervention group were significantly lower than that of the control group, while the HDL-C level and basal metabolic rate was significantly higher than that of the control group (P<0.000).
Conclusion
This was the second part of a two-part article exploring the use of evidence-based nutraceuticals that help to biohack longevity. In this part, I examined the impact of phytomelatonin, BGE and pasteurized AKK postbiotic. These are just the tip of the iceberg when it comes to nutraceuticals that help to biohack longevity. Nevertheless, each of these nutraceuticals are excellent options when considering a formulation for biohacking longevity.VR
References:
1 Nurnberger JI Jr, Adkins S, Lahiri DK, et al. Melatonin suppression by light in euthymic bipolar and unipolar patients. Arch Gen Psychiatr 2000;57:572-9.
2 Brzezinski A. Melatonin in humans. N Engl J Med 1997;336:186-95.
3 Lissoni P, Barni S, Meregalli S, et al. Modulation of cancer endocrine therapy by melatonin: a phase II study of tamoxifen plus melatonin in metastatic breast cancer patients progressing under tamoxifen alone. Br J Cancer 1995;71:854-6.
4 Baser KHC, Haskologlu IC, Erdag E. Molecular Links Between Circadian Rhythm Disruption, Melatonin, and Neurodegenerative Diseases: An Updated Review. Molecules. 2025 Apr 23;30(9):1888. doi: 10.3390/molecules30091888. PMID: 40363695; PMCID: PMC12073486.
5 Buniyaadi A, Prabhat A, Bhardwaj SK, Kumar V. Role of melatonin in physiological mitigation of sleep disruption in an unnatural temporal environment. J Neuroendocrinol. 2025 Apr 23:e70035. doi: 10.1111/jne.70035. Epub ahead of print. PMID: 40268688.
6 Ferracioli-Oda E, Qawasmi A, Bloch MH. Meta-analysis: melatonin for the treatment of primary sleep disorders. PLoS One. 2013 May 17;8(5):e63773.
7 Fatemeh G, Sajjad M, Niloufar R, Neda S, Leila S, Khadijeh M. Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials. J Neurol. 2022 Jan;269(1):205-216.
8 Arnao MB, Hernández-Ruiz J. Functions of melatonin in plants: a review. J Pineal Res. 2015 Sep;59(2):133-50. doi: 10.1111/jpi.12253. Epub 2015 Jun 24. PMID: 26094813.
9 Arnao MB, Hernández-Ruiz J. Phytomelatonin versus synthetic melatonin in cancer treatments. Biomed Res Clin Prac. 2018; 3(3):1-6.
10 Pauli EK, et al. A Randomized, Blinded, Placebo-Controlled Direct to-Consumer Study of Health and Wellness Products on Sleep and Other Health Outcomes. Radicle Science. 2024; unpublished. 11 Saokaew S, Wilairat P, Raktanyakan P, et al. Clinical Effects of Krachaidum (Kaempheria parviflora): A Systemic Review. eCAM. 2017; 22(3): 413-428.
12 Yoshino S, Tagawa T, Awa R, Ogasawara J, Kuwahara H, Fukuhara I. Polymethoxyflavone purified from Kaempferia parviflora reduces visceral fat in Japanese overweight individuals: a randomised, double-blind, placebo-controlled study. Food Funct. 2021 Mar 1;12(4):1603-1613.
13 Yoshino S, Awa R, Miyake Y, Fukuhara I, Sato H, Ashino T, Tomita S, Kuwahara H. Daily intake of Kaempferia parviflora extract decreases abdominal fat in overweight and pre-obese subjects: a randomized, double-blind, placebo-controlled clinical study. Diabetes Metab Syndr Obes. 2018 Aug 28;11:447-458.
14 Matsushita M, Yoneshiro T, Aita S, Kamiya T, Kusaba N, Yamaguchi K, Takagaki K, Kameya T, Sugie H, Saito M. Kaempferia parviflora extract increases whole-body energy expenditure in humans: roles of brown adipose tissue. J Nutr Sci Vitaminol (Tokyo). 2015;61(1):79-83.
15 Yoshino S, Kim M, Awa R, Kuwahara H, Kano Y, Kawada T. Kaempferia parviflora extract increases energy consumption through activation of BAT in mice. Food Sci Nutr. 2014 Nov;2(6):634-7. doi: 10.1002/fsn3.144. Epub 2014 Jul 15. PMID: 25493179; PMCID: PMC4256566.
16 Yoshino S, Tagawa T, Awa R, Ogasawara J, Kuwahara H, Fukuhara I. Polymethoxyflavone purified from Kaempferia parviflora reduces visceral fat in Japanese overweight individuals: a randomised, double-blind, placebo-controlled study. Food Funct. 2021 Mar 1;12(4):1603-1613.
17 Aggarwal V, Sunder S, Verma SR. Disease-associated dysbiosis and potential therapeutic role of Akkermansia muciniphila, a mucus degrading bacteria of gut microbiome. Folia Microbiol (Praha). 2022;67(6):811-824. doi:10.1007/s12223-022-00973-6.
18 Iwaza R, Wasfy RM, Dubourg G, Raoult D and Lagier J-C (2022) Akkermansia muciniphila: The state of the art, 18 years after its first discovery. Front. Gastroenterol. 1:1024393.
19 Choi Y, Bose S, Seo J, Shin JH, Lee D, Kim Y, Kang SG, Kim H. Effects of Live and Pasteurized Forms of Akkermansia from the Human Gut on Obesity and Metabolic Dysregulation. Microorganisms. 2021 Sep 27;9(10):2039. doi: 10.3390/microorganisms9102039. PMID: 34683361; PMCID: PMC8538271.
20 Depommier C, Everard A, Druart C, Plovier H, Van Hul M, Vieira-Silva S et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med. 2019; 25(7):1096–1103.
21 You J, Liu W, Huang Y, et al. Akkermansia muciniphila PROBIO ameliorates overweight via gut microbiota modulation: a randomized controlled trial. Food Science and Human Wellness, 2025. https://doi.org/10.26599/FSHW.2025.9250659.
22 Aalipanah E, Askarpour M, Eskandari MH, Zare M, Famouri M, Bedeltavana A, Mohsenpour MA, Sohrabi Z. Comparing the effects of yogurt containing Akkermansia muciniphilia postbiotic with yogurt containing Lactobacillus rhamnosus postbiotic on body composition, biochemical indices, appetite, and depression scores in overweight or obese adults: A randomized, double-blind, controlled clinical trial. Clin Nutr ESPEN. 2025 May 30;68:438-446. doi: 10.1016/j.clnesp.2025.05.045. Epub ahead of print. PMID: 40451504.
Gene Bruno, DBM, MS, RH(AHG) Professor Emeritus of Nutraceutical Science, is a writer, educator and a nutraceutical scientist with more than 45 years of experience educating natural product retailers and health care professionals and formulating natural products for dozens of dietary supplement companies. He has written articles on nutrition, herbal medicine, nutraceuticals and integrative health issues for trade, consumer magazines and peer-reviewed publications. Bruno also hosts “The Vitamin Professor Podcast” brought to you by VRM Media. He can be reached at [email protected].
