Key Points:
- The combination of nicotinamide, PEA, OEA, and spermidine reduces subjective levels of cravings and hunger.
- The combo also lowers LDL cholesterol and blood glucose levels, which are risk factors for cardiovascular and metabolic aging.
Fasting, usually longer than 24 hours, can potentially treat, prevent, or delay disease and enhance longevity. However, fasting for this duration can often be infeasible or dangerous for many individuals. This has prompted scientists to determine if the cellular pathways activated by fasting can be mimicked with dietary compounds.
In doing so, researchers found that 36 hours of fasting leads to a natural elevation in four metabolites: nicotinamide, PEA, OEA, and spermidine. Moreover, supplementing with this metabolite combination extended the lifespan of nematodes, suggesting their promise in promoting longevity in humans. Subsequently, in a pilot study, the four compounds were found to be safe and tolerable, while reaping anti-inflammatory and antioxidant effects.
Now, researchers from People Science Inc., in Los Angeles, have found that the four compounds help to optimize markers of metabolic and cardiovascular health in older adults. These findings suggest that the health and longevity benefits of prolonged fasting may, at least partially, be recapitulated by supplementing with dietary compounds.
Fasting Mimetic Combo Reduces Hunger and Cravings
A total of 42 overweight individuals (average age: 62) with an HbA1c of at least 6%, indicating prediabetes, participated in the study. About half the participants received the fasting mimetic combo (nicotinamide, PEA, OEA, and spermidine) while the other half received a placebo for 8 weeks.
The participants were asked to fill out surveys assessing their hunger over the time course of the study. Overall, the participants in the fasting mimetic group showed a subjective decrease in hunger and cravings, suggesting the combo can prevent overeating. The participants in the fasting mimetic group also reported less bloating and abdominal pain. However, self-reported sleep duration, sleep quality, anxiety levels, contentedness, low mood, stress, and energy did not change.
Both obesity and prediabetes are thought to accelerate the aging process by promoting oxidative stress—damage caused to cells by excess levels of reactive molecules. Oxidative stress promotes heart disease by damaging LDL cholesterol. While LDL cholesterol itself can be used as a marker to evaluate heart disease risk, oxidized LDL (LDL damaged by oxidative stress) is a more accurate measure. Furthermore, the LDL particle number is an even more accurate measure. Remarkably, the researchers found that the fasting mimetic combo reduced total cholesterol, LDL cholesterol, oxidized LDL cholesterol, and LDL particle number.
Additionally, the researchers showed that the fasting mimetic group had lower blood glucose levels, which hints at the mitigation of prediabetes. Nevertheless, there were no significant changes in CRP, a measure of inflammation; HbA1c, a measure of long-term elevated blood glucose levels; HDL cholesterol, insulin, or triglycerides. Together, these findings suggest that the fasting mimetic combo is effective in countering several risk factors for accelerated cardiovascular and metabolic aging.
More About Each Supplement
Each of the metabolites in the fasting mimetic combo (250 mg of nicotinamide, 600 mg of PEA, 400 mg of OEA, and 8 mg of spermidine) can be purchased separately as a supplement. The contribution of each compound to the beneficial effects observed in this study is unknown, but combining all four components may potentially provide synergistic effects. Still, each compound on its own has been shown to promote health and longevity.
Nicotinamide
Nicotinamide is an NAD+ (nicotinamide adenine dinucleotide) precursor, which elevates NAD+ levels in the body. NAD+ levels have been shown to decline with age and in various pathological conditions, including diabetes and obesity. Thus, by replenishing NAD+ levels, nicotinamide could account for the effects seen in this study. Moreover, nicotinamide produces a metabolite called 1-methylnicotinamide that has been shown to reduce inflammation and mitigate heart disease.
Spermidine
Spermidine belongs to a class of molecules known as polyamines and, like NAD+, declines with age. It has been shown to extend the lifespan of yeast, nematodes, flies, and mice. One of spermidine’s primary anti-aging effects is elevating autophagy, our cellular waste and disposal system. Autophagy promotes cellular health but becomes impaired with increasing age. Spermidine has also been shown to counter other drivers of aging, such as mitochondrial dysfunction and inflammation.
Palmitoylethanolamide (PEA) and Oleoylethanolamide (OEA)
PEA and OEA are fatty acid amides, which are derived from palmitic acid (a saturated fatty acid) and oleic acid (a monounsaturated fatty acid), respectively. Fatty acid amines are diverse and primarily act as signaling molecules. While PEA has been shown to have anti-inflammatory and neuroprotective effects, OEA promotes satiety, reduces food intake, and increases fat metabolism. Thus, OEA could account for the reduced hunger and cravings associated with the fasting mimetic combo.
Can Fasting Really Be Mimicked?
It may be difficult to completely mimic the beneficial effects of prolonged fasting using dietary compounds. Fasting can have profound effects, including the activation of stem cells, which regenerate tissues. Still, certain dietary regimens appear to garner benefits similar to fasting, such as the fasting-mimicking diet, which consists of low carbohydrates, high unsaturated fats, and moderate protein. The fasting-mimicking diet reduces the potential side effects of water-only fasting, such as dizziness.
With that being said, it will likely take more than just the combination of nicotinamide, PEA, OEA, and spermidine to replicate 36 hours of water-only fasting. Fasting for this duration gives the metabolic machinery of our cells, such a mitochondrion, a break. Consuming any amount of food does not allow for this. However, considering the difficulty involved and potential side effects of prolonged fasting, taking the fasting mimetic combo may prove beneficial, particularly for overweight individuals with prediabetes.
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