Sadly, there’s no quick fix for the effects of aging or the extra pounds that sometimes (and so easily) sneak onto our waistlines. However, emerging research highlights spermidine’s potential role in weight management and overall health. This article explores the connection between spermidine, weight loss, and the mechanisms by which this naturally occurring compound may contribute to a healthier lifestyle.
The Science of Fasting and Calorie Restriction
Fasting - abstaining from or restricting food, drink, or both - has been known to have may benefits including weight loss. More importantly though, it improves health (read: waistline impact and beyond) and lifespan in most, if not all, living organisms. As we age, the risk of many diseases increases; this is called an age-associated health effect. Many of the positive health benefits are realized because calorie restriction activates cellular processes not usually stimulated when food is readily available. One such process, autophagy, plays a prominent role.
Autophagy is a recycling mechanism that “cleans up” the obsolete, damaged, or otherwise unneeded cell contents. In one study, non-obese, healthy adults who reduced their calorie intake by 15 to 25% for two years reported improved quality of life - including improved general health, sexual drive, and mood and reduced tension. They also lost an average of 7.6 kilograms of mostly body fat.
Though the benefits are many and the process is simple, fasting is not without its difficulties, discomforts, and risks. Professor Tamotsu Yoshimori from the University of Osaka, said, “Of course we know fasting induces autophagy, but…fasting also has not good effect[s] on [the] body. So, you should think about balance between [the] bad effect[s] of fasting and good effect[s].”
Calorie Restriction Mimetics: A Promising Alternative
If autophagy is beneficial and what we want to induce, but not necessarily via fasting, fasting mimetics, or foods and supplements that mimic or induce similar effects, could be the answer. Although the science is relatively new and most of the evidence available pertains to animals, the initial findings on calorie restriction mimetics (CRM) are promising. Like fasting, some CRMs activate autophagy, prolong life- and healthspan, and ameliorate a diverse array of disease symptoms.
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Spermidine: A Key Calorie Restriction Mimetic
Spermidine is naturally produced by the body, but natural levels decrease as we age. The known benefits of spermidine are many including increasing lifespan, suppressing tumor growth, enhancing your body’s immune response to cancer, and improving the heart’s ability to protect itself from disease; and these are only a few of its known effects. Spermidine is also known to induce mitophagy, a type of autophagy that eliminates damaged or dysfunctional mitochondria, the energy center of the cell, in studies of mice and human cells in culture.
Spermidine and Tumor Growth
In a study published in 2019, scientists assessed the potential of a combination of three CRMs to fight tumor growth in mice with lung cancer. They chose CRMs, including spermidine, that are known to induce autophagy and promote the body’s immune response to cancer. When compared to the control group, scientists found that the CRMs induced autophagy in the tumors and significantly reduced the number of metastases.
Spermidine and Neuroprotection
In a study published in 2021, researchers explored the ability of spermidine to confer neuroprotective effects on the brains of aging-accelerated rats and naturally aged rats. After six weeks of oral spermidine supplements, the brain tissue of the rats were analyzed. They found that spermidine up-regulated the expression of several autophagy genes (increased autophagy) and down-regulated the expression of an inflammatory gene (decreased inflammation).
Spermidine and Inflammation
In a study published in 2021, thirty healthy Japanese men ate one or two servings of ready-to-eat natto, a known dietary source of spermidine, every day for a year. When compared to a control group, that did not modify their diets, a marker that increases with inflammation, LFA-1, was reduced.
Spermidine and Obesity: A Closer Look
Obesity is associated with impaired intestinal barrier function and dysbiosis of the gut microbiota. Spermidine, a polyamine that acts as an autophagy inducer, has important benefits in patients with aging-associated diseases and metabolic dysfunction. Spermidine intake is negatively correlated with the obesity index in both humans and mice.
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Spermidine supplementation causes a significant loss of weight and improves insulin resistance in diet-induced obese (DIO) mice. These effects are associated with the alleviation of metabolic endotoxemia and enhancement of intestinal barrier function, which might be mediated through autophagy pathway and TLR4-mediated microbial signaling transduction. Moreover, spermidine causes the significant alteration of microbiota composition and function.
Spermidine, Gut Health, and Weight Loss
Spermidine preserves the integrity of gut barrier associated with autophagy induction. Studies show that spermidine alters the composition and function of the gut microbiota. Gut microbiota is required for spermidine-mediated alleviation of metabolic syndrome in DIO mice. Inhibition of TLR4 signaling contributed to anti-obesity effect spermidine. The beneficial effects of spermidine were attributable in part to the enhancement of gut barrier integrity and the alteration of the gut microbiota.
Spermidine's Impact on Metabolic Syndrome
Spermidine administration ameliorates HF diet-induced metabolic syndrome. Analyses included mice body weight, food and water intake, adipose tissue weight, glucose tolerance tests (GTTs), insulin tolerance tests (ITTs), plasma fed insulin levels, and HOMA-IR index.
Clinical Evidence: Spermidine and Obesity in Humans
In a cross-sectional study, participants who were obese had higher serum spermidine concentrations than those who were of normal weight. Compared with participants in the first quartile, those in the third and the fourth quartile had a significantly increased risk of prevalent obesity after adjustment for confounding factors.
In the follow-up study, participants in the third and the fourth quartile had significantly lower risks of an increase in BMI after adjustment for confounding factors, with the lowest quartile as the reference. Meanwhile, a nonlinear relationship between spermidine and BMI was found in the follow-up study. Serum spermidine was positively associated with increased odds of obesity in the cross-sectional study but reduced odds of an increase in BMI in the follow-up study among Chinese adults.
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Spermidine: A Multifaceted Approach to Health
Spermidine, a natural polyamine, appears to be a promising intervention for the treatment of obesity in animal studies. Spermidine in tissues can be synthesized intracellularly, ingested through the diet, or produced by the intestinal flora. Spermidine is mainly found in some specific foods, such as wheat germ, soybeans and mushrooms. Increased dietary intake of spermidine has been found to be associated with reduced all-cause mortality and the incidence of cardiovascular disease, while whole-blood spermidine levels decrease with aging, suggesting that spermidine may have health-protective effects associated with disease and aging.
Previous animal studies suggest that spermidine supplementation can help reduce body weight and improve metabolic disorders associated with obesity. In 2018, two animal studies consistently showed that spermidine supplementation caused a significant loss of weight and improved insulin resistance in high-fat diet-induced obese mice. Furthermore, spermidine also can reduce the blood lipid level in high-fat diet-induced obese mice or acute hyperlipidemia mice.
Spermidine and Cognitive Function
Cognitive decline is one of the most feared consequences of ageing, but spermidine could offer hope. A clinical trial published in Alzheimer’s & Dementia found that three months of spermidine supplementation improved memory in older adults with mild cognitive impairment. The SmartAge trial, published in GeroScience, also found improvements in memory and reductions in inflammatory markers in participants aged 60 to 90. Spermidine stimulates autophagy, which breaks down faulty proteins that otherwise accumulate in the brain and are linked to Alzheimer’s disease. This “cellular housekeeping” clears the way for neurons to function better.
Spermidine and Heart Health
Heart disease remains the world’s leading cause of death. New research suggests spermidine could also protect your heart. In aged mice, spermidine supplementation has been shown to enhance heart elasticity, reduce fibrosis (stiffening) and improve mitochondrial function, which supports energy production within cells. It mimics some of the benefits of exercise and caloric restriction. People with high spermidine intake tend to have lower blood pressure and a reduced risk of cardiovascular disease. A study from Nutrients (2024), using UK Biobank data, reported not only fewer heart attacks but a significant reduction in all-cause mortality for those with high dietary spermidine.
Spermidine and Cancer Prevention
Emerging research highlights spermidine’s potential in cancer prevention through several mechanisms. By triggering autophagy, spermidine can lower the chance of cells turning cancerous. A 2018 review in Nature Reviews Cancer found how autophagy can prevent the initiation of tumours by maintaining healthy cells in the body.
Spermidine also supports immune function, particularly by rejuvenating T cells, which are crucial for identifying and eliminating cancer cells. A 2020 study published in Nature Communications demonstrated that spermidine supplementation restored T cell function in aged mice, improving immune surveillance against tumours.
Dietary Sources of Spermidine
One of the easiest and safest ways to get more spermidine is through your diet. Some good sources include:
- Aged cheese
- Wheat germ
- Mushrooms
- Soy products
- Whole grains
- Legumes
A tablespoon of wheat germ provides around 1.2 milligrams of spermidine, and 100g of mushrooms or cheddar can offer up to 10mg.
Spermidine Supplementation
Though calorie restriction is undoubtably effective, it is also difficult and not without risk. Supplementing your diet with CRMs like spermidine can be similarly effective, definitely easier, and probably more satisfying. Spermidine can be found in many foods like the natto eaten in the above study; vegetables like green peas, corn, and pumpkin; and, perhaps easiest, can be taken as a supplement like our premium de-fatted wheatgerm supplement Primeadine®.
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