4 new supplements that may not be on your radar

By Naveed Saleh, MD, MS
Published August 12, 2021

Key Takeaways

Supplements continue to sizzle, according to the results of an annual survey conducted by the Council for Responsible Nutrition. About 73% of Americans report taking them—and although that's down from 77% during the high point in 2019, it still reflects an overall upward trend since 2015. Moreover, two of five supplement users switched up their supplement routine during the pandemic, with 91% increasing intake in some fashion.

Most of us are familiar with the most common supplements like magnesium, vitamin C, iron, B vitamins, and fish oil, among others, which can enrich and fortify the body in key areas where diet-based nutrients are lacking. 

However, there are a number of new dietary supplements on the scene. Here’s what the research says about four of them. 


Found in beets, broccoli, grains, spinach, and shellfish, betaine goes by the other names of betaine anhydrous or trimethylglycine (TMG). Betaine is endogenous to the body and plays a role in liver function, cellular division, and the formation of carnitine. 

Those interested in supplements, however, have taken note of betaine’s ability to decrease homocysteine levels. The FDA has approved betaine as an oral solution to treat a genetic condition called homocystinuria.

According to Mount Sinai, scientists have suggested “betaine as a way to lower homocysteine levels in people who don’t have the genetic disease. This is because higher levels of homocysteine are associated with heart disease and stroke. But researchers don't yet know exactly how high levels of homocysteine and heart disease are related. It’s unclear as to whether homocysteine itself is harmful, or whether it is just an indicator of increased risk for heart disease.”

Betaine supplements are manufactured as a byproduct of beet processing and are available in powder, tablet, and capsule form. Recommended dosages of betaine vary based on the health condition targeted, and this supplement is usually taken with folic acid, vitamin B6, and vitamin B12. Researchers at Mount Sinai also cited preclinical research in rats that indicated that betaine may protect against harmful fatty deposits in the liver, which are due to alcohol misuse, diabetes, and obesity. They also cited one study indicating protection against lung cancer and the adverse effects of smoking, as well as a second study indicating protection against breast cancer risk.


This compound occurs naturally in honey and sugar cane. It is similar to glucose, has a low glycemic index, and is tooth-friendly, which is why it is often used in the food industry as a sugar alternative. 

To date, in vitro experiments have suggested that isomaltulose facilitates the growth of probiotics and the production of short-chain fatty acids (SCFAs). In a 2021 in vivo study published in Molecules involving rats, research indicated that isomaltulose moderates gut microbiota and the production of SCFAs and secondary bile acids in rats, which supports the use of isomaltulose as a prebiotic. 

SCFAs, such as acetic acid, propionic acid, and butyric acid, play a major role in the maintenance of the host–gut homeostasis and health status. According to the authors, “The mechanisms underlying SCFAs may be: (a) SCFAs decrease inflammatory responses, modulate the immune system, and induce apoptosis of cancer cells; (b) SCFAs, in turn, regulate gut microbial composition by inhibiting the conditioned-pathogen growth; (c) emerging research shows that SCFAs may promote the gut–brain communication, which thereby affects multiple neurochemical pathways.”

Secondary bile acids (SBAs) derive from the conversion of primary bile acids by gut microbiota. An emerging corpus of research has demonstrated that SBAs may have varied roles in host health. The authors noted that “deoxycholic acid (DCA) and lithocholic acid (LCA) have demonstrated to suppress the proliferation of Clostridium difficile, induce hepatocellular carcinogenesis, and regulate metabolic and immune responses. Moreover, DCA and LCA can be further modified into additional SBAs by intestinal microbiota, ie, hyodeoxycholic acid (HDCA). HDCA is suspected to have high cytotoxicity and anaphylactic roles. Whereas several studies reported that HDCA prevents gallstones and atherosclerosis.” 


Strains of this bacteria are ubiquitous in nature and occur in soil, air, fermented foods, and the gut. In spore form, Bacillus probiotics can tough it out in extreme environmental conditions that kill other bacteria.

According to the authors of a review published in Food Sciences and Biotechnology, “Both spore and vegetative forms of Bacillus species have been used as probiotics, and they have high stability to the surrounding atmospheric conditions such as heat, gastric conditions, and moisture. The commercial Bacillus probiotic strains in use are B. cereusB. clausiiB. coagulansB. licheniformisB. polyfermenticusB. pumilus, and B. subtilis. These strains have antimicrobial, anticancer, antioxidant, and vitamin production properties. However, Bacillus probiotics can also produce toxins and biogenic amines and transfer antibiotic resistance genes; therefore, their safety is a concern.”

5‐aminolevulinic acid

The compound 5‐aminolevulinic acid (5-ALA) is an endogenous nonprotein amino acid and is the first in the porphyrin synthesis pathway resulting in heme synthesis. It is present in nearly all cells and integral in the processes of mitochondrial activity, ATP production, and energy metabolism. Various foods contain 5-ALA, including green peppers, shiitake mushrooms, tomatoes, bananas, and ground beef.

As a supplement, 5-ALA may be helpful with respect to diabetes. In a study published in Clinical and Translational Science involving 154 participants with prediabetes who were 40-70 years of age, researchers found that in those taking 5-ALA supplements for 12 weeks, post-OGTT glucose levels and hemoglobin A1C levels declined significantly. The results of this study concur with other research indicating the antidiabetogenic effects of this agent.  

Intriguingly, 5-ALA may also synergize with PD-1/PDL-1 blockade, which is a ground-breaking immunotherapy used to treat non-small cell lung cancer, Hodgkin lymphoma, and hepatocellular cancer.

“Aminolevulinic acid/SFC combined with PD‐1/PD‐L1 blockade therapy can enhance the T cell functions and increase the mitochondrial functions to reverse T cell exhaustion. 5‐aminolevulinic acid/SFC combined with PD‐1/PD‐L1 blockade therapy could improve the T‐cell effector function and prevent cancer from evading the immune system,” wrote the authors of a study published in Cancer Science.

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