Can 'Marmite chemical' aid the heart?

“Eating Marmite can help heart attack victims live longer,” the Daily Mail has reported. The newspaper said that a derivative of vitamin B1 speeds up the healing of tissue following heart damage and that the substance, called benfotiamine, can prevent heart failure as a complication of diabetes.

The news is based on an animal study that researched how diabetic and non-diabetic mice recovered after a surgically-induced heart attack. Scientists found that diabetic mice, which could not produce insulin, had worse outcomes after heart attack. However, supplementing the mice’s diet with benfotiamine improved survival in both mice groups and had positive effects on heart function in the diabetic mice prior to the surgery.

This was useful but preliminary research done in a small number of mice. Therefore, much further work is needed to ascertain whether similar effects would be seen in diabetic and non-diabetic humans. In this experimental study, the mice were given pure benfotiamine. It is not clear whether the amount of vitamin B1 typically provided by supplements or diet, even for huge fans of Marmite, would be sufficient to have any effect in humans.

Where did the story come from?

The study was carried out by researchers from the University of Bristol and was funded by Diabetes UK and RESOLVE (Resolve Chronic Inflammation and Achieve Healthy Aging). The study was published in the peer-reviewed Journal of Molecular and Cellular Cardiology .

The Daily Mail provided brief coverage of this research and focused on foods that were rich sources of vitamin B1. While this most recent research looked at recovery following induced heart attack, the newspaper also referred to a second research article published by the same group earlier in the year that had looked at how benfotiamine supplementation affected the risk of heart failure in a mouse model of diabetes.

What kind of research was this?

This was an animal study that looked at whether a chemical similar to vitamin B1, called benfotiamine (BFT), could protect diabetic and non-diabetic mice after they were induced to have a heart attack.

The researchers say that patients with diabetes have a poorer outcome after a heart attack and that diabetes may affect the structure of the heart. They also say that a biochemical pathway called the ‘pentose phosphate pathway’ can help to protect the heart as it contracts, as well as neutralising free radicals produced when a person has a heart attack, which may damage the heart tissue. They suggest that in diabetes an enzyme in this pathway, called transketolase, is impaired. Benfotiamine is known to activate the transketolase enzyme.

What did the research involve?

Eight-week-old mice were made diabetic using a chemical called streptozotocin, which is toxic to the insulin-producing cells of the pancreas. In effect, this made the mice similar to type 1 diabetics, who cannot produce insulin. (Type 2 diabetics, on the other hand, have reduced sensitivity to the effects of the insulin their body produces.) Four weeks later these mice and non-diabetic control mice were randomly allocated to receive either 70mg/kg body weight per day of BFT or a placebo. A further four weeks later the mice either received an operation to mimic a heart attack (by blocking an artery in the heart) or a sham operation.

The researchers compared the heart function of the diabetic and non-diabetic mice, the activity of enzymes in the pentose phosphate pathway and any heart damage from free radicals. For the biochemical analysis the researchers looked at five mice in each group.

In addition to the animal study, the researchers looked at human heart cells grown in cell culture. The heart cells were starved of oxygen as would happen in a heart attack. The researchers looked at the biochemical response of the cells to this impairment under normal conditions and when they had been treated with BFT.

What were the basic results?

The researchers found that two weeks after the induced heart attack, 25% of the diabetic mice survived compared with 50% of the non-diabetic controls. Treatment with BFT improved the survival rate of both non-diabetic (80%) and diabetic mice (50%) as compared with the placebo-treated group (p<0.001).

The researchers found differences in heart function between the diabetic and non-diabetic mice, both before and after the operation:

• Before the operation BFT improved the heart’s diastolic function (where the heart fills up with blood between beats) in diabetic mice.
• BFT prevented deterioration of heart function after the operation in both diabetic and non-diabetic mice.
• BFT also prevented tachycardia (racing heart beat) in the diabetic mice after the operation.
• Both diabetic and non-diabetic animals also had improved blood pressure if they had received BFT.

The researchers found that BFT increased the amount of new blood vessels in the damaged area of the heart compared with placebo (p<0.01). After the heart attack, levels of the hormones angiotensin II and noradrenaline (which increase blood pressure) were found to increase, but treatment with BFT reduced the levels of both hormones in both the diabetic and non-diabetic mice.

The researchers made a number of discoveries about the actions and mechanisms relating to BFT:

• Treatment with BFT was found to reduce free radical damage of the heart in diabetic and non-diabetic mice.
• The pentose phosphate pathway was more active after heart attack, particularly in the non-diabetic mice.
• BFT increased enzyme activity in the pentose phosphate pathway, including transketolase and an enzyme called G6PD.
• In heart cells, BFT could limit the cell death caused by starving the cell of oxygen. However, when the researchers blocked the activity of the G6PD enzyme BFT was no longer protective to the cells.

How did the researchers interpret the results?

The researchers say that their research shows that the enzymes transketolase and G6PD are less active in the diabetic heart, and that the increased activity of G6PD normally seen in response to a heart attack is blunted in diabetic mice.

The researchers say that “restoring proper G6PD levels may represent a therapeutic target to prevent excessive [heart cell] damage in diabetes”. They say that BFT may improve outcomes after heart attack by promoting G6PD activity, but it may work in other ways too, such as regulating hormone levels, protecting against free radical damage and promoting the formation of new blood vessels.

Conclusion

This basic, preliminary research suggests that mice with chemically-induced type 1 diabetes show poorer recovery from heart attack, but that their recovery can be improved if supplemented with BFT, which promotes the activity of the pentose phosphate pathway.

This study gives useful insights and further research is warranted. As with any animal study, the direct relevance to humans may also be limited.

It is also necessary to consider the high dose of BFT that the mice received (70mg/kg body weight) in order to raise the levels of vitamin B1 in their blood by four-fold. It is not clear what dose humans would need to take to produce a similar elevation, or whether this would be tolerable or safe in humans. Although Marmite may contain vitamin B1 (which is similar to BFT), it is not possible based on this study to say that the amount of vitamin B1 in Marmite has any benefit to diabetics as the Daily Mail has suggested.