Category: 8. Health

Three people in China had to be hospitalised after they ate sheep placenta for “nutritious” purposes, sparking an online discussion about the custom.

A woman, surnamed Zhang, in southern China’s Guangdong province was reported to have developed frequent fevers and lost 5kg in weight over a short period after she cooked the “dish”.

She went to hospital and was diagnosed with brucellosis, a type of bacterial infection spread from animals to humans.

Zhang’s sister and brother-in-law were diagnosed with the same disease after eating the “tonic”.

The placenta is an organ that forms in the uterus during pregnancy and is considered a highly nutritious ingredient in China.

In Traditional Chinese Medicine, the placenta is known as ziheche.

It is believed to strengthen the immune system, treat fatigue, infertility and a lack of energy.

Eight essential nutrients make up the suite of B vitamins also known as the B complex. Researchers from Tufts University and elsewhere have revealed that these B vitamins influence a vast spectrum of human health and disease, including cognitive function, cardiovascular health, gastric bypass recovery, neural tube defects, and even cancer.

“It’s hard to study the B vitamins in isolation,” says gastroenterologist Joel Mason, senior scientist at the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) and professor at the Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy and Tufts University School of Medicine. “Four of these B-vitamins cooperate as co-factors in many critical activities in cells in what we call ‘one carbon metabolism’.”

One carbon metabolism is a series of pathways that allow for the transfer of single-carbon units to cells for essential processes such as DNA synthesis, amino acid metabolism, and more. It’s their role in all these crucial biological functions that make the B vitamins so important-and so challenging to tease out how they contribute positively and, perhaps negatively, to human health.

Mason and two additional researchers who spent their careers studying one or more of the B vitamins explain what we currently know about how the five of the most prominently researched B vitamins impact or improve cognitive as well as cardiovascular health.

Cognitive Health, B₁₂, and Folate

One of the most active areas for B vitamin research is cognitive health. By the age of 75-80, 40% of people have a diminished ability to absorb food-bound B₁₂, says Mason. This deficiency leads to a decline in nerve health, particularly in the spine and brain, which can contribute to the risk of developing dementia in older adults. 

For decades, clinicians and researchers thought measuring plasma B₁₂ was accurate enough to determine if supplementation was needed. However, Mason says, while many elderly people may have B₁₂ levels that are in the ‘low to normal’ range, they are simultaneously developing neurological deficits linked to vitamin B₁₂ deficiency. 

The contribution of vitamin B₁₂ deficiency to cognitive decline and the vascular disease that results in many cases of dementia is under-diagnosed and under-reported.”

Irwin H. Rosenberg, Jean Mayer University Professor Emeritus, Tufts University

Rosenberg is also a former dean of the Friedman School of Nutrition Science and Policy who also taught pharmacology at the School of Medicine. 

“Age-related cognitive decline is not just Alzheimer’s,” says Rosenberg. “We’ve lumped together many kinds of brain dysfunction under one name. And in doing so, we’ve overlooked how critical blood vessels-and by extension, nutrition-are to preserving brain function.”

The pathology of Alzheimer’s disease described the abnormal buildup of two proteins in the brain-amyloid and tau-which clump together, forming plaques and tangles which are believed to disrupt brain cell function. 

Yet Rosenberg says cerebrovascular disease and small vessel disease, which in some cases are connected to B vitamin deficiency, is more prevalent with cognitive decline and dementia than the buildup of harmful proteins in the brain, which has been the focus of so much research and drug development to treat Alzheimer’s disease. Treating people with drugs meant to address the protein buildup will not work if the cause of dementia symptoms is a B₁₂ deficiency.

Testing to identify whether cognitive decline and dementia symptoms may be caused by a B₁₂ deficiency is therefore imperative, he says.

“B₁₂ tests measure all B₁₂ in your system, even though approximately 80% is inactive,” says Paul Jacques, senior scientist at the HNRCA and professor at the Friedman School of Nutrition Science and Policy.

To pinpoint a B₁₂ deficiency requires two additional tests. One, called the MMA test, measures levels of methymalonic acid, an acid produced during certain aspects of metabolism requiring adequate B₁₂. “It can be elevated with even a mild B₁₂ deficiency, indicating a potential higher risk of dementia,” says Jacques.

A second test measures levels of an amino acid, homocysteine, which is also a byproduct of metabolism requiring B₁₂. If only homocysteine levels are elevated, a folate deficiency may be the problem. If both MMA and homocysteine are high, a B₁₂ deficiency is the likely culprit.

If a patient presents with neurological issues or signs of dementia, conducting all three tests will narrow down if a B vitamin deficiency is involved-and which B vitamin it is.

“Unlike changes that we are unable to see in patients being given expensive anti-amyloid antibody drugs to treat Alzheimer’s disease, there is actually evidence that fairly early in the course of cognitive decline we can slow the process if the underlying cause is elevated homocysteine or B₁₂-related deficiency,” says Rosenberg. “It’s my recommendation that patients, with or without anemia, should be screened for elevated homocysteine or B₁₂ deficiency because that may be one of the reversible factors in their cognitive decline.”

This isn’t a new theory. Two decades ago, studies like the Framingham Heart Study showed that elevated homocysteine predicted brain atrophy and a higher risk of dementia. More recently, trials such as VITACOG and FACT have shown that B vitamin supplementation can slow brain shrinkage and improve cognitive performance in those at risk.

“There is an enormous amount of education needed around this issue,” Rosenberg says. “We hope to convince cardiologists, neurologists, and internists to measure B₁₂ and homocysteine levels as part of the evaluation of cognitive impairment. Even the modest effects from vitamins that cost pennies a day can be very meaningful in those who will benefit, especially when you compare vitamin supplementation to costly drugs that are getting much more attention yet may have the same or even less benefit.”

B₁₂ and Dementia

Jacques and colleagues currently are leading a study using data from about 2,500 middle-aged and older adults in the Framingham Heart Study, all of whom were free of dementia in the 1990s and all of whom received B₁₂, MMA, and homocysteine testing for the last 20+ years.

“The risk of dementia and late-stage Alzheimer’s begins to increase when one is 75 years old or older, but evidence suggests that some of the pathological changes associated with dementia and Alzheimer’s may start to develop 20+ years before clinical symptoms and diagnosis occurs,” says Jacques. “This study should give us a good handle on whether B₁₂ is related to cognitive decline and dementia. If so, hopefully we can identify a simple, inexpensive intervention that could be started years in advance and before real damage occurs.”

Jacques is also looking at the role folate (B₉) may play in the development of cognitive issues, specifically the influence high levels of folate might have on B₁₂ and cognitive health.

In the 1950s, people with anemia were treated with folic acid, the synthetic form of folate. Unfortunately, it became clear that while pharmaceutical level treatment with folic acid alleviated anemia, it often masked or exacerbated B₁₂ deficiency. “Scientists observed that people with low B₁₂ and high folic acid concentrations tended to have cognitive issues,” Jacques says.

More recent research suggested that it wasn’t total B₁₂ concentrations that folic acid might be affecting, but perhaps just one component, holoTC, which is the form of vitamin B₁₂ that is crucial for transporting and using B₁₂ in cells and is considered a potentially better indicator of vitamin B₁₂ status. 

Jacques and colleagues are conducting two studies to tease apart the issues involved. “In the first, our B vitamin and brain aging study, we will look at the influence high folate status has on the relationships between B₁₂ and cognitive health. A second study we are doing in collaboration with Rutgers will look at the effect of high folic acid in the blood on the two forms of B₁₂ -holoTC and unbound cobalamin.”

Heart disease, cholesterol, and stroke

B vitamins have also stirred excitement among researchers because of their possible role in heart disease and stroke prevention, but thus far their utility as a clinical treatment remains limited.

Scientists discovered in the early 2000s that riboflavin (B₂) could decrease blood pressure very effectively. It is believed that riboflavin improves a biochemical reaction mediated by a gene called MTHFR (methylenetetrahydrofolate reductase) that helps the body use folate. Riboflavin is only effective in reducing blood pressure specifically in patients with the MTHFR 677 TT genotype, however.

Vitamins B₆, B₁₂, and folate help the body rid itself of homocysteine, which in overabundance had been linked to an increased risk of heart attacks and strokes, as well as dementia. However, a number of clinical trials in the 1980s showed that B₆, B₁₂, and folate supplementation didn’t decrease heart attacks, but did slightly lower the risk of strokes.

Niacin (B₃) can lower LDL (the so-called “bad cholesterol”) and raise HDL (the so-called “good cholesterol”). “But it has to be taken in such large doses that it often causes very uncomfortable flushing, like hot flashes,” says Mason. “People often can’t tolerate taking it, and other drug options are available that lower blood LDL that do not have such unpleasant side effects.”

Chronic inflammation and B₆

Perhaps most promising for the future is the role vitamin B₆ may play in curbing inflammation, which has been identified as an underlying feature of many chronic diseases, from heart disease to diabetes to arthritis to dementia.

A number of animal studies, plus some human studies, suggest that supplemental B₆ can reduce inflammation. “Again, we are talking about giving B vitamins at an appropriate pharmaceutical level under the care of a clinician,” cautions Mason. “B₆ can be toxic in large amounts.” He sees this research as an area to watch in the years ahead.

Researchers at Johns Hopkins Medicine say they unexpectedly found new information about a protein’s special role in getting brain cells to communicate at the right time and place in experiments with genetically engineered mice.

The finding about the protein intersectin, they say, advances scientific understanding of a key process in how the mammalian brain forms memories and learns, and may help advance treatments for cognitive disorders including Down syndrome, Alzheimer’s disease and Huntington’s disease.

A report of the new findings, funded in part by the National Institutes of Health, was published July 8 in the journal Nature Neuroscience. 

Specifically, the researchers found that intersectin keeps tiny, message-carrying bubbles inside brain cells in a particular location until they are ready to be released to activate a neighboring brain cell. The protein does so by creating a physical boundary between these bubbles, similar to how oil separates from water.

Message transfer from brain cell to brain cell is key to information processing, learning and forming memories. The bubbles, synaptic vesicles, are housed within the synapse – the connection point where brain cells communicate.

In typical synapses within the brains of mammals, 300 synaptic vesicles are clustered together in the intersection between any two brain cells, but only a few of these vesicles are used for such message transfer, researchers say. Pinpointing how a synapse knows which vesicles to use has long been a target of research by those who study the biology and chemistry of thought.

We found that these tiny bubbles have a distinct domain where they want to be. Keeping them at particular locations within a synapse enables the brain to decide how and when to use them while thinking and processing information.”

Shigeki Watanabe, PhD, Study Lead and Associate Professor, Cell Biology, Johns Hopkins Medicine

In an effort to better understand the operation of these synaptic vesicles, Watanabe and his team designed a study that first focused on endocytosis, a process in which brain cells recycle synaptic vesicles after they are used for neuronal communication.

Already aware of intersectin’s general role in endocytosis and neuronal communication, the scientists genetically engineered mice to lack the gene that codes for intersectin. However, and somewhat to their surprise, Watanabe says removing the protein did not appear to halt endocytosis in brain cells.

The research team refocused their experiments, taking a closer look at the synaptic vesicles themselves.

Using a high-resolution fluorescence microscope to observe where intersectin is in a synapse, the researchers found it in between vesicles that are used for neuronal communication and those that are not, as if they are physically separating the two.

To further understand the role of intersectin at this location, they used an electron microscope to visualize synaptic vesicles in action across one billionth of a meter. In all the nerve cells from mice lacking this protein, the scientists say synaptic vesicles close to the membrane were absent from the release zone of the synapse, the place where the bubbles would discharge to nearby neurons.

“This suggested that intersectin regulates release, rather than recycling, of these vesicles at this location of the synapse,” says Watanabe.

Using a technique called zap and freeze microscopy, the scientists stimulated neurons in the brains of mice to capture the movement of synaptic vesicles on a millisecond timescale and at a nanometer resolution.

In normal mice, the scientists saw vesicles fusing with the brain cell membrane within a millisecond after stimulation. Then, new synaptic vesicles came and filled the vacated release sites of the synapse within about 15 milliseconds.

In two genetically engineered lines of mice, one lacking intersectin and another lacking the endophilin protein, which binds to intersectin, new vesicles could not be recruited to the vacated release sites. Similarly, vesicles within nerve cells of mice with mutations that blocked the interaction of these two proteins also slowed the local replenishment of synaptic vesicles that carry information from neuron to neuron.

“When information is processed in the brain, this replenishment process needs to happen in just a few milliseconds,” says Watanabe. “When you don’t have vesicles staged and ready to go at the release sites or the active zones, then neurotransmission cannot continue.”

In future research, the scientists say they aim to better understand how intersectin shuttles new synaptic vesicles to release sites.