Health & Fitness

While many people are now enjoying longer, healthier lives, current retirement ages are posing challenges for both policymakers and retirees. A new study looked into whether there is potential to increase the retirement age based on the relationship between working life expectancy and health aspects important for work ability for women and men in Europe.

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Researchers have found a novel form of the Alzheimer's protein tau in the fluid surrounding the brain and spinal cord. This form of tau -- known as MTBR tau -- indicates what stage of Alzheimer's a person is in and tracks with tangles of tau protein in the brain.

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How well women with cervical cancer respond to treatment and survive correlates with the level of 10 proteins in their blood that also are associated with a 'zombie' cell state called senescence, scientists report.

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A new approach to cancer therapy shows potential to transform the commonly used chemotherapy drug gemcitabine into a drug that kills cancer cells in a specialized way, activating immune cells to fight the cancer.

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Choline is an essential nutrient, but it is not usually classified as a vitamin. According to Biology Online, a vitamin is “a low molecular weight organic compound that is essential for normal growth and metabolic processes and is required in trace amounts.”¹ Since your body can produce some choline in the liver, it is not classified as a vitamin.

Your body needs fat-soluble and water-soluble vitamins to function optimally. Fat-soluble vitamins are stored in fatty tissue and the liver.² They include vitamins A, D, E and K. Water-soluble vitamins are not easily stored and the excess is normally flushed out of your body in the urine. Water-soluble vitamins include vitamin C and all the B vitamins.

Choline is found in fat-soluble and water-soluble compounds in your food.³ Enzymes in your body free the choline from the compounds in your food where it’s absorbed in the small intestines and moved to the liver. Choline is then sent around your body to help make cell membranes.

Your body does not naturally produce enough choline to meet your needs. Therefore, you must get some from the food you eat.⁴ Choline levels are not routinely measured, but most people in the U.S. eat less than the recommended amount of foods containing choline.

While symptoms of a frank deficiency in healthy children and adults are rare, insufficient choline may be linked to health conditions including neurological degeneration and liver disease. Choline functions in the body overlap those of B vitamins, which in part may explain how choline was originally called vitamin B4.

Choline Was Once Considered a Vitamin

The earliest recorded information about choline occurred in 1862 when Adolph Strecker found that when lecithin was heated it generated a new chemical.⁵ He named that chemical choline. Three years later Oscar Liebreich identified a new molecule in the human brain that he named “neurine” and which later turned out to be identical to choline.

Nearly 100 years later in 1954, Eugene Kennedy described a pathway the body uses to incorporate choline into phosphatidylcholine. By this time scientists had identified many of the B complex vitamins.⁶

It wasn't until 1998, though, that the Nutrition Board of the National Academies of Medicine recognized choline as an essential nutrient.⁷ In the fall of 2020, Elena Gagliardi from the ambulatory nutrition services department at Santa Clara Valley Medical Center spoke with a reporter from U.S. News & World Report and explained that choline is not a vitamin.⁸

Instead, it is "a chemical compound vital for its many roles in the body."⁹ Adenine is a chemical constituent of flavin adenine dinucleotide (FAD), which helps convert choline in the mitochondrial matrix.¹⁰

There is a close relationship between adenine and choline — so much so that some also refer to adenine as vitamin B4¹¹ and others use the terms interchangeably.¹² However, it doesn’t matter what term is used, choline is a crucial nutrient for health and wellness.

Choline Is Crucial to Cognitive Function and Liver Health

According to a paper in Nutrition Today, the adequate intake (AI) for choline was calculated when the population levels of it were relatively unknown. Rather than being calculated based on experimental determinations or estimations of intake, it was calculated in part based on a study of adult men who developed liver damage after becoming deficient in it.¹³

The AI levels for others were then extrapolated based on standard reference weights. However, recent analysis has shown nearly 90% of people living in the U.S. do not eat enough choline-rich foods. Added to this, the 2015 to 2020 dietary guidelines for Americans did not recommend sufficient choline-rich foods to meet your needs.

A deficiency in choline can have wide-ranging effects. For example, there are indications that cholinergic dysfunction impacts the development of dementia. Studies and reviews of the literature supported the hypothesis that cholinergic dysfunction contributes to Alzheimer's disease.^14,15

Subsequently, it was discovered acetylcholine plays a central role in the nervous system, which requires an enzyme to synthesize it from acetyl-CoA and choline.¹⁶ The enzyme is called acetyltransferase. This connection likely explains, at least in part, the effect that anticholinergic drugs have on short-term cognitive impairment in the elderly.¹⁷

The medications act on acetylcholine, which sends messages that affect muscle contraction and the part of the brain that handles memory and learning. In one study, 347 participants who had experienced a stroke were given citicoline for 12 months. This is a supplemental combination of choline and cytidine.¹⁸

At the end of 12 months, the researchers found the supplement improved cognitive decline in the participants and “appears to be a promising agent to improve recovery after stroke.” Choline may also be a key factor in nonalcoholic fatty liver disease (NAFLD), which is one of the most common forms of liver disease in the U.S.¹⁹

In part, NAFLD is triggered by obesity and insulin resistance, which scientists find leads to fibrosis and then cirrhosis or liver cancer. There are two forms that are not associated with alcohol consumption. The first is simple fatty liver or nonalcoholic fatty liver (NAFL) and the second is called nonalcoholic steatohepatitis (NASH).

NAFL involves little inflammation or cellular damage, while NASH can lead to fibrosis, cirrhosis or liver cancer. In one study published in the Journal of Nutrition, researchers found women of normal weight who had the highest dietary intake of choline had a lower risk of nonalcoholic fatty liver disease.²⁰

Choline Has a Significant Impact on More Body Systems

According to Chris Masterjohn, Ph.D., choline deficiency may be more significant in the development of NAFLD than consuming too much fructose. His degree is in nutritional science and he believes the rise in fatty liver conditions is largely due to dietary changes.

In his review of the medical literature, Masterjohn found a link between choline and fatty liver, which was initially discovered in research into Type 1 diabetes. He describes the relationship:²¹

"In 1949, however, researchers showed that sucrose and ethanol had equal potential to cause fatty liver and the resulting inflammatory damage, and that increases in dietary protein, extra methionine, and extra choline could all completely protect against this effect.

Conversely, much more recent research has shown that sucrose is a requirement for the development of fatty liver disease in a methionine- and choline-deficient (MCD) model. The MCD model of fatty liver disease is the oldest and most widely used dietary model.

The MCD model produces not only the accumulation of liver fat, but massive inflammation similar to the worst forms of fatty liver disease seen in humans. What no one ever mentions about this diet is that it is primarily composed of sucrose and its fat is composed entirely of corn oil!

The picture that is clearly emerging from all of these studies is that fat, or anything from which fat is made in the liver, such as fructose and ethanol, are required for the development of fatty liver. But in addition to this [same] factor — overwhelmingly, it appears to be choline deficiency — must deprive the liver of its ability to export that fat."

In one study published in the journal Nutrition & Metabolism, researchers enrolled 866 patients with newly diagnosed hepatocellular carcinoma to test survival rates as compared to serum choline levels.²² The data showed patients with higher serum choline levels had better survival rates from liver cancer than those with lower levels.

Choline is a building block of acetylcholine and phosphatidylcholine, a component of very low density lipoproteins.²³ The brain uses phosphatidylcholine to make acetylcholine, which affects cognitive function. Phosphatidylcholine is also used in the treatment of several health conditions, including gallbladder disease, premenstrual syndrome and hepatitis.²⁴

Krill Oil Supports Choline Levels and Physical Performance

Donald Layman, Ph.D., from the department of food science and human nutrition at the University of Illinois, talked about the relationship between exercise performance and choline, saying:²⁵

"Exercise increases energy expenditure, helps maintain body composition, and controls body weight. We all know that routine daily exercise is important, but we often forget that good nutrition choices are essential for optimal muscle performance.

Specifically, choline is part of the neurotransmitter acetylcholine—the signal that stimulates muscle contraction, which supports muscle movement and performance. We also know that choline losses occur after exercise of only an hour, with a long run, cycling or a competitive tennis match."

Choline plays a role in maintaining muscle function. Serum concentrations may be depleted during high-intensity exercise. In one study, researchers engaged 47 triathletes from age 25 to 61 from Ironman distance and Olympic distance triathlons. The group was split into two: 24 received daily krill supplements for five weeks before the race and 23 received a daily placebo of mixed vegetable oils.²⁶

The athletes’ blood was tested before the race, immediately after and the following day. The researchers were analyzing serum choline levels and its metabolites. The data showed serum concentrations decreased significantly in all the races, but those receiving krill oil maintained more of their serum choline than those getting the placebo.

In one lab analysis, researchers found 69 choline-containing phospholipids in krill oil, which confirmed “the complexity of the phospholipid composition of krill oil.”²⁷ The choline composition of krill oil may also be more bioavailable since “It has been suggested that 60% of choline in inorganic salts is lost to conversion to trimethylamine (TMA) by intestinal bacteria.”²⁸

Enzymes may then turn TMA into trimethylamine-N-oxide (TMAO), a potential biomarker for insulin resistance and heart problems. As noted by the researchers, “Choline in the form of PC is considerably less converted to TMA as demonstrated in a single-dose study with krill oil, potentially resulting in more efficient delivery of choline.”²⁹

For example, evidence has shown that 28 days of krill oil supplementation increased choline levels in healthy young adults.³⁰ Additionally, the researchers in this study noted: “no adverse effects on plasma levels of TMAO and carnitine were found.”

How to Get More Choline

In a study comparing phosphatidylcholine, present in krill oil, and choline bitartrate salt, it was found that the krill oil led to higher levels of the important metabolites betaine and dimethylglycine (DMG) along with lower levels of TMAO, which can lead to health issues, compared to the other choline sources.³¹

Krill oil also offers more nutrients, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are beneficial for heart health and have been shown to improve blood pressure,³² reduce overall inflammation, reduce the effects of rheumatoid arthritis³³ and depression³⁴ and help slow the progression of Alzheimer's disease.³⁵

Egg yolks are another excellent choline source. Among egg consumers, approximately 57% met the adequate intake levels for choline, compared to just 2.4% of people who consumed no eggs.³⁶

In fact, the researchers in this same analysis concluded that it’s “extremely difficult” to get enough choline unless you eat eggs or take a dietary supplement, though it’s preferable to get nutrients from dietary sources whenever possible. Other dietary sources of choline include:^37,38

Grass fed beef liver	Organic pasture raised chicken	Wild-caught Alaskan salmon
Roe fish eggs	Atlantic cod	Kidney beans
Quinoa	Brussels sprouts	Broccoli
Shiitake mushroom	Cauliflower	Sunflower seeds

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There’s good news for those of you who have taken the proactive step to make sure your vitamin D level is optimized. Several recent studies demonstrate vitamin D can have a significantly beneficial impact on your cancer risk, both in terms of preventing cancer and in the treatment of cancer.

Vitamin D Reduces Cancer Mortality

In the first of these studies,^1,2 which included 25,871 patients, vitamin D supplementation was found to reduce the risk for metastatic cancer and death by 17%. The risk was reduced by as much as 38% among those who also maintained a healthy weight.

This was a really poorly done study as they only gave participants 2,000 IUs a day and never measured their blood levels. Had there been no improvement, I would not have been surprised, but the fact is it still reduced metastatic cancer and death by 17%, and they found significant benefit among those who were not obese.

This is pretty extraordinary but not as good as epidemiological studies that show a 50% to even 78% reduction in vitamin D sufficient people, as suggested in a study further below. That said, UPI reported the results saying:³

“The benefits of vitamin D3 in limiting metastases — or disease spread to other organs — and severity was seen across all cancers, and was particularly prominent among study participants who maintained a healthy weight …

‘The primary message [of our study] is that vitamin D may reduce the chance of developing metastatic or fatal cancer among adults without a diagnosis of cancer,’ study co-author Dr. Paulette Chandler told UPI.”

The study, published in JAMA Network Open, is a secondary analysis of the VITAL Study⁴ which, in part, sought to determine whether taking 2,000 IUs of vitamin D per day would reduce the risk of cancer, heart disease or stroke in people who did not have a prior history of these diseases.

The VITAL study itself, which followed patients for an average of 5.3 years, found no statistical difference in overall cancer rates among those who took vitamin D3, but there was a reduction in cancer-related deaths, which is what prompted this secondary analysis.

Obesity May Inhibit Vitamin D’s Benefits

The fact that patients with a healthy weight derived a much greater benefit — a 38% reduced risk for metastatic cancer and death compared to 17% overall — suggests your body weight may play a significant role in whether vitamin D supplementation will provide you with the anticancer benefits you seek.

According to study co-author Dr. Paulette Chandler, assistant professor of medicine at Brigham and Women's Hospital in Boston, “Our study highlights that obesity may confer resistance to vitamin D effects.”⁵

There may be something to that. Research⁶ published in 2010 found that dietary fructose inhibits intestinal calcium absorption, thereby inducing vitamin D insufficiency in people with chronic kidney disease.

That said, vitamin D tends to be lower in obese people in general, for the fact that it’s a fat-soluble nutrient and when you’re obese, the vitamin D ends up being “volumetrically diluted.” As explained in the paper “Vitamin D in Obesity,” published in 2017:⁷

“Serum vitamin D is lower in obese people; it is important to understand the mechanism of this effect and whether it indicates clinically significant deficiency … Vitamin D is fat soluble, and distributed into fat, muscle, liver, and serum.

All of these compartments are increased in volume in obesity, so the lower vitamin D likely reflects a volumetric dilution effect and whole body stores of vitamin D may be adequate … Obese people need higher loading doses of vitamin D to achieve the same serum 25-hydroxyvitamin D as normal weight.”

While that particular paper stresses that lower vitamin D in obese individuals might not mean that they’re deficient, others disagree. For example, one study^8,9 found that for every 10% increase in body-mass index, there’s a 4.2% reduction in blood levels of vitamin D. According to the authors of that particular study, obesity may in fact be a causal factor in the development of vitamin D deficiency.¹⁰

Vitamin D Also Improves Colorectal Cancer Outcomes

A scientific review¹¹ published in the September 2020 issue of the British Journal of Cancer noted that having low vitamin D is associated with poor colorectal cancer survival.

To assess whether vitamin D supplementation might improve survival in these patients, they reviewed the findings of seven trials, three of which included patients diagnosed with colorectal cancer from the outset and four population trials that reported survival in incident cases.

Overall, the meta-analysis found supplementation resulted in a 30% reduction in adverse colorectal cancer outcomes. Vitamin D also improved outcomes among patients already diagnosed with colorectal cancer. According to the authors:¹²

“Meta-analysis demonstrates a clinically meaningful benefit of vitamin D supplementation on [colorectal cancer] survival outcomes. Further well-designed, adequately powered RCTs are needed to … [determine] optimal dosing.”

Low Vitamin D Linked to Increased Cancer Incidence

Another review and meta-analysis,¹³ this one published in November 2019 in Bioscience Reports, looked at vitamin D supplementation on cancer incidence and mortality in general. Ten randomized controlled trials with a pool of 81,362 participants were included in the analysis.

While the incidence rate of cancer was very similar between the vitamin D intervention group and the placebo control group (9.16% versus 9.29%), the risk reduction in mortality was deemed “significant.” As reported by the authors:

“The mortality rate of cancer was 2.11% (821 cases) and 2.43% (942 cases) in vitamin D intervention group and placebo group, respectively, resulting in a significant reduction in risk (RR = 0.87).

There was no observable heterogeneity or publication bias … Our findings support a beneficial effect of vitamin D supplement on lowering cancer mortality, especially in subpopulations with no history of cancer, extra use of vitamin D, or calcium supplement.”

Vitamin D Protects Against Breast Cancer

Several studies have highlighted the benefit of vitamin D for breast cancer. For example, an analysis¹⁴ by GrassrootsHealth published June 2018 in PLOS ONE showed women with a vitamin D level at or above 60 ng/mL (150 nmol/L) had an 82% lower risk of breast cancer compared to those with levels below 20 ng/mL (50 nmol/L).

An earlier study,^15,16 which looked at women in the U.K., found having a vitamin D level above 60 ng/mL resulted in an 83% lower breast cancer risk, which is nearly identical to GrassrootsHealth’s 2018 analysis.

One of the most recent meta-analyses^17,18 looking at breast cancer was published December 28, 2019, in the journal Aging. Here, they reviewed 70 observational studies, finding that for each 2 ng/mL (5 nmol/L) increase in vitamin D level there was a corresponding 6% decrease in breast cancer incidence.

Overall, this translates into a 71% reduced risk when you increase your vitamin D level from 20 ng/mL to 60 ng/mL. The following graph, created by GrassrootsHealth,¹⁹ illustrates the dose response between vitamin D levels and breast cancer risk found in this study.

GrassrootsHealth’s 2018 analysis in PLOS ONE also analyzed this dose relationship.²⁰ To do that, they looked at the percentage of breast cancer-free participants in various vitamin D groups, from deficient (below 20 ng/mL) to optimal (at or above 60 ng/mL), over time (four years).

As you might expect, the higher the blood level of vitamin D, the lower the incidence of breast cancer. The graph below illustrates this dose-related protection. At four years, the percentage of women who had been diagnosed with breast cancer in the 60 ng/mL group was 78% lower than among those with blood levels below 20 ng/mL.

How to Optimize Your Vitamin D Level

If you live in the northern hemisphere, which is currently heading toward winter, now is the time to check your vitamin D level and start taking action to raise it if you’re below 40 ng/mL (100 nmol/L). As you can see from the studies above, a vitamin D level of 60 ng/mL (150 nmol/L) or higher is recommended if you want to protect against cancer.

An easy and cost-effective way of measuring your vitamin D level is to order GrassrootsHealth’s vitamin D testing kit. Once you know your current vitamin D level, use the GrassrootsHealth vitamin D calculator²¹ to determine how much vitamin D you might need to reach your target level. To optimize vitamin D absorption and utilization, be sure to take your vitamin D with vitamin K2 and magnesium.

Lastly, remember to retest in three to four months to make sure you’ve reached your target level. If you have, then you know you’re taking the correct dosage. If you’re still low (or have reached a level above 80 ng/mL), you’ll need to adjust your dosage accordingly and retest again in another three to four months.

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