Marc Joseph Nutrition - Blog

In a recent epidemiological study of rural Chinese seniors, researchers found that lower selenium levels in nail samples were associated with lower cognitive scores.

Specifically, researchers observed that people in the group with the 20% lowest selenium levels scored 10 years older on a standardized cognitive test than people with the 20% highest selenium levels.

Selenium is an essential trace mineral — meaning you only need very small amounts of it (micrograms - mcgs, or millionths of a gram) and have to get it from your diet or through supplements. Selenium may also be toxic in higher amounts (e.g., more than 400 mcg/day), so this is a case where a lot more is not better.

The mineral plays very important roles in the body, such as inclusion in key enzymes:

• Glutathione peroxidases, which help one of the body’s primary antioxidants (glutathione) to neutralize free radical molecules.
• Thyroid hormone deiodinases, which help convert inactive thyroid hormone T4 into the biologically active form T3, among other functions.

Selenium may help to reduce the risk of certain cancers (e.g., prostate, colon), improve immune function, and lower the risk of cardiovascular disease (via reduced oxidative damage to the arterial walls). Also, selenium appears to sequester, although not chelate, mercury.

Brazil nuts are the food highest in selenium (potentially > 100 mcg per nut, depending on the soil). Organ meats and seafood are also high in selenium. Selenium levels in grains and plant foods can vary greatly depending on the soil in which they are grown. Here’s an (old) map that shows soil selenium levels in North America.

As the authors of the study above note, it’s important to realize that the effects of selenium deficiency likely occur over a long period. Selenium supplementation is not a quick fix. Including a reasonable amount of selenium (e.g, 200 mcg/day) in a well-utilized form (e.g., selenomethionine) as part of a preventive program started well before cognitive decline symptoms appear makes the most sense.

In a recent study published in the American Journal of Clinical Nutrition, researchers found that higher levels of vitamin A intake were associated with lower rates of gastric cancer.

Specifically, researchers, in an observational cohort study, looked at vitamin A consumption through both food and supplements, and noted that:

[H]igh intakes of vitamin A and retinol from foods only (dietary intake) and from foods and supplements combined (total intake) and of dietary alpha-carotene and beta-carotene were associated with a lower risk of gastric cancer.

The reduction in gastric cancer risk ranged from 45 to 50 percent.

Vitamin A - Forms & Functions

There are three biologically active forms of vitamin A:

• retinal
• retinol
• retinoic acid

Retinal is primarily derived from beta-carotene, one of the plant pigments (carotenoids) found in foods such as carrots, spinach, yams, etc. It can be converted in the body into retinol in a reversible reaction and into retinoic acid in an irreversible reaction. Retinal plays an important role in vision.

Retinol is found only in animal products, such as liver, cod liver oil, and milk. It can also be created through conversion from retinal in a reversible reaction. Retinol plays important roles in reproduction and growth.

Retinoic acid is derived from retinal in an irreversible reaction and plays important roles in gene expression and growth.

Suspected Vitamin A Role in Gastric Cancer

Vitamin A (primarily retinoic acid and retinol) is key in controlling cell differentiation and proliferation, two activities that go awry in cancer. Vitamin A helps to:

• control protein synthesis and differentiation of epithelial cells that line the body’s surfaces, such as the skin and the linings of the mouth, stomach, and intestines.
• regulate differentiation of goblet cells that produce mucus that coats and protects the epithelial cells from both bacteria and potentially harmful substances, such as gastric juices.

Vitamin A also influences immune system function, and helps to ensure proper T-cell response and natural killer cell activity, both critical in helping to prevent cancer from developing.

Clearly, it’s important to ensure adequate intake of all vitamin A forms, from both food and potentially supplements, to help reduce gastric cancer risk.

Even more research evidence just out reinforcing the importance of adequate vitamin D levels for avoiding the development of breast and colon cancers.

In the first paper published in the Journal of Steroid Biochemistry and Molecular Biology, researchers pooled data from two previous studies and found that individuals with the highest vitamin D levels (greater than 50 ng/mL) had one-half the risk of developing breast cancer versus individuals with the lowest vitamin D levels (less than 10 ng/mL).

“The data were very clear, showing that individuals in the group with the lowest blood levels had the highest rates of breast cancer, and the breast cancer rates dropped as the blood levels of 25-hydroxyvitamin D increased,” said study co-author Cedric Garland, Dr.P.H. “The serum level associated with a 50 percent reduction in risk could be maintained by taking 2,000 international units of vitamin D3 daily plus, when the weather permits, spending 10 to 15 minutes a day in the sun.”

In the second paper published in the American Journal of Preventive Medicine, researchers found that individuals with the highest vitamin D levels had the lowest colon cancer risk.

“Through this meta-analysis we found that raising the serum level of 25-hydroxyvitamin D to 34 ng/ml would reduce the incidence rates of colorectal cancer by half,” said co-author Edward D. Gorham, Ph.D. “We project a two-thirds reduction in incidence with serum levels of 46ng/ml, which corresponds to a daily intake of 2,000 IU of vitamin D3. This would be best achieved with a combination of diet, supplements and 10 to 15 minutes per day in the sun.”

Sources

The primary source of vitamin D is sunshine (UVB rays) hitting the skin, converting cholesterol-based molecules there into a molecule called cholecalciferol, which is then converted by two more reactions in the liver and kidneys into the final, active form of vitamin D (calcitriol).

Interestingly, researchers have learned in recent years that the final conversion that takes place in the kidneys can also take place in other cells in the body, such as breast, colon, prostate, and skin cells, four cell types that are prone to cancer.

Food is a poor source of vitamin D. Only fortified dairy really contains significant amounts, and then, only about 100 IU in an 8 oz. glass of milk. Not much.

If you get vitamin D through sun exposure, you want to avoid getting too much exposure and damaging the skin. You don’t want the skin to change color. 10 to 15 minutes per day of noontime sun on a clear day three or four times a week for a fair-skinned person should be fine. Dark-skinned people need significantly more exposure, e.g., 25 to 30 minutes exposure each time out.

In Northern latitudes during the winter months, the sun isn’t strong enough to generate adequate vitamin D, even during mid-day sun. Supplementation is the preferred source.

Getting 2000 IU/day of vitamin D through supplementation is both easy and inexpensive (less than $15 a year). As long as people aren’t getting regular, significant sun, such an intake level year-round is likely to be safe and promote healthful vitamin D levels that may:

• reduce the risk for several types of cancer
• improve calcium utilization and bone density
• strengthen immunity and reduce susceptibility to the flu

As the evidence continues to mount, last month’s appeal by leading researchers for an increase in the vitamin D upper intake level, as well as higher daily recommended intake levels for optimal health, needs to be taken seriously.

A new study just out in Cancer Research journal found that tomato and broccoli consumption (10% of the diet) helped to significantly reduce prostate cancer tumor size in rats (34% and 42%, respectively). Interestingly, reduction in tumor size was even greater (52%) in rats consuming both tomatoes and broccoli.

On the other hand, rats given supplements of lycopene, a carotenoid found in tomatoes and associated with the prevention of prostate cancer, only saw reductions in tumor growth of 7 to 18 percent, depending on the dose. Not bad, but the foods themselves proved superior.

Broccoli and other vegetables, such as cabbage and cauliflower, are high in glucosinolates (e.g., sulforaphane, indole-3-carbinol) that are also associated with cancer prevention.

A few comments:

1. This study was an animal study and the results may not directly correspond to results in humans. However, as discussed in the links above, there is significant evidence that phytochemicals found in vegetables such as tomatoes and broccoli may have anti-cancer effects.

2. The study authors note that you’d likely have to eat a fairly large amount of tomatoes or broccoli daily to get the effects in this study (1.4 cups of raw broccoli and 2.5 cups of fresh tomato, or 1 cup of tomato sauce, or half a cup of tomato paste). That’s quite a bit (watch the salt on that tomato paste), but it’s doable.

3. I wouldn’t eat broccoli every day. As part of the cabbage family, it’s a goitrogen, and may inhibit thyroid function if eaten too frequently in large quantities. A few times a week should be no problem.

4. Lycopene seems to be better absorbed through food than supplements.

5. Lycopene and other carotenoids are best absorbed with meals
containing fat (e.g., olive oil).

6. An easy, inexpensive way to incorporate tomatoes into your diet on a regular basis is to use Low-Sodium V8 juice. It has only 140 mg sodium and 17 mg lycopene per 8 oz. serving. Of course, it would be best to drink it with a meal containing fat or mix a little added healthy fat (e.g., olive oil) in with it to promote best absorption of the lycopene and other beneficial phytochemicals.

In short, regular consumption of tomatoes and/or broccoli (don’t always have to be together) can be a good part of a cancer prevention/treatment diet.

You can read more about things you can do to help maintain a healthy prostate here.

Leading scientists affiliated with the Council for Responsible Nutrition, Mount Sinai Hospital (Toronto), and Creighton University published a review article in the most recent issue of the American Journal of Clinical Nutrition calling for a five-fold increase in the recommended tolerable upper intake level (UL) of vitamin D.

(UL = the maximum level of daily nutrient intake that is likely to pose no risk of adverse effects)

The current vitamin D UL is 2000 IU (50 micrograms/day). The article’s authors review the existing research and make the case that the UL should be raised to 10,000 IU (250 mcg/day).

The UL established by the FNB [Food & Nutrition Board] for vitamin D (50 mcg, or 2000 IU) is not based on current evidence and is viewed by many as being too restrictive, thus curtailing research, commercial development, and optimization of nutritional policy. Human clinical trial data published subsequent to the establishment of the FNB vitamin D UL published in 1997 support a significantly higher UL.

The authors note that the initial UL was set based primarily on research associated with the function of vitamin D in bone formation, but that more recent research has shown vitamin D to play important roles in other areas (e.g., immunity), and that potentially higher necessary levels may be necessary for optimal function. The authors cite several clinical trials using as much as 1250 mcg/day of vitamin D with no observed negative side effects.

The primary source of vitamin D is sunshine, with the average diet providing less than 10 mcg (or 400 IU/day) — and that’s only in people regularly consuming significant amounts of vitamin D fortified foods, such as some dairy products.

As discussed frequently in this blog, vitamin D deficiency is widespread, with some estimates suggesting as much as 60 percent of people in Northern latitudes aren’t getting enough. Deficiency rates are also high among certain groups at all latitudes, such as among the elderly and people who work inside all day.

See this recent post for more vitamin D discussion and embedded links to several other posts relevant to the topic:

Higher Vitamin D Levels May Help Protect Against Multiple Sclerosis

Hopefully the Food and Nutrition Board, which is responsible for setting recommended intake and ULs, will seriously consider this call for an increase in vitamin D levels.

Vitamin B12 is a critical nutrient in helping to maintain cognitive function, as one of its primary roles is to aid in the formation of myelin, the insulation that lines nerve cells, such as brain cells. It’s also a key nutrient in a process called methylation, which helps control the expression of genes and proteins that are involved in many important chemical pathways in the body. An imbalance in methylation may also play a role in cancer development.

Deficiency of vitamin B12 is most commonly observed in older adults, partly because of dietary changes (less meat intake), but also as the result of impaired absorption. When foods containing vitamin B12 (e.g., meat) are eaten, intrinsic factor, a substance secreted by cells in the stomach, binds to vitamin B12. That compound travels to the end of the small intestine, where it separates and vitamin B12 is absorbed. If for some reason the stomach or gastrointestinal tract is damaged (e.g., as in atrophic gastritis) or stomach acid production is slowed (e.g., with medications such as proton pump inhibitors), this multi-step absorption process may be interrupted.

Once vitamin B12 is absorbed, utilization in the body and methylation pathways may also be impaired by the presence of heavy metals, such as mercury, lead, and aluminum.

Several laboratory measures are used together (by thorough practitioners) to test for vitamin B12 deficiency, including:

• Serum vitamin B12
• Methylmalonic acid (MMA)
• Homocysteine

In a recent paper published in the American Journal of Clinical Nutrition, researchers found that high MMA values (suggestive of vitamin B12 deficiency) were associated with significantly lower scores on a standard cognitive assessment tool, especially in the areas of language comprehension and expression.

Low serum folic acid levels also were associated with poorer cognitive function scores. Folic acid, along with vitamin B12, is essential in the proper functioning of methylation pathways, which often are not working correctly in conditions such as cognitive decline, autism, and ADD/ADHD.

Lest you think that these deficiencies only affect a small percentage of people, 43 percent of the non-demented individuals age 69 and older in the study had MMA values that suggested significant vitamin B12 deficiency.

It’s critically important to make sure that both vitamin B12 and folate levels are maintained at adequate levels to reduce the risk of cognitive decline. You can learn more about treatment approaches for preventing and slowing cognitive decline here.

With many baby boomers about to retire, maintaining independence and the ability to live an active, engaged retirement are top of mind. A recent study published in the Archives of Internal Medicine found that deficiencies in several micronutrients may increase the risk for having difficulty performing daily tasks as people age.

Specifically, the study looked at women over the age of 65 and found that deficiencies in selenium, vitamin B6, and vitamin B12 were all associated with significantly greater risk of experiencing disability, which was defined as self-reported difficulty in performing two or more activities such as bathing, dressing, toileting, transferring and eating.

Selenium is an essential trace mineral that is used by the body in important antioxidant-related enzymes. Selenium also plays an important role in immune function and may help to prevent the onset of certain cancers, such as prostate cancer.

Vitamin B6 and B12 are involved in important enzyme reactions, nervous system function, and help to maintain low homocysteine levels. High homocysteine levels are associated with oxidative stress, endothelial dysfunction, vascular diseases (heart disease, stroke), and, in particular, with decline of cognitive function.

Nutritionally, your best bet for avoiding the potential problems highlighted by this study are to follow a good diet, including mostly whole foods, lots of fresh vegetables & fruits, healthy fats, and lean protein sources.

Also, supplementation with a broad-based multi-vitamin/mineral containing at least 200 mcg selenium and the B vitamin equivalent of a B-50 complex, may help to ensure that you get adequate amounts of these essential nutrients on a regular basis and to prevent/delay the onset of disability. It’s important to select supplements containing both adequate and well-absorbed forms of the different nutrients.

In a study recently published in the Journal of the American Medical Association, researchers found that Caucasians with the highest vitamin D levels (25-hydroxyvitamin D > 99.1 nmol/L) had a 62% lower risk of developing multiple sclerosis (MS) than those people with the lowest vitamin D levels (< 66.3 nmol/L). The inverse relationship between MS and vitamin D level was especially strong for people younger than 20 years.

This study adds to a fairly substantial body of earlier research that suggests vitamin D may play an important role in MS. Here’s a good overview article on the topic, as well as a map showing how MS cases seem to vary by latitude.

I’ve posted several times in the past about the importance of vitamin D in helping to prevent the development of various conditions:

• Epidemic Influenza and Vitamin D
• Vitamin D Deficiency Increases Risk of Nursing Home Admission
• Vitamin D Could Reduce Pancreatic Cancer Risk
• Vitamin D Deficiency During Pregnancy

Making sure that your vitamin D levels (25-hydroxyvitamin D) are at least in the high end of the normal range (45-50 ng/mL or 112-125 nmol/L) year-round is a smart step for ensuring better health.

New study (full text) out in the journal Archives of Internal Medicine that found that long-term supplementation of vitamin E in generally healthy older women did not significantly reduce the risk of cognitive decline.

But there may be more to the story.

Vitamin E is a powerful, fat-soluble antioxidant that helps to protect fatty substances in the body, such as cell membranes, nerve cells, lipoproteins, etc. Since oxidative stress is commonly observed in neurodegenerative diseases (e.g., Alzheimer’s) at even the earliest stages of the disease process, the thinking is that antioxidants such as vitamin E may help to reduce the onset and/or progression of the conditions.

There are actually eight forms of vitamin E: 4 tocopherols (alpha, beta, delta, gamma) and 4 tocotrienols (alpha, beta, delta, gamma). This study only used the alpha-tocopherol form of vitamin E. In earlier studies looking at vitamin E and cognitive decline, discussion regarding the type of vitamin E used has rarely been included. However, the authors of this study did raise this point (as did an editorial that accompanied the article):

It has been suggested that tocopherols such as {gamma}-tocopherol that is found in foods rather than in supplements* may be more important for delaying brain aging. Although {alpha}-tocopherol has stronger antioxidant properties, {gamma}-tocopherol has important additional anti-inflammatory effects that may enhance neuroprotection.

(* Broad-based vitamin E supplements containing gamma-tocopherol definitely are widely available. Well, at least the authors mentioned the issue.)

Also, recent research suggests that high amounts of alpha-tocopherol
may actually deplete gamma-tocopherol levels in the body. Given this potential, as well as gamma-tocopherol’s unique anti-inflammatory and antioxidant properties (e.g., its ability to inhibit cyclooxygenase and neutralize reactive nitrogen species — the latter especially relevant in protecting nervous system cells), it seems to make more sense to study the effects of a more balanced form of vitamin E on cognitive decline.

Other potential reasons why a beneficial result may have not been observed in this study:

• The dose given (600 IU, every other day) may have been too low.
• The supplements may not have been regularly taken with meals containing fat. Vitamin E is a fat-soluble vitamin and is not well absorbed unless taken with adequate amounts of fat.
• The timing of the initiation and length of the study may have been sub-optimal. Participants in this study were enrolled in their 60’s and given supplements for 10 years. Better results may have been observed if supplementation was started earlier in life and for a longer period.
• Approximately 1/4 of the study participants didn’t comply with the supplementation guidelines, and were thus excluded from the study results.

What would really be interesting to learn going forward is what neuroprotective effects may be offered by more balanced forms of vitamin E given to younger participants in moderate amounts and with meals containing fat. Such an interventional study would obviously take many years to perform in humans. Animal (e.g., mice) studies, although less conclusive, could be performed in the near-term.

Hopefully we’ll continue to see research done in this area, as early intervention is likely the best bet for heading off the progression of cognitive decline into more severe conditions such as Alzheimer’s disease.

A recent study in the Journal of Gerontology took a look at the potential protective effect of beta-carotene in people with Alzheimer’s disease (AD). The researchers found that those individuals with a specific genotype known to be associated with greater risk of developing AD had a significantly reduced risk of cognitive decline if serum beta-carotene levels were kept high.

Earlier studies have identified that people who have blood lipoproteins of the apoE4 genetic type are at greater risk of developing early-onset AD. Lipoproteins are molecules that help transport fats and cholesterol through the blood. There are three types of these particular lipoproteins: apoE2, apoE3, and apoE4.

Each person has two copies of the gene that codes for this lipoprotein, one from the mother and one from the father. If both copies of the gene code for apoE4, then one is considered homozygous for that trait. If only one of the parents’ genes code for it, then one is considered heterozygous for that trait. Those at highest risk are individuals who are homozygous for apoE4.

More on the different gene types here:

• ApoE4 is associated with a higher risk of Alzheimer’s. About a quarter of the population inherits one copy of the ApoE4 gene, which increases their risk of developing Alzheimer’s disease by up to four times.
• Two per cent of the population get a ‘double dose’ of the ApoE4 gene, one from each parent. Their risk of developing Alzheimer’s disease is increased by about ten times.
• Sixty per cent of the population have a ‘double dose’ of the ApoE3 gene and are at ‘average risk’. About half of this group develop Alzheimer’s disease by their late 80s.
• ApoE2 is least associated with Alzheimer’s disease. One in six people carry it. People with one ApoE2 gene and one ApoE3 gene (11 per cent of the population) have a 50 per cent chance of getting Alzheimer’s disease when they reach their late 90s.
• One in 200 people inherit two copies of the ApoE2 gene and are at a lower risk of developing Alzheimer’s disease.

The researchers in the beta-carotene study found that in those individuals who were either hetero- or homozygous for apoE4, high serum levels of beta-carotene reduced the risk of cognitive decline by 89%. Little effect (11% risk reduction) was observed in people with no apoE4.

The researchers hypothesize that the beta-carotene may help to reduce the oxidative stress and resulting tissue damage that is observed with the build-up of beta-amyloid plaque deposits in AD brains. Also, there is research that suggests that people with the apoE4 form of the gene are less able to prevent the buildup of the plaque deposits observed in AD.

Another hypothesis as to why people with apoE4 are at higher risk is that a primary difference between the three lipoprotein types is the number of cysteine amino acids in the lipoprotein’s amino acid chain. apoE2 has two cysteine amino acids, apoE3 has one, and apoE4 has none. Cysteine is a sulfur-containing amino acid. Mercury has a high affinity for sulfur. The absence of cysteine in the apoE4 form of the lipoprotein may make individuals with this form less able to remove heavy metals from the bloodstream and more susceptible to toxin exposure.

Regardless of the mechanism, antioxidants such as beta-carotene, seem to play an important role in helping to manage the oxidative stress observed in AD.